Poznan University of Medical Sciences

Familial hypocalciuric hypercalcemia (FHH) is a rare genetic disorder of calcium regulation. FHH type 3 (FHH3), caused by pathogenic variants in AP2S1, may present with clinically significant complications. Data on the treatment of this rare disorder is limited. CASE DESCRIPTION: We report an 11-year-old girl with a de novo heterozygous pathogenic variant in AP2S1 (NM_004069.6): c.44G>T p.(Arg15Leu). At the age of seven, our patient presented with hypercalcemia, hypocalciuria, and elevated parathyroid hormone (PTH), which were accompanied by low bone mineral density and persistent neurodevelopmental difficulties. Primary hyperparathyroidism and causative variants in the CASR gene were excluded, and cinacalcet was initiated. After a dose titration and vitamin D3 dose adjustments, a normalization of serum calcium and PTH was achieved, and symptoms improved substantially, although lumbar bone mineral density declined further, and neurological symptoms remained. CONCLUSIONS: This case demonstrates cinacalcet as an effective and well-tolerated therapy in FHH3, with unresolved questions regarding skeletal and neurocognitive outcomes.

Background: Interpersonal violence is one of the most common causes of maxillofacial injuries. These injuries can range from minor soft-tissue injuries to serious, life-threatening conditions. This is particularly important when injuries occur in an exposed and vulnerable area of the body, such as the facial area. This study aimed to analyse the types of maxillofacial injuries, assess a profile of a typical victim of violence and determine the circumstances of the injury. Methods: A retrospective review was performed on the clinical data of patients managed for maxillofacial trauma resulting from interpersonal violence at the Department of Maxillofacial Surgery, University Clinical Hospital, Poznan, spanning the period from 2021 to 2025. Results: The study group included 510 patients, of which 95.41% were males, and the median age in the study group was 34 years. Furthermore, 14.71% of patients were under the influence of alcohol at the time of the violent incident. Most injuries occurred in 2022 (25.88%). Regarding months, June had the highest reported incidents (10.59%), while Saturday was the most injury-prone day (25.10%). The median days of hospitalisation in the study group was five. The mandible was the most frequently affected area. The most common types of fractures were single mandible fractures (30.59%) and double mandible fractures (27.25%). Most injuries were treated surgically (96.67%). In 10.20% of cases, the intervention of other specialists was needed. Conclusions: It is important to effectively prepare medical staff to receive patients with a history of interpersonal violence to diagnose and treat these types of injuries properly.

Background/Objectives: Psilocybin has re-emerged as a promising intervention for neuropsychiatric disorders including major depressive disorder, treatment-resistant depression, anxiety associated with life-threatening illness, obsessive compulsive disorder, and substance use disorders. However, conventional randomized controlled trials (RCTs)-the current gold standard in evidence-based medicine-may not adequately capture the therapeutic complexity of psilocybin, which depends not only on pharmacological action but also on contextual, psychological, and interpersonal factors. This critical narrative review aimed to evaluate the adequacy of existing clinical research frameworks for assessing psilocybin's therapeutic potential and to explore alternative methodologies that may better reflect real-world clinical conditions. Methods: Using the Web of Science Core Collection database, we identified and analysed the ten most cited clinical studies on psilocybin published between 2015 and 2025 inclusive. Additional literature was included through reference cross-checking, systematic reviews, meta-analyses, and interdisciplinary sources covering neurobiology, history, and real-world evidence (RWE). The review synthesizes clinical outcomes, methodological constraints, and epistemic considerations relevant to psychedelic-assisted therapy. Results: Evidence from highly cited trials demonstrates rapid and sustained antidepressant and anxiolytic effects of psilocybin, with notable benefits also observed in addiction treatment. However, significant methodological limitations were identified, including selection bias, challenges in placebo design and blinding, small sample sizes, and the underrepresentation of diverse populations. Psilocybin outcomes were strongly influenced by subjective experience and contextual factors such as set and setting. Emerging RWE studies revealed heterogeneous patterns of response and provided insights unattainable through RCTs alone. Conclusions: Psilocybin shows considerable therapeutic promise, but current RCT methodologies capture only part of its clinical effects. Comprehensive evaluation will require larger and more diverse clinical trials, long-term follow-up, standardized psychotherapeutic protocols, and the integration of RWE to reflect real-world practice. Psychedelic-assisted therapy should be conceptualized as a complex intervention that combines pharmacological and psychotherapeutic components.

