Search Results (16)

Background: Opioids remain the most effective component of systemic analgesia and are considered safe and beneficial when administered at the lowest effective dose. Nevertheless, their potential adverse effects may diminish the quality of the postoperative period or, in some cases, lead to life-threatening complications. This analysis examines whether the mandatory implementation of a standardised protocol offers opioid-sparing potential. Methods: In this single-centre retrospective cohort study, intraoperative opioid consumption during laparoscopic appendectomy was compared between patients anaesthetised according to a standardised protocol (n₁ = 132) and those managed at clinicians’ discretion in line with good medical practice (n₂ = 212). Length of hospital stay and use of intraoperative non-opioid analgesics were also assessed. Results: The total fentanyl dose administered during anaesthesia was significantly lower in the standardised protocol cohort compared to the cohort without a protocol: 3.13 μg·kg⁻¹ (IQR: 2.98–4.08) vs. 5.19 μg·kg⁻¹ (IQR: 3.89–6.67), p < 0.001. In the protocol cohort, the percentage of patients who received acetaminophen and metamizole was significantly higher—increasing by 57% and 23%, respectively (p < 0.001). No significant inter-cohort difference was observed in terms of length of hospital stay. Conclusions: The use of a mandatory anaesthetic protocol based on a multimodal approach had an opioid-sparing effect in children undergoing laparoscopic appendectomy. This retrospective analysis was approved by the Ethics Committee of the Medical University of Warsaw (identifier: AKBE/118/2025; date of acceptance: 12 May 2025), and the primary trial was registered in the U.S. National Library of Medicine Clinical Trials Registry (registration number: NCT05238506; date of first registration: 14 February 2022). Full article

Presbyopia is a global problem with an estimated 1.3 billion patients worldwide. In the area of functional food applications, dietary supplements or herbs, there are very few reports describing the positive effects of their use. In the available literature, there is a lack of studies in humans as well as on an animal model of extracts containing, simultaneously, compounds from the polyphenol group (in particular, anthocyanins) and iridoids, so we undertook a study of the effects of a preparation composed of these compounds on a condition of the organ of vision. Our previous experience on a rabbit model proved the positive effect of taking an oral extract of Cornus mas in stabilizing the intraocular pressure of the eye. The purpose of this study was to evaluate the effect of an orally administered ternary compound preparation on the status of physiological parameters of the ocular organ. The preparation contained an extract of the chokeberry Aronia melanocarpa, the honeysuckle berry Lonicera caerulea L., and the bilberry Vaccinium myrtillus (hereafter AKB) standardized for anthocyanins and iridoids, as bioactive compounds known from the literature. A randomized, double-blind, cross-over study lasting with a “wash-out” period of 17 weeks evaluated a group of 23 people over the age of 50, who were subjects with presbyopia and burdened by prolonged work in front of screen monitors. The group of volunteers was recruited from people who perform white-collar jobs on a daily basis. The effects of the test substances contained in the preparation on visual acuity for distance and near, sense of contrast for distance and near, intraocular pressure, and conjunctival lubrication, tested by Schirmer test, LIPCOF index and TBUT test, and visual field test were evaluated. Anthocyanins (including cyanidin 3-O-galactoside, delphinidin 3-O-arabinoside, cyanidin 3-O-glucoside, cyanidin 3-O-rutinoside, cyanidin 3-O-arabinoside) and iridoids (including loganin, sweroside, loganic acid) were identified as substances present in the extract obtained by HPLC-MS. The preliminary results showed that the composition of AKB applied orally does not change visual acuity in the first 6 weeks of administration. Only in the next cycle of the study was an improvement in near visual acuity observed in 92.3% of the patients. This may indicate potential to correct near vision in presbyopic patients. On the other hand, an improvement in conjunctival wetting was observed in the Schirmer test at the beginning of week 6 of administration in 80% of patients. This effect was weakened in subsequent weeks of conducting the experiment to 61.5%. The improvement in conjunctival hydration in the Schirmer test shows the potential beneficial effect of the AKB formulation in a group of patients with dry eye syndrome. This is the first study of a preparation based on natural, standardized extracts of chokeberry, honeysuckle berry, and bilberry. Preliminary studies show an improvement in near visual acuity and conjunctival hydration on the Schirmer test, but this needs to be confirmed in further studies. Full article

Multiple forms of interference and noise that impact the receiver’s capacity to receive and interpret satellite signals, and consequently the preciseness of positioning and navigation, may be present during the processing of Global Positioning System (GPS) navigation. The non-Gaussian noise predominates in the signal owing to the fluctuating character of both natural and artificial electromagnetic interference, and the algorithm based on the minimum mean-square error (MMSE) criterion performs well when assuming Gaussian noise, but drops when assuming non-Gaussian noise. The maximum correntropy criteria (MCC) adaptive filtering technique efficiently reduces pulse noise and has adequate performance in heavy-tailed noise, which addresses the issue of filter performance caused by the presence of non-Gaussian or heavy-tailed unusual noise values in the localizing measurement noise. The adaptive kernel bandwidth (AKB) technique employed in this paper applies the calculated adaptive variables to generate the kernel function matrix, in which the adaptive factor can modify the size of the kernel width across a reasonably appropriate spectrum, substituting the fixed kernel width for the conventional MCC to enhance the performance. The conventional maximum correntropy criterion-based extended Kalman filter (MCCEKF) algorithm’s performance is significantly impacted by the value of the kernel width, and there are certain predetermined conditions in the selection based on experience. The MCCEKF with a fixed adaptive kernel bandwidth (MCCEKF-AKB) has several advantages due to its novel concept and computational simplicity, and gives a qualitative solution for the study of random structures for generalized noise. Additionally, it can effectively achieve the robust state estimation of outliers with anomalous values while guaranteeing the accuracy of the filtering. Full article

(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as ‘K2’, ‘K9’ or ‘Spice’. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). Moreover, early cases of intoxication and death related to SCs highlight the inherent danger that may accompany the use of these substances. However, there is limited knowledge of the toxicology of Spice ingredients. This systematic review intends to analyze the toxicity of SCs compounds in Spice/K2 drugs. (2) Methods: Studies analyzing synthetic cannabinoid toxicity and dependence were included in the present review. We searched the PubMed database of the US National Library of Medicine, Google Scholar, CompTox Chemicals, and Web of Science up to May 2022. (3) Results: Sixty-four articles reporting the effects of synthetic cannabinoids in humans were included in our review. Ten original papers and fifty-four case studies were also included. Fourteen studies reported death associated with synthetic cannabinoid use, with AB-CHMINACA and MDMB-CHMICA being the main reported SCs. Tachycardia and seizures were the most common toxicity symptoms. The prevalence of neuropsychiatric symptoms was higher in third-generation SCs. (4) Conclusion: SCs may exhibit higher toxicity than THC and longer-lasting effects. Their use may be harmful, especially in people with epilepsy and schizophrenia, because of the increased risk of the precipitation of psychiatric and neurologic disorders. Compared to other drugs, SCs have a higher potential to trigger a convulsive crisis, a decline in consciousness, and hemodynamic changes. Therefore, it is crucial to clarify their potential harms and increase the availability of toxicology data in both clinical and research settings. Full article

The use of by-products from the agri-food industry is a promising approach for production of value-added, polyphenol-rich dietary supplements or natural pharmaceutical preparations. During pistachio nut processing, a great amount of husk is removed, leaving large biomass for potential re-use. The present study compares antiglycative, antioxidant, and antifungal activities as well as nutritional values of 12 genotypes belonging to four pistachio cultivars. Antioxidant activity was measured using DPPH and ABTS assays. Antiglycative activity was evaluated as inhibition of advanced glycation end product (AGE) formation in the bovine serum albumin/methylglyoxal model. HPLC analysis was performed to determine the major phenolic compounds. Cyanidin-3-O-galactoside (120.81–181.94 mg/100 g DW), gallic acid (27.89–45.25), catechin (7.2–11.01), and eriodictyol-7-O-glucoside (7.23–16.02) were the major components. Among genotypes, the highest total flavonol content (14.8 mg quercetin equivalents/g DW) and total phenolic content (262 mg tannic acid equivalent/g DW) were in KAL1 (Kaleghouchi) and FAN2 (Fandoghi), respectively. The highest antioxidant (EC₅₀ = 375 μg/mL) and anti-glycative activities were obtained for Fan1. Furthermore, potent inhibitory activity against Candida species was recorded with MIC values of 3.12–12.5 µg/mL. The oil content ranged from 5.4% in Fan2 to 7.6% in Akb1. The nutritional parameters of the tested cultivars were highly variable: crude protein (9.8–15.8%), ADF (acid detergent fiber 11.9–18.2%), NDF (neutral detergent fiber, 14.8–25.6%), and condensed tannins (1.74–2.86%). Finally, cyanidin-3-O-galactoside was considered an effective compound responsible for antioxidant and anti-glycative activities. Full article

Aurora kinase B (AKB) is a crucial signaling kinase with an important role in cell division. Therefore, inhibition of AKB is an attractive approach to the treatment of cancer. In the present work, extensive quantitative structure–activity relationships (QSAR) analysis has been performed using a set of 561 structurally diverse aurora kinase B inhibitors. The Organization for Economic Cooperation and Development (OECD) guidelines were used to develop a QSAR model that has high statistical performance (R²_tr = 0.815, Q²_LMO = 0.808, R²_ex = 0.814, CCC_ex = 0.899). The seven-variable-based newly developed QSAR model has an excellent balance of external predictive ability (Predictive QSAR) and mechanistic interpretation (Mechanistic QSAR). The QSAR analysis successfully identifies not only the visible pharmacophoric features but also the hidden features. The analysis indicates that the lipophilic and polar groups—especially the H-bond capable groups—must be present at a specific distance from each other. Moreover, the ring nitrogen and ring carbon atoms play important roles in determining the inhibitory activity for AKB. The analysis effectively captures reported as well as unreported pharmacophoric features. The results of the present analysis are also supported by the reported crystal structures of inhibitors bound to AKB. Full article

In 2019, synthetic cannabinoids accounted for more than one-third of new drugs of abuse worldwide; however, assessment of associated health risks is not ethical for controlled and often illegal substances, making CD-1 mouse exposure studies the gold standard. Interpretation of those findings then depends on the similarity of mouse and human metabolic pathways. Herein, we report the first comparative analysis of steady-state metabolism of N-(1-adamantyl)-1-(5-pentyl)-1H-indazole-3-carboxamide (5F-APINACA/5F-AKB48) in CD-1 mice and humans using hepatic microsomes. Regardless of species, 5F-APINACA metabolism involved highly efficient sequential adamantyl hydroxylation and oxidative defluorination pathways that competed equally. Secondary adamantyl hydroxylation was less efficient for mice. At low 5F-APINACA concentrations, initial rates were comparable between pathways, but at higher concentrations, adamantyl hydroxylations became less significant due to substrate inhibition likely involving an effector site. For humans, CYP3A4 dominated both metabolic pathways with minor contributions from CYP2C8, 2C19, and 2D6. For CD-1 mice, Cyp3a11 and Cyp2c37, Cyp2c50, and Cyp2c54 contributed equally to adamantyl hydroxylation, but Cyp3a11 was more efficient at oxidative defluorination than Cyp2c members. Taken together, the results of our in vitro steady-state study indicate a high conservation of 5F-APINACA metabolism between CD-1 mice and humans, but deviations can occur due to differences in P450s responsible for the associated reactions. Full article

The therapeutic potential of mesenchymal stromal cells (MSCs) is largely attributed to their immunomodulatory properties, which can be further improved by hypoxia priming. In this study, we investigated the immunomodulatory properties of MSCs preconditioned with hypoxia-mimetic Vadadustat (AKB-6548, Akebia). Gene expression analysis of immunomodulatory factors was performed by real-time polymerase chain reaction (real-time PCR) on RNA isolated from six human bone-marrow derived MSCs populations preconditioned for 6 h with 40 μM Vadadustat compared to control MSCs. The effect of Vadadustat preconditioning on MSCs secretome was determined using Proteome Profiler and Luminex, while their immunomodulatory activity was assessed by mixed lymphocyte reaction (MLR) and Culturex transwell migration assays. Real-time PCR revealed that Vadadustat downregulated genes related to immune system: IL24, IL1B, CXCL8, PDCD1LG1, PDCD1LG2, HIF1A, CCL2 and IL6, and upregulated IL17RD, CCL28 and LEP. Vadadustat caused a marked decrease in the secretion of IL6 (by 51%), HGF (by 47%), CCL7 (MCP3) (by 42%) and CXCL8 (by 40%). Vadadustat potentiated the inhibitory effect of MSCs on the proliferation of alloactivated human peripheral blood mononuclear cells (PBMCs), and reduced monocytes-enriched PBMCs chemotaxis towards the MSCs secretome. Preconditioning with Vadadustat may constitute a valuable approach to improve the therapeutic properties of MSCs. Full article

