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Examining the Level of Knowledge of Teachers About Asthma, Diabetes and Epilepsy in Children: A Systematic Review
No full textBackground/Objectives: Asthma, type 1 diabetes mellitus (T1DM), and epilepsy are prevalent chronic diseases among school-aged children, affecting safety, attendance, and academic performance. This systematic review evaluated school teachers’ knowledge, attitudes, and preparedness regarding these conditions and identified gaps that hinder effective management and inclusion. Methods: Following PRISMA guidelines, PubMed, Cochrane Library, Scopus, and Google Scholar were searched between 20 September and 9 October 2025. Forty-nine quantitative cross-sectional studies assessing teachers’ knowledge, attitudes, or preparedness toward asthma, T1DM, or epilepsy were included. The AXIS tool assessed methodological quality, focusing on clarity of objectives, sample justification, ethical transparency, and instrument validation. Results: Teachers’ knowledge was generally moderate and varied by region. Studies on epilepsy (n = 21) highlighted misconceptions and limited understanding of seizure first aid. Diabetes studies (n = 9) indicated moderate awareness but insufficient preparedness for hypoglycemia and insulin management. Asthma studies (n = 19) revealed inconsistent knowledge, particularly regarding symptom recognition and emergency response. AXIS assessment identified recurring limitations, including unjustified sample sizes, limited instrument validation, and poor reporting of non-responders. Conclusions: These findings emphasize the need to enhance school preparedness through targeted, evidence-based teacher training, clear health policies and emergency protocols, awareness and inclusion initiatives, improved collaboration among teachers, parents, and healthcare providers, and strengthened school health infrastructure. Addressing these areas is critical to ensure safe, inclusive, and supportive learning environments for children with chronic illnesses
Perceived stress four weeks after initiation of escitalopram monotherapy as a predictor of anxiolytic and antidepressant effects
No full textBackground Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for depression and anxiety, yet response rates remain suboptimal. Clinically accessible predictors of treatment outcome are therefore needed to guide decision-making in routine care. Methods In this analysis, we examined data from a prospective hospital-based cohort of 92 outpatients with depression who initiated escitalopram monotherapy guided by therapeutic drug monitoring. The objective was to determine whether early levels of perceived stress predict subsequent treatment outcomes. Psychometric assessments included the clinician-rated Hamilton Depression (HAMD) and Anxiety (HAMA) Rating Scales and the self-rated Perceived Stress Scale (PSS), collected at baseline, week four, and week eight. Treatment outcomes were defined as absolute and relative changes in HAMD and HAMA scores at week eight, as well as response (≥50% HAMD reduction) and remission (HAMD 25), where remission was rare (1/21). The week-4 PSS score was also associated with improvement in anxiety symptoms, although less robust after adjustment for concurrent anxiety severity. Conclusion Early perceived stress may represent a promising and accessible predictor of SSRI treatment outcomes. As an exploratory analysis, these findings should be considered hypothesis-generating and require replication before clinical implementation. The PSS is adaptable for digital platforms and may support future remote monitoring
In Vitro Pharmacokinetic Profiling of Thiourea Derivatives of Naproxen With Anti-Inflammatory and Anticancer Activity
No full textPharmacokinetic deficiencies account for nearly 40% of clinical drug candidate failures, emphasising the importance of early in vitro evaluation. Following the 3Rs principle, this study assessed the in vitro pharmacokinetic properties of thiourea derivatives of naproxen (1–14). Permeability assessment using the parallel artificial membrane permeability assay method revealed that derivatives 4 (-logPe = 4.13, p = 0.0859) and 7 (-logPe = 3.94, p = 0.2291) exhibited the highest passive gastrointestinal absorption potential, comparable to naproxen. Evaluation of binding affinity to human serum albumin (HSA) using the high-performance affinity chromatography method identified two groups of compounds: high-binding aromatic amine derivatives (except derivative 5) and low-binding aromatic amino acid ester