Nursing students face high academic and emotional demands that may adversely affect their mental well-being and psychological resources. Understanding the relationships between stress, life orientation, and sense of coherence is essential for developing effective support strategies. This study aimed to examine the mediating role of perceived stress in the relationship between life orientation and sense of coherence among nursing students, with the year of study as a moderator. A multicentre cross-sectional study was conducted between October and December 2023 among 2,689 undergraduate nursing students in Poland aged 18–30 years. Data were collected using a sociodemographic questionnaire and standardized instruments: LOT-R, SOC-29, and PSS-10. Moderated mediation analyses were performed. Most participants reported high levels of perceived stress and high dispositional optimism, while sense of coherence scores were moderate. Optimism showed a negative direct association with meaningfulness, which strengthened in the second year of study and became partially mediated by stress in the third year. In the first two years, higher optimism was associated with lower manageability; this relationship weakened in the third year, suggesting adaptive changes. The third year emerged as a critical period, during which stress significantly reduced comprehensibility and meaningfulness and played a stronger mediating role between optimism and sense of coherence. Perceived stress mediates the relationship between life orientation and sense of coherence in nursing students, with patterns differing across years of study. These findings highlight the need for targeted educational and psychological interventions to enhance stress management, emotional resilience, and psychological resources, particularly in later stages of nursing education. Not applicable.

Background: Malnutrition and its risk are prevalent in older adults and contribute to frailty, morbidity, and mortality. Poor oral health-particularly tooth loss and inadequate prosthetic rehabilitation-may impair chewing, limit dietary variety, and accelerate nutritional decline. We investigated associations between dentition status, denture use, and nutritional status in a nationally representative sample of Polish older adults. Methods: We analyzed data from 5214 participants aged ≥60 years from the nationwide cross-sectional PolSenior2 study. Dentition status was classified as functional dentition (≥20 teeth), partial dentition (1-19 teeth), or edentulism (0 teeth). Nutritional status was assessed using the Mini Nutritional Assessment-Short Form (MNA-SF); impaired nutritional status was defined as MNA-SF <12 (malnourished or at risk). Additional indicators included hypoalbuminemia (<35 g/L) and small calf circumference (<31 cm). Associations were tested using chi-square and multivariable logistic regression adjusted for age, sex, education, and place of residence. Results: Functional dentition was present in 15.5%, partial dentition in 48.1%, and edentulism in 36.4% of participants. The proportion of edentulous individuals increased across worsening MNA-SF categories (26.2% in well-nourished, 41.8% in at risk, 46.9% in malnourished). In adjusted models, edentulism was associated with higher odds of impaired nutritional status compared with functional dentition (OR: 1.66; 95% CI: 1.32-2.10; p < 0.001), while partial dentition showed a non-significant trend (OR: 1.22; 95% CI: 0.98-1.52; p = 0.077). Among edentulous participants, denture use was more common in well-nourished individuals than in those with impaired nutritional status (93.0% vs. 77.2%), suggesting a possible association between active prosthetic rehabilitation and better nutritional status. Conclusions: In Polish older adults, tooth loss-particularly edentulism-is associated with poorer nutritional status. Screening for malnutrition risk may benefit from incorporating basic oral health and denture-use assessment while improved access to prosthetic rehabilitation may support nutritional resilience in ageing populations.