In 2020, nearly one-third of new drugs on the global market were synthetic cannabinoids including the drug of abuse N-(1-adamantyl)-1-(5-pentyl)-1H-indazole-3-carboxamide (5F-APINACA, 5F-AKB48). Knowledge of 5F-APINACA metabolism provides a critical mechanistic basis to interpret and predict abuser outcomes. Prior qualitative studies identified which metabolic processes occur but not the order and extent of them and often relied on problematic “semi-quantitative” mass spectroscopic (MS) approaches. We capitalized on 5F-APINACA absorbance for quantitation while leveraging MS to characterize metabolite structures for measuring 5F-APINACA steady-state kinetics. We demonstrated the reliability of absorbance and not MS for inferring metabolite levels. Human liver microsomal reactions yielded eight metabolites by MS but only five by absorbance. Subsequent kinetic studies on primary and secondary metabolites revealed highly efficient mono- and dihydroxylation of the adamantyl group and much less efficient oxidative defluorination at the N-pentyl terminus. Based on regiospecificity and kinetics, we constructed pathways for competing and intersecting steps in 5F-APINACA metabolism. Overall efficiency for adamantyl oxidation was 17-fold higher than that for oxidative defluorination, showing significant bias in metabolic flux and subsequent metabolite profile compositions. Lastly, our analytical approach provides a powerful new strategy to more accurately assess metabolic kinetics for other understudied synthetic cannabinoids possessing the indazole chromophore. Full article

The proliferation of residential building energy consumption and CO₂ emissions has led many countries to develop buildings under the green rating systems umbrella. Many such buildings, however, fail to meet their designed energy performance, which is possibly attributable to occupant behaviour and unforeseen building usages. The research problem lies in the fact that occupant environmental behaviour is a complex socio-cultural-technical issue that needs to be addressed to achieve the desired energy savings. This study is novel as it investigates complex interrelationships between many observed and unobserved variables using data from four LEED-certified multi-residential buildings in the United Arab Emirates. Structural Equation Modelling was used to analyse the impact of three unobserved/latent variables: occupant environmental Attitude, Knowledge and Behaviour (AKB) with respect to occupant energy consumption, based on measured/observed variables. Although our Goodness-of-Fit values indicated that we achieved a good model fit, the interrelationship between Knowledge and Behaviour (p = 0.557) and between Attitude and Behaviour (p = 0.931) was insignificant, as the p-values > 0.05. The key study outcomes were: (i) providing information alone could not motivate people towards environmentally friendly behaviour; (ii) even changes in their attitude, belief and lifestyle were not significantly related to their behaviour, as the interrelationships among occupant environmental AKB were not significant; and (iii) knowledge and attitude change should be combined with other motivational factors to trigger environmentally friendly actions and influence behaviour. Full article

Novel Psychoactive Substances (NPS) include several classes of substances such as synthetic cannabinoids (SCBs), an emerging alternative to marijuana, easily purchasable on internet. SCBs are more dangerous than Δ⁹-Tetrahydrocannabinol as a consequence of their stronger affinities for the CB₁ and CB₂ receptors, which may result in longer duration of distinct effects, greater potency, and toxicity. The information on SCBs cytotoxicity, genotoxicity, mutagenicity, and long-term effects is scarce. This fact suggests the urgent need to increase available data and to investigate if some SCBs have an impact on the stability of genetic material. Therefore, the aim of the present study was the evaluation of the mutagenic effect of different SCBs belonging to indole- and indazole-structures. The analyzes were conducted in vitro on human TK6 cells and mutagenicity were measured as micronucleus fold increase by flow cytometry. Our results have highlighted, for the first time, the mutagenic capacity of four SCBs, in particular in terms of chromosomal damage induction. We underline the serious potential toxicity of SCBs that suggests the need to proceed with the studies of other different synthetic compounds. Moreover, we identified a method that allows a rapid but effective screening of NPS placed on the market increasingly faster. Full article

APINACA (known as AKB48, N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide), an indazole carboxamide synthetic cannabinoid, has been used worldwide as a new psychoactive substance. Drug abusers take various drugs concomitantly, and therefore, it is necessary to characterize the potential of APINACA-induced drug–drug interactions due to the modulation of drug-metabolizing enzymes and transporters. In this study, the inhibitory effects of APINACA on eight major human cytochrome P450s (CYPs) and six uridine 5′-diphospho-glucuronosyltransferases (UGTs) in human liver microsomes, as well as on the transport activities of six solute carrier transporters and two efflux transporters in transporter-overexpressed cells, were investigated. APINACA exhibited time-dependent inhibition of CYP3A4-mediated midazolam 1′-hydroxylation (K_i, 4.5 µM; k_inact, 0.04686 min⁻¹) and noncompetitive inhibition of UGT1A9-mediated mycophenolic acid glucuronidation (K_i, 5.9 µM). APINACA did not significantly inhibit the CYPs 1A2, 2A6, 2B6, 2C8/9/19, or 2D6 or the UGTs 1A1, 1A3, 1A4, 1A6, or 2B7 at concentrations up to 100 µM. APINACA did not significantly inhibit the transport activities of organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, organic cation transporter (OCT)1, OCT2, P-glycoprotein, or breast cancer resistance protein at concentrations up to 250 μM. These data suggest that APINACA can cause drug interactions in the clinic via the inhibition of CYP3A4 or UGT1A9 activities. Full article

In this study, carbonized kelp biochar (AKB) modified by KOH impregnation and photocatalytic Bi₂MoO₆/AKB composite (BKBC) nanomaterials were the first time successfully synthesized for efficient removal of dyes in aqueous solution. BET, XRD, FT-IR, and SEM were employed to characterize as-prepared samples. UV-vis and other test results indicated that the removal efficiency of methylene blue (MB) was 61.39% and 94.12% for BKBC and AKB, respectively, which was up to 13 times and 20 times higher in comparison with pure Bi₂MoO₆ (PBM). In addition, the equilibrium adsorption capacity of MB could reach up to 324.1 mg/g for AKB. This high dyes adsorption performance could be likely attributed to its high specific surface area (507.177 m²/g) and its abundant presence of various functional groups such as –OH and =C–H on AKB. Particularly, the existing of amorphous carbon and transition metal oxides, such as Fe₂O₃ and Mn₅O₈, could be beneficial for the photodegradation of MB for AKB. Meanwhile, experimental data indicated that adsorption kinetics complied with the pseudo-second order model well, and all of the tests had satisfactory results in terms of the highly efficient adsorption and photodegradation activity of AKB nanomaterials, which suggested its great potential in wastewater treatment. Full article

Aurora kinases (AKs) are serine/threonine kinases that are essential for cell division. Humans have three AK genes: AKA, AKB, and AKC. AKA is required for centrosome assembly, centrosome separation, and bipolar spindle assembly, and its mutation leads to abnormal spindle morphology. AKB is required for the spindle checkpoint and proper cytokinesis, and mutations cause chromosome misalignment and cytokinesis failure. AKC is expressed in germ cells, and has a role in meiosis analogous to that of AKB in mitosis. Mutation of any of the three isoforms can lead to cancer. AK proteins possess divergent N- and C-termini and a conserved central catalytic domain. We examined the evolution of the AK gene family using an identity matrix and by building a phylogenetic tree. The data suggest that AKA is the vertebrate ancestral gene, and that AKB and AKC resulted from gene duplication in placental mammals. In a nonsynonymous/synonymous rate substitution analysis, we found that AKB experienced the strongest, and AKC the weakest, purifying selection. Both the N- and C-termini and regions within the kinase domain experienced differential selection among the AK isoforms. These differentially selected sequences may be important for species specificity and isoform specificity, and are therefore potential therapeutic targets. Full article

Hydrolysis of cellulose and hemicelluloses into fermentable sugars is the primary step for the production of fuels and chemicals from lignocellulosic biomass, and is often hindered by the high cost of cellulolytic and hemicellulolytic enzymes. In the present study co- and monocultures of Penicillium sp. AKB-24 and Aspergillus nidulans AKB-25 were used under a variety of fermentation conditions to optimize enzyme production. Wheat bran was found to be the optimal carbon source yielding maximum enzyme production under solid-state fermentation conditions due to its higher water retention value (175%) and minimum C/N ratio (22.7). Penicillium sp. AKB-24 produced maximum endoglucanase (134 IU/gds), FPase (3 FPU/gds), β-glucosidase (6 IU/gds) and xylanase (3592 IU/gds) activities when incubated for 7 days at 30 °C and pH 7 with a moisture content of 77.5%, and 1.2% yeast extract and 0.1 (w/v) sodium dodecyl sulphate supplement. Co-culturing of Penicillium sp. AKB-24 and Aspergillus nidulans AKB-25 enhanced endoglucanase, FPase, and exoglucanase activities by 34%, 18%, and 11% respectively compared to Aspergillus nidulans AKB-25 alone under optimum conditions. Enzymes produced by co-cultivation released equal amounts of reducing sugars at an enzyme dose of 15 FPU/g and reaction time 72 h, but the required quantity of enzyme was 14% less compared to enzyme released from Aspergillus nidulans AKB-25 mono-culture. In conclusion, co-cultivation of Penicillium sp. AKB-24 and Aspergillus nidulans AKB-25 to produce enzymes for the hydrolysis of pearl millet stover is more cost-effective than cultivation with Aspergillus nidulans AKB-25 alone. Full article