John Paul II Catholic University of Lublin

˃100 μM). The active substances (ASs) were successfully entrapped within alginate hydrogels without structural degradation, as confirmed by Raman and ATR-FTIR spectroscopy. Spectroscopic analysis suggested possible polymer-compound interactions. Release studies demonstrated that diffusion was likely influenced by matrix-compound interactions rather than compound solubility alone. The resulting hydrogels were highly hemocompatible, causing less than 0.1% hemolysis, and displayed composition-dependent functional responses. In the ABTS assay, Z1 showed the strongest radical-scavenging activity at 0.48 mg/mL. Preliminary antimicrobial testing indicated activity against Candida albicans; however, the contribution of DMSO as a solubilizing agent cannot be ruled out. Overall, the developed hydrogels provide a safe matrix primarily with physicochemical functionality and only preliminary biological indications, rather than demonstrated therapeutic efficacy.

Cytochrome P450 (CYP) enzymes are heme-thiolate monooxygenases whose inhibition can result from direct reversible axial ligation of the distal heme iron, perturbation of the axial-water environment, or metabolism-dependent heme interactions. This focused review critically examines the chemical classes used as putative heme-binding groups in small-molecule CYP inhibitors, with emphasis on imidazoles, 1,2,4-triazoles, pyridines, 1,2,3-triazoles, sulfur-containing heterocycles, hydroxamates, nitriles and isonitriles. We discuss the evidential limits of ligand-induced type II spectra, distinguish direct parent–ligand coordination from mechanism-based inactivation, and outline an evidence hierarchy integrating enzymology, UV–Vis spectroscopy, EPR-based methods, structural biology and QM/MM calculations. CYP19A1 is used as a medicinal-chemistry case study illustrating how donor identity, binding geometry, scaffold recognition and selectivity against drug-metabolising and steroidogenic CYP enzymes must be optimized concurrently. We propose practical design and validation principles for the development of selectively heme-directed CYP19A1 inhibitors.

<p><span style="font-size:11pt"><span style="line-height:150%"><span style="font-family:Aptos,sans-serif">W artykule omówiono problem dostępu członków grupy osobowej prokuratorskiej do kursu oficerskiego i zawodowej służby wojskowej w kontekście organizacji Sił Zbrojnych RP oraz standardów NATO. Punktem wyjścia do rozważań była próżnia prawna między normami rekrutacyjnymi resortu obrony a praktyką instytucjonalną prokuratury cywilnej. Nieumocowane w prawie bariery proceduralne i zawężająca interpretacja etatów de facto ograniczają dopływ kadr do pionu wojskowego. W ujęciu prawnodogmatycznym oraz ustrojowo-organizacyjnym wykazano, że kompetencje selekcyjne i opiniodawcze zostały przypisane organom Ministerstwa Obrony Narodowej/wojskowym centrom rekrutacji, rola prokuratury zaś ma charakter organizacyjny (gospodarka etatami), nieselekcyjny. W warstwie funkcjonalnej pokazano znaczenie młodszych kadr (asesorów) dla długofalowej zdolności systemu prokuratury wojskowej do wspierania dyscypliny i odporności Sił Zbrojnych RP. Sformułowano wnioski dotyczące konieczności przywrócenia jednoznacznego rozdziału kompetencji cywilno-wojskowych w procesie naboru, doprecyzowania ścieżek etatowych prokurator/asesor (etaty wojskowe) oraz minimalizacji ryzyka erozji organizacyjnej pionu wojskowego przez praktyki pozanormatywne. W artykule zawarto rekomendacje de lege ferenda oraz organizacyjne, istotne dla planowania kadr, ciągłości obsady oraz interoperacyjności z sojuszniczymi standardami NATO.</span></span></span></p>

Religious beliefs about the causes and meaning of human suffering remain understudied despite their potential relevance to psychological and spiritual functioning. To address this gap, we adapted the Views of Suffering Scale (VOSS) for use with Polish samples. Across three studies, we examined the psychometric properties and clinical correlates of the Polish VOSS. Study 1 (N = 565) tested the internal structure using confirmatory factor analysis (CFA); Study 2 (N = 219) examined convergent and discriminant validity; and Study 3 (N = 346) explored associations with indicators of psychological well-being and distress. Results supported a multidimensional ten-factor structure consistent with the original scale, with acceptable reliability and satisfactory construct validity. Benevolent views of suffering were positively associated with religious commitment, perceived divine engagement, and life satisfaction. In contrast, non-benevolent views were associated with lower religious commitment and higher levels of stress, anxiety, depressive symptoms, and religious/spiritual struggles. Overall, the findings suggest that the Polish VOSS is a valid and reliable instrument for assessing diverse beliefs about suffering and their associations with religious, psychological, and spiritual functioning.

Background/Objectives: The PHASES score is widely used to estimate the 5-year rupture risk of unruptured intracranial aneurysms, yet many patients present with aneurysmal subarachnoid haemorrhage despite low calculated risk. This study aimed to characterise the demographic and aneurysm-related profile of patients with ruptured aneurysms classified as low risk by PHASES. Methods: This retrospective single-centre observational study included 243 consecutive patients with radiologically confirmed ruptured intracranial aneurysms treated between 2013 and 2021. PHASES scores and estimated 5-year rupture risks were calculated retrospectively. Age, sex, arterial hypertension, aneurysm size, location, and multiplicity were analysed using non-parametric statistical methods. Results: The mean PHASES score was 5.16 ± 3.43 points. An estimated 5-year rupture risk below 1% was assigned to 125 patients (51.44%), and 54 patients (22.22%) had PHASES scores of 0–2. Ruptured aneurysms measuring ≤7 mm occurred in 147 patients (60.49%), and 210 patients (86.42%) were younger than 70 years. Internal carotid artery aneurysms were the most frequent overall, whereas anterior communicating artery aneurysms had the smallest median diameter while remaining among the most common rupture sites. Arterial hypertension was associated with larger aneurysm diameter. Conclusions: Low PHASES-estimated risks were common in this cohort of patients presenting with aneurysm rupture. Because the study included no comparison group with unruptured aneurysms, it cannot assess PHASES calibration or predictive performance. PHASES should therefore be used as a population-based decision-support tool rather than a stand-alone predictor of individual rupture risk, with morphology, imaging findings, documented growth, and patient-specific factors incorporated into clinical assessment.

Abstract Adverse childhood experiences, such as violence, abuse, and neglect, are increasingly recognized as significant modifiers of brain development. Here, we tested whether adults with histories of childhood trauma, but without psychiatric comorbidities exhibit altered excitation/inhibition (E/I) balance, as indicated by electroencephalography (EEG) signatures. Participants, divided into low- trauma and high-trauma groups, underwent two experimental conditions: eyes-closed resting-state recording and a reaction-time task with visual stimuli. From these data, we computed 1/f spectral slopes, a widely used electrophysiological marker of E/I balance; we complemented these analyses with a leaky integrate-and-fire (LIF) microcircuit model combined with a biophysically grounded forward-modeling approach to simulate realistic brain signals and derive E/I balance estimates. Group comparisons for both slopes and E/I estimates revealed significant resting-state differences, characterized by a shift toward increased neuronal excitation in the high-trauma group. The high- trauma group exhibited altered stimulus-related 1/f slope dynamics relative to the pre-stimulus baseline, reflecting attenuated neuronal inhibition. E/I ratio measures were not significantly correlated with participants’ transient affective states. Together, these findings suggest that childhood trauma is associated with enduring, trait-like alterations in cortical E/I balance that extend beyond affective state and manifest across both resting and task-related brain dynamics. Significance Statement Childhood trauma is a major risk factor for mental illness, yet its lasting effects on basic brain physiology remain poorly understood. Using electroencephalography combined with biophysically grounded neural circuit modeling, we show that young adults with a history of childhood interpersonal trauma exhibit a persistent shift toward cortical hyperexcitation at rest and a reduced ability to engage inhibitory control during cognitive processing. These effects occur even in individuals without psychiatric diagnoses and are independent of current anxiety or depression, indicating a trait-like neurophysiological footprint of early adversity. This excitation-inhibition imbalance may represent a transdiagnostic vulnerability linking childhood trauma to later psychopathology.

L-carnitine plays an important role in fatty acid metabolism associated with peroxisomal β-oxidation in Yarrowia lipolytica during growth on lipid-rich substrates. This study investigated substrate-dependent L-carnitine handling in two Y. lipolytica strains, A-101 and ATCC 9793, cultivated in lipid-rich industrial biofuel waste (SK medium) and carbohydrate-based YPG medium under various conditions. In YPG medium, free L-carnitine reached up to 22.85 mg/100 g wet biomass in ATCC 9793 and 7.09 mg/100 g wet biomass in A-101. In YPG-grown Y. lipolytica A-101, supplementation with trimethyllysine (TML), iron, and L-ascorbic acid, selected based on their proposed roles in L-carnitine biosynthesis, increased the free L-carnitine concentration by up to 2.5-fold relative to the unsupplemented control. In contrast, the biomass of both strains grown in SK medium contained less than 1 mg of L-carnitine per 100 g of wet biomass, indicating marked substrate-dependent differences in L-carnitine handling under lipid-rich (SK) growth conditions. The addition of TML, iron, and L-ascorbic acid to SK medium resulted in approximately 1.2–1.3-fold higher OD₅₅₀ values after 10 h of cultivation. To further characterize substrate-dependent L-carnitine handling, untargeted metabolomic profiling of post-culture supernatants of the A-101 strain and comparative in silico analyses, including sequence- and structure-based homology assessment, were performed. Despite the presence of putative homologues of L-carnitine biosynthesis-related proteins, the combined metabolomic and comparative in silico evidence supported substrate-dependent L-carnitine handling rather than predominant de novo biosynthesis under the tested conditions. These findings improve our understanding of the metabolic adaptation of Y. lipolytica to lipid-rich industrial substrates and highlight the importance of cultivation environment in determining L-carnitine availability and accumulation.