BACKGROUND Midazolam, a commonly used sedative, faces challenges in cancer therapy due to its central nervous system (CNS) toxicity and suboptimal targeting of tumor sites. This study explores the use of poly (lactic-co-glycolic acid) (PLGA) nanoparticles to enhance the delivery of Midazolam, aiming to improve antitumor efficacy while minimizing CNS toxicity. MATERIAL AND METHODS We developed Midazolam-loaded PLGA nanoparticles (Midazolam PLGA NPs) using the ultrasonic emulsification-solvent evaporation technique. These nanoparticles were thoroughly characterized for particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, drug loading, and stability. We assessed cellular uptake and cytotoxicity via the MTT assay, while organ accumulation was quantified using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The safety profile was evaluated by monitoring body weight changes in A549 tumor-bearing mice. RESULTS The Midazolam PLGA nanoparticles exhibited a spherical shape, uniform size, high encapsulation efficiency, and excellent colloidal stability. In vitro release studies indicated that 62.51% of Midazolam was released within 24 hours. Enhanced cellular uptake was noted for the nanoparticles in comparison to the solution, with significant accumulation at tumor sites and increased free drug release. The nanoparticles effectively killed tumor cells while sparing normal tissues, demonstrating superior antitumor activity compared to the Midazolam solution. Importantly, treated mice maintained stable body weight, suggesting a favorable safety profile. CONCLUSIONS Midazolam-loaded PLGA nanoparticles present a promising approach for targeted cancer therapy. They enhance encapsulation, stability, and selective tumor cell cytotoxicity, resulting in greater antitumor efficacy with minimal adverse effects compared to conventional Midazolam solutions.

BACKGROUND The development and progression of prostate cancer are multistep processes involving several growth factors, hormones, and cytokines. This study aimed to measure the serum concentrations of different cytokines and determine their correlation with prostate-specific antigen (PSA) levels and disease grade in patients with prostate adenocarcinoma. MATERIAL AND METHODS This cross-sectional study was conducted from March 2023 to March 2024 at the Clinic of Oncology of the University Hospital Center in Mostar, Bosnia and Herzegovina. Altogether, 50 male patients with prostate adenocarcinoma were included, of whom 28 had no proven metastases (PC group) and 22 had metastatic disease (MPC group). Serum concentrations of total (tPSA), free (fPSA), and complexed (cPSA) PSA were determined using a chemiluminescent microparticle immunoassay, whereas serum concentrations of cytokines were measured using a flow cytometry bead-based assay. RESULTS The MPC group had higher serum tPSA, fPSA, and cPSA levels than the PC group. The PC group had significantly higher serum levels of monocyte chemotactic protein (MCP)-1 than the MPC group (P=0.008). In the PC group, serum levels of interleukin (IL)-10 significantly correlated with cPSA. In the MPC group, serum concentrations of IL-1ß, tumor necrosis factor (TNF)-alpha, and IL-23 significantly correlated with disease grade. CONCLUSIONS Our study emphasizes the importance of MCP-1 in the development of prostate cancer, while IL-10 was the only cytokine whose serum level significantly correlated with cPSA. Serum concentrations of IL-1ß, TNF-alpha, and IL-23 may serve as potential biomarkers for disease grade.

BACKGROUND Modern prosthetic technologies make it possible to fabricate prosthetic restorations without material loss and to make prosthetic restorations with complex geometric shapes in a relatively simple way. One such technology is selective laser melting (SLM), or additive manufacturing of metal materials, better known as 3D printing from metal or selective laser melting, but currently the most commonly used method is casting. The present study investigated use of dental chromium-cobalt alloys for prosthetic bridges and compared methods of processing dental chromium-cobalt alloys to obtain the best mechanical properties. MATERIAL AND METHODS We used dental chromium-cobalt alloy (SCHEFTNER GMBH) for laser melting StarbondCoSEeasy Powder with grain size of 10-30 µm and StarbondCoS alloy casting, made in accordance with the European standard EN ISO 22674. SLM-made specimens and induction melted alloy castings were prepared for the study. A centrifugal casting system with induction current melting of the metal alloy was used to produce the samples. The melting and casting process is automatic and limits changes in chemical composition. RESULTS The results show that none of the samples changed their chemical composition, while the samples made by SLM had better mechanical properties. CONCLUSIONS The SLM technique makes it possible to produce restorations faster and cheaper without any loss of quality compared to restorations made with the casting technique. Casting technology reduces mechanical properties, but still provides good mechanical properties.

BackgroundThe COVID-19 pandemic has brought changes and challenges to nursing students. However, little is known about the prevalence of academic burnout among nursing students in this challenging circumstance. This study aimed to assess nursing student academic burnout and its influencing factors.Material/MethodsWe conducted a sample survey of a 4-year undergraduate nursing university in Wuhu, Anhui Province, China. The social-demographic information questionnaire, Academic Burnout Scale, Connor-Davidson Resilience Scale, Impact of Event Scale-6, Patient Health Questionnaire-2, and Professional Identity Scale were used. Stepwise multiple linear regression was used to clarify the relationship among sociodemographic characteristics, resilience, and academic burnout.ResultsOf all the study participants, 51.30% had a certain degree of academic burnout. Academic year, satisfaction with specialty, satisfaction with online learning, professional identity, and psychological resilience were negatively correlated with academic burnout among nursing students. Depression was positively correlated with academic burnout.ConclusionsNursing students had a high degree of academic burnout. Academic year, satisfaction with specialty, satisfaction with online learning, professional identity, and psychological resilience were protective factors that reduced nursing students’ academic burnout.

BackgroundPatients who undergo open-heart surgery often experience widespread musculoskeletal and pulmonary complications. These can interfere with their functioning, resulting in soft tissue changes, worsening postural changes, and poor respiratory performance. Therefore, the prospective study aimed to compare forward head angle (FHA) and forward shoulder angle (FSA), maximal inspiratory pressure (MIP), and self-reported breathing dysfunction before and after open-heart surgery.Material/MethodsIn a prospective observational study of 106 patients, men and women scheduled for open-heart surgery were enrolled. Prior to surgery and before discharge from the hospital, all patients were required to assess FHA and FSA using 2-dimensional motion analysis software, MIP using a respiratory pressure meter, and breathing dysfunction using the 25-item Self Evaluation of Breathing Questionnaire (SEBQ). Paired t test was used to compare differences between before and after surgery. To evaluate associations, logistic regression analysis was performed.ResultsOf the 106 patients recruited, 73 completed the study. FHA (−Δ6.55±4.77, P<0.001), FSA (−Δ4.82±7.29, P<0.001), and MIP (−Δ14.07±17.02 cmH2O, P<0.001) values were decreased prior to discharge from the hospital compared with values before surgery. Regression analysis found that decreased MIP after median sternotomy was associated with an increase in FHA and breathing dysfunction in patients after open-heart surgery.ConclusionsAfter open-heart surgery, increased FHA and breathing dysfunction (SEBQ) were associated with reduced MIP, which may be associated with poor respiratory performance after surgery. Therefore, postoperative physiotherapy in this patient group should aim to improve postural changes.

BackgroundRicin protein derived from Ricinus communis seeds is known to have a high toxicity to humans and animals. Several studies revealed that ricