Although miRNA-27a has been identified as a promising candidate for miRNA mimic therapy of obesity, its application is limited due to enzymatic degradation and low membrane permeation. To overcome these problems, we developed cationic nanostructured lipid carriers (cNLCs) using high-pressure homogenization and used them as non-viral carriers for the anti-adipogenic miRNA-27a. Cargo-free octadecylamine-containing NLCs and miRNA/cNLC complexes were characterized regarding particle size, size distributions, zeta potential, pH values, particle topography and morphology, and entrapment efficacy. Furthermore, the cytotoxicity and cellular uptake of the miRNA/cNLC complex in the 3T3-L1 cell line were investigated. The investigation of the biological effect of miRNA-27a on adipocyte development and an estimation of the accumulated Oil-Red-O (ORO) dye in lipid droplets in mature adipocytes were assessed with light microscopy and absorbance measurements. The obtained data show that cNLCs represent a suitable DDS for miRNAs, as miRNA/cNLC particles are rapidly formed through non-covalent complexation due to electrostatic interactions between both components. The miRNA-27a/cNLC complex induced an anti-adipogenic effect on miRNA-27a by reducing lipid droplet accumulation in mature adipocytes, indicating that this approach might be used as a new therapeutic strategy for miRNA mimic replacement therapies in the prevention or treatment of obesity and obesity-related disorders.

Premature babies and those born with a medical condition are cared for within the neonatal intensive care unit (NICU) in hospitals. Monitoring physiological signals and subsequent analysis and interpretation can reveal acute and chronic conditions for these neonates. Several advanced algorithms using physiological signals have been built into existing monitoring systems to allow clinicians to analyse signals in real time and anticipate patient deterioration. However, limited enhancements have been made to interactively visualise and adapt them to neonatal monitoring systems. To bridge this gap, we describe the development of a user-friendly and interactive dashboard for neonatal vital signs analysis written in the Python programming language where the analysis can be performed without prior computing knowledge. To ensure practicality, the dashboard was designed in consultation with a neonatologist to visualise electrocardiogram, heart rate, respiratory rate and oxygen saturation data in a time-series format. The resulting dashboard included interactive visualisations, advanced electrocardiogram analysis and statistical analysis which can be used to extract important information on patients’ conditions.Clinical Relevance— This will support the care of preterm infants by allowing clinicians to visualise and interpret physiological data in greater granularity, aiding in patient monitoring and detection of adverse conditions. The detection of adverse conditions could allow timely and potentially life-saving interventions for conditions such as sepsis and brain injury.

Gravity inversions have contributed greatly to our knowledge of the interior of planetary bodies and the processes that shaped them. However, previous global gravity inversion methods neglect the inference of mantle density anomalies when using techniques to decrease the non‐uniqueness of the inversion. In this work, we present a novel global gravity inversion algorithm, named THeBOOGIe, suited to inferring global‐scale density anomalies within the crust and mantle of planetary bodies. The algorithm embraces the nonuniqueness inherent in gravity inversions by not prescribing at the outset a density interface or depth range of interest. Instead, the method combines a Bayesian approach with a flexible incorporation of prior geological or geophysical information to infer density anomalies at any depth. A validation test using synthetic lunar‐like gravity data shows that THeBOOGIe can constrain the lateral location of crustal density anomalies but tends to overestimate their thicknesses. Importantly, THeBOOGIe can detect deep mantle density anomalies and quantify the level of confidence in the inferred density models. Our results show that THeBOOGIe can provide complementary information to one‐dimensional seismic models of the interior of the terrestrial planets and the Moon by constraining density anomalies that are not spherically symmetric. Additionally, THeBOOGIe is specially suited to constraining the interior of partially differentiated bodies where these large‐scale density anomalies are more likely to exist. Finally, thanks to the flexible use of priors, THeBOOGIe is an essential tool to understand the interior of planetary bodies lacking additional constraints.

Small cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid proliferation, early dissemination, acquired therapy resistance, and poor prognosis. Early diagnosis of SCLC is crucial since most patients present with advanced/metastatic disease, limiting the potential for curative treatment. While SCLC exhibits initial responsiveness to chemotherapy and radiotherapy, treatment resistance commonly emerges, leading to a five-year overall survival rate of up to 10%. New effective biomarkers, early detection, and advancements in therapeutic strategies are crucial for improving survival rates and reducing the impact of this devastating disease. This review aims to comprehensively summarize current knowledge on diagnostic options, well-known and emerging biomarkers, and SCLC treatment strategies and discuss future perspectives on this aggressive malignancy.

Helichrysum italicum (Roth) G. Don., immortelle, is a plant species used in ethnomedicine and the food industry as a spice added to food, beverages, and bakery products. It has been shown to possess various biological activities, such as antioxidant and antibacterial activity, making it useful as a natural preservative. We investigated the phytochemical profile and biological activity of H. italicum essential oils from wild-grown plant material collected from natural habitats in the Republic of Croatia and Bosnia and Herzegovina. Using high-resolution scanning electron microscopy (SEM), a visual investigation of plant organs (stem, leaf, and flower) was performed, confirming the presence of essential oil reservoirs on the surface of all examined plant organs. Essential oils were isolated by hydrodistillation in the Clevenger apparatus. The chemical composition of the essential oils was determined using the GC-MS analytical technique. Cytotoxic activity tests were performed in vitro on three cell lines: skin (fibroblast), lung, and breast cancer. Using statistical tools, the synergistic and selective effects of H. italicum essential oil on healthy and tumor cells were correlated to chemical composition and cytotoxic activity. The synergistic and antagonistic effects of H. italicum essential oil’s individual components were simulated by testing pure compounds and their mixture of cytotoxic activity on fibroblasts and breast cancer cells. The results confirm that essential oil’s biological activity is much greater than the sum of the effects of its components. The present data are novel contributions to the body of knowledge on the biological activity of this species used in the food industry.

The aim of this paper is to highlight the importance of a multidimensional approach to the contextual assessment of learning abilities in students with cerebral palsy. The paper presents a case study of a nine-year-old student with multiple developmental disabilities (cerebral palsy and additional influencing difficulties) attending a regular primary school with an individual educational program (IEP). In order to determine the measures for individualizing the educational process for the student, the assessment of internal conditions and learning abilities was conducted individually within a daily rehabilitation center, while the environmental conditions were observed within the school setting. The evaluation of the assessment results emphasized the significance of conducting assessments in all relevant contexts, as it was the only way to obtain a comprehensive understanding of the student's level of functioning and the necessary measures for improving her learning and participation.Key words: multidimensional assessment, learning abilities, cerebral palsy

The main goal of the paper is to examine comprehension of basic emotion and facial expression of children with hearing impairment. The research encompasses a sample of 66 respondents out of which 33 have non-damaged hearing and the remaining 33 respondents have hearing impairment. The age of respondents ranges, in chronological order, from 7 to 15 years. Recognition of emotions and facial expressions is being examined through 4 sets of tasks. The Emotion Recognition Test (ERT) is being used for evaluation, it has been adapted for the purpose of this paper and thereby adjusted for electronic usage via computer and internet. Through statistical processing of given data, following components have been calculated: minimal and maximum values, arithmetic mean, standard deviation, Wilcoxon Signed Ranks Test, Mann-Whitney U test, curvature test and flattening of distribution curve, t-test. Research results concluded that hearing impairment in children affects, with statistical significance, recognition and comprehension of facial expressions and emotions compared to their peers with no hearing impairment. The results were expected given the hearing condition and the consequences which hearing impairment creates. Children with hearing impairment possess poor vocabulary which affects comprehension of emotions. Statistically significant difference occurs among children with hearing impairments and recognition and comprehension of facial expression and emotions within situational context and isolated facial expressions.Key words: deaf children, comprehension of emotions, emotions of the deaf, facial expressions, hearing impairments.

OP-145 and SAAP-148, two 24-mer antimicrobial peptides derived from human cathelicidin LL-37, exhibit killing efficacy against both Gram-positive and Gram-negative bacteria at comparable peptide concentrations. However, when it comes to the killing activity against Escherichia coli, the extent of membrane permeabilization does not align with the observed bactericidal activity. This is the case in living bacteria as well as in model membranes mimicking the E. coli cytoplasmic membrane (CM). In order to understand the killing activity of both peptides on a molecular basis, here we studied their mode of action, employing a combination of microbiological and biophysical techniques including differential scanning calorimetry (DSC), zeta potential measurements, and spectroscopic analyses. Various membrane dyes were utilized to monitor the impact of the peptides on bacterial and model membranes. Our findings unveiled distinct binding patterns of the peptides to the bacterial surface and differential permeabilization of the E. coli CM, depending on the smooth or rough/deep-rough lipopolysaccharide (LPS) phenotypes of E. coli strains. Interestingly, the antimicrobial activity and membrane depolarization were not significantly different in the different LPS phenotypes investigated, suggesting a general mechanism that is independent of LPS. Although the peptides exhibited limited permeabilization of E. coli membranes, DSC studies conducted on a mixture of synthetic phosphatidylglycerol/phosphatidylethanolamine/cardiolipin, which mimics the CM of Gram-negative bacteria, clearly demonstrated disruption of lipid chain packing. From these experiments, we conclude that depolarization of the CM and alterations in lipid packing plays a crucial role in the peptides’ bactericidal activity.