derivatives. Microsomal stability assays indicated that compound 7 underwent the most extensive metabolic degradation (65.83% decrease). These findings suggest that further structural optimisation of compound 7, such as esterification with higher or branched alcohols, should lead to the improvement of HSA binding and reduction of metabolic susceptibility. Conversely, compound 4 combines favorable biological activity with a pharmacokinetic profile closely resembling that of naproxen. Although limited by the exclusive use of in vitro models and the absence of in vivo validation, this study provides valuable insights for the rational design of naproxen-based thiourea derivatives with enhanced anti-inflammatory and anticancer potential
The effects of Lactobacillus and/ or Bifidobacterium in fermented foods on cognitive health: a systematic review
No full textBackground: Psychobiotics are microorganisms that modulate brain functionvia the gut–brain axis and are increasingly studied for their cognitive benefits.Lactobacillus and Bifidobacterium species, widely present in fermentedfoods, are considered safe and may influence cognition by modulatingneuroinflammation, neurotransmitters, and gut barrier integrity. This systematicreview examined the effects of foods fermented with these species on cognitiveperformance in healthy adults and individuals with mild cognitive impairment.Methods: We conducted the systematic review following EFSA guidelines,Cochrane methodology, and a PROSPERO protocol, using CADIMA for study selection and data extraction. PubMed, Scopus, and Cochrane Library were searched (1 January 1970–31 August 2023) for human intervention and observational studies assessing cognitive outcomes after ingestion of foods fermented with Lactobacillus or Bifidobacterium. Eligible populations included healthy adults and individuals with mild cognitive impairment; studies involving disease were excluded. Screening, data extraction, and bias assessment followed Muka et al.’s 24-step guide using ROBINS and Cochrane/CADIMA frameworks. Evidence was synthesized narratively, while a non-systematic component examined food characteristics, potential mechanisms, and factors affecting bioavailability of bioactive constituents.Results: We included 21 studies (8 interventional, 13 observational). The majority of studies reported benefits, particularly in episodic memory, executive functions, and global cognition, but evidence was limited by inadequate controls, small sample sizes, short interventions, inconsistent domain assessment, and incomplete food characterization. Observational studies had larger populations and longer follow-ups but were limited by exposure assessment and depth of cognitive testing.Conclusion: Consumption of foods fermented with Lactobacillus and/or Bifidobacterium species may offer promising cognitive benefits. However, following EFSA’s guidance on the substantiation of health claims, the current evidence is “neither convincing nor sufficient” to establish a causal relationship. Well-designed studies with thorough product characterization are needed to substantiate effects and support potential health claims.Systematic review registration: This study was registered at the Open Science Framework (10.17605/OSF.IO/Z6GRW)
3D printed extended-release hydrochlorothiazide tablets
No full textIn this study 3D printed tablets (printlets) with extended release of hydrochlorothiazide (HHT) as model active
ingredient were designed and developed. Four formulations, F0.1SSE, F1SSE, F0.1DLP and F1DLP, have been
manufactured and characterized, using non-typical semi-solid extrusion (SSE) with UV light solidification and
digital light processing (DLP) techniques. Obtained rheological studies pointed out to F1SSE and F1DLP as more
suitable for SSE and DLP printing, respectively. Photopolymerization process between photopolymer (PEGDA)
and photoinitiator (DPPO; 0.1% and 1%) was investigated using FTIR, with PCA modeling utilized to analyze
spectral variations over time and estimate crosslinking kinetics. SSE printlets averaged ~6.5 mm in diameter, ~3
mm in height and ~110 mg in mass, while DLP printlets averaged ~8.5 mm in diameter, ~2.5 mm in height,
with masses of ~170 mg (F0.1DLP) and ~220 mg (F1DLP). All four formulations complied to the requirements of
European pharmacopeia for uniformity of dosage units of single dose preparations. In vitro release studies
indicated extended-release profiles in both 0.1M Hydrochloric acid (HCl) and phosphate buffer pH 6.8 for SSE
and DLP printlets. The release kinetics of HHT from the printlets were modeled to fit First order, Higuchi,