Background/Objectives: Management of bipolar disorder is marked by variability in lithium response, with responders constituting a distinct clinical subgroup. Although pharmacogenetic studies implicate polymorphisms in neuroplasticity-related genes (BDNF) and hypothalamic-pituitary-adrenal (HPA) axis regulators (NR3C1), the underlying biophysical mechanisms remain poorly characterized. This study aims to bridge this structural-mechanistic gap by quantifying the atomic-level effects of key lithium-response polymorphisms on protein-protein interaction stability and conformational dynamics. Methods: Variant sequences for BDNF rs6265 and NR3C1 rs56149945 were generated and structurally modeled with SWISS-MODEL. Protein-protein interaction analyses focused on the BDNF-TrkB and NR3C1-FKBP5 systems. Structural alignment and conformational comparisons were performed with ChimeraX and US-align, while interaction energetics were evaluated with PRODIGY and HawkDock. Conformational flexibility was assessed using CABS-flex through RMSF analysis. Results: Structural validation showed acceptable model quality. Binding analyses indicated stronger interactions in the variant complexes. In the BDNF-TrkB complex, binding affinity shifted from -13.8 to -15.1 kcal/mol with an ~8.5-fold lower dissociation constant, while the NR3C1-FKBP5 variant complex shifted from -16.3 to -18.8 kcal/mol with an ~65-fold lower dissociation constant. MM/GBSA calculations supported increased stability, with binding energies changing from -61.98 to -83.91 kcal/mol (BDNF-TrkB) and from -18.88 to -31.25 kcal/mol (NR3C1-FKBP5). Structural superposition showed high conservation of global folds (pruned RMSD 0.779 Å and 0.310 Å; TM-scores 0.753 and 0.967). RMSF profiles were largely overlapping, indicating localized interface adjustments rather than global conformational changes. Conclusions: These findings suggest that lithium-response polymorphisms may modulate protein-protein interaction stability while preserving overall structure, providing a structural framework for exploring genetic influences on lithium treatment response.

Endoplasmatic reticulum (ER) stress is an imbalance between the load of unfolded proteins and the ability of cellular mechanisms to handle it. Under the influence of this stress, cells activate the unfolded protein response (UPR). The molecular mechanisms of ER stress have been repeatedly linked to metabolic and inflammatory diseases, such as obesity and allergic inflammation. The aim of our study was to investigate if the allergic inflammation in adipocytes affects the expression of UPR pathway genes and Ormdl3 and whether miRNA-665 can modify inflammatory response in adipocytes. We isolated rat preadipocytes and treated them with IL-13 to induce allergic inflammation. Later, we transfected them with miRNA-665 inhibitor. RNA was isolated from adipocytes and analyzed by qPCR. From cell culture medium, we performed an LDH assay and ELISA for secreted IL-6 and TNFα proteins. A comparison between control cells and IL-13-treated cells showed significant differences in the expression of most of the studied UPR pathway genes, Ormdl3 and Bax. Comparing the IL-13-treated cells after miR-665 transfection with non-transfected ones, we observe significant differences only in Ire1α gene. Our research suggests that allergic inflammation induces an adaptive UPR in adipocytes and miR-665 may selectively modify this response, triggering the IRE1/XBP1 axis.

The objective of the present study is to examine the association between the presence of various forms of matrix metalloproteinase genes (MMP-1, MMP-9, TIMP-1 and TIMP-2) and their tissue inhibitors, and the incidence of intraventricular haemorrhage (IVH) in premature neonates. The data for this study were obtained from samples of peripheral venous blood, which were collected and stored post-delivery. The techniques employed for the purpose of genotyping were polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The population that was examined comprised 100 patients with a gestational age (GA) ranging from 22 to 33 weeks and birth weight (BW) ranging from 432 to 2100 g. In the cohort of enrolled patients, 48 cases of IVH were observed. As indicated by the findings of this study, the majority of observed correlations between MMP-1, MMP-9, TIMP-1, and TIMP-2 variants and IVH did not demonstrate statistical significance, with the exception of the T allele of TIMP1 rs4898. Nevertheless, the findings of this study indicated a potential impact of these variants on the incidence of IVH. The present study suggests that further research is required to elucidate the role of MMP/TIMP polymorphisms in the aforementioned disease.