Korsmeyer-Peppas and Hixson-Crowell equations and the most probable ones were determined based on the R2
values and Akaike information criterion. FTIR and Raman spectroscopic analyses of printlets confirmed the
presence of characteristic peaks from both, HHT and excipients, as well as modifications in bonds due to the
photopolymeric reaction
Selective Laser Sintering 3D Printing of Carvedilol Tablets: Enhancing Dissolution Through Amorphization
No full textBackground/Objectives: Selective laser sintering (SLS) is one of the most promising 3D printing techniques for pharmaceutical applications as it offers numerous advantages, such as suitability to work with already approved pharmaceutical excipients, the elimination of solvents, and the ability to produce fast-dissolving, porous dosage forms with high drug loading. When the powder mixture is exposed to elevated temperatures during SLS printing, the active ingredients can be converted from the crystalline to the amorphous state, which can be used as a strategy to improve the dissolution rate and bioavailability of poorly soluble drugs. This study investigates the potential application of SLS 3D printing for the fabrication of tablets containing the poorly soluble drug carvedilol with the aim of improving the dissolution rate of the drug by forming an amorphous form through the printing process. Methods: Using SLS 3D printing, eight tablet formulations were produced using two different powder mixtures and four combinations of experimental conditions, followed by physicochemical characterization and dissolution testing. Results: Physicochemical characterization revealed that at least partial amorphization of carvedilol occurred during the printing process. Although variations in process parameters were minimal, higher temperatures in combination with lower laser speeds appeared to facilitate a greater degree of amorphization. Ultimately, the partial conversion to the amorphous form significantly improved the dissolution of carvedilol compared to its pure crystalline form. Conclusions: Obtained results suggest that the SLS 3D printing technique can be effectively used to convert poorly water-soluble drugs to their amorphous state, thereby improving solubility and bioavailability
Bioactivity Assessment of Functionalized TiO2 Powder with Dihydroquercetin
No full textBiological activities, including cell viability, oxidative stress, genotoxicity/antigenotoxicity, and antimicrobial activity, were evaluated for a visible-light-responsive TiO2-based ICT complex with dihydroquercetin (DHQ) and compared with pristine TiO2, its inorganic component. Pristine TiO2 did not induce cytotoxicity in MRC-5 or HeLa cells within the tested concentration range (1–20 mg/mL), while TiO2/DHQ displayed a significant reduction in cell viability in both cell lines at higher concentrations (≥10 mg/mL). The analysis of reactive oxygen species (ROS) production revealed that TiO2/DHQ significantly reduced ROS levels in both cell types (MRC-5 and HeLa), with HeLa cells showing a more substantial reduction at lower concentrations. Genotoxicity assessment using the comet assay demonstrated that TiO2 induced DNA damage in MRC-5 cells, while TiO2/DHQ did not, indicating that DHQ mitigates the genotoxic potential of TiO2. Furthermore, TiO2/DHQ exhibited antigenotoxic effects by reducing H2O2-induced DNA damage in MRC-5 cells, supporting its protective role against oxidative stress. Preliminary antimicrobial tests revealed that TiO2/DHQ exhibits antimicrobial activity against E. coli under visible-light excitation, while TiO2 does not. These findings suggest that the TiO2-based ICT complex with DHQ with enhanced antioxidant properties can potentially serve as a safe, non-toxic biocide agent
Intravenous Nanoemulsions Loaded with Phospholipid Complex of a Novel Pyrazoloquinolinone Ligand for Enhanced Brain Delivery
No full textBackground/Objectives: The novel pyrazoloquinolinone ligand CW-02-79 shows a unique profile of selective binding to σ2 receptors, but its poor solubility in both water and lipids makes its research and development a burdensome task. We aimed to develop a phospholipid-complex-based nanoemulsion formulation containing CW-02-79 suitable for intravenous administration in preclinical research. Methods: The decorated and undecorated nanoemulsions were formulated and subjected to detailed physiochemical characterization. The delivery and exposure to CW-02-79 from selected nanoemulsions were examined in the in vitro blood–brain barrier model based on human-induced pluripotent stem-cell-derived microvascular endothelial cells, astrocytes, and pericytes, and in vivo neuropharmacokinetic study in rats, respectively. Results: The developed biocompatible nanoemulsions loaded with a CW-02-79—phospholipid complex at a mass ratio of 1:10 exhibited a small droplet size and narrow size distribution, with satisfactory physicochemical stability during steam sterilization and short-term storage at 25 °C. The analysis of protein binding interactions revealed that the PEGylated nanoemulsions had fewer observable interactions compared to the undecorated nanoemulsions, especially when 0.2% DSPE-PEG2000 and 0.1% DSPE-PEG2000-mannose were combined. An in vitro BBB study demonstrated that a substantial part of CW-02-79 present in the applied nanoemulsion is able to permeate the barrier. The quantification of CW-02-79 in plasma/brain homogenate and calculated pharmacokinetic parameters confirmed good systemic and brain availability after intravenous administration. There were subtle differences in the pharmacokinetic parameters in favor of a dual surface-functionalized nanoemulson containing the glucose transporter-1-targeting ligand (mannose). Conclusions: The developed and characterized nanoemulsions enable substantial brain exposure to CW-02-79 as a prerequisite for a pharmacologically and clinically relevant selective modulation of σ2 receptors
Comparative in silico/in vitro analysis of pharmacokinetic profiles of BET inhibitors
No full textPharmacokinetic limitations are a common cause of drug development failure, making early-stage profiling essential to mitigate financial risks and guide compound optimization. The computational tools capable of predicting pharmacokinetic properties offer a valuable resource for the prioritizing of candidates during early discovery phases. This study provides a comparative analysis of in silico and in vitro pharmacokinetic profiles of bromodomain and extraterminal domain (BET) inhibitors (BIs), focusing on sixteen (+)-JQ1-derived compounds we previously synthesized. Using ADMETlab 2.0 software, we predicted key absorption, distribution, metabolism, and excretion (ADME) parameters and compared them with experimentally determined data. Strong correlations were observed for plasma protein binding, whereas notable discrepancies were identified in permeability and clearance values. Additionally, the analysis underscores the role of CYP3A4 as a critical enzyme in the metabolism of several BIs. These findings demonstrate the utility of computational tools like ADMETlab 2.0 for early pharmacokinetic profiling while highlighting the need for validation and refinement of predictive models. This work provides valuable insights into the pharmacokinetics of BIs and supports the integration of computational and experimental approaches in drug discovery
Chemometric modeling for blood–brain-barrier permeability prediction of protein kinase inhibitors
No full textLimited passage through the blood-brain barrier (BBB) poses a major challenge in
developing therapeutics for the central nervous system (CNS), especially for protein kinase
inhibitors, which have high potential for treating different neurological disorders and
malignancies. This study investigates the passive permeability of 34 diverse compounds,
comprising both approved protein kinase inhibitors and experimental compounds, using the
parallel artificial membrane permeability assay (PAMPA-BBB). Quantitative structure-property
relationship (QSPR) models were developed utilizing Multiple Linear Regression (MLR), Support
Vector Machine Regression (SVM), and Artificial Neural Networks (ANN). These models
employed molecular descriptors of the compounds to create predictive models for assessing the
permeability of other compounds. The study found that among the molecular descriptors,
CATS2D_04_AA had the strongest positive correlation with logPe, indicating enhanced BBB
permeability, while CATS2D_09_DA negatively impacted permeability. Both linear (MLR) and
nonlinear (ANN and SVM) models confirmed these relationships, with the SVM model showing
better performance due to capturing nonlinear dependencies, particularly for descriptors like
CATS2D_04_AA and F07[C-N]. Optimizing structural features, including reducing hydrogen
bond donors, was proposed to improve BBB permeability, thus offering guidance for the design
of kinase inhibitors with improved CNS delivery potential. The integration of PAMPA-BBB
assays with robust QSAR modeling provides a reliable framework for optimizing CNS-targeted
drug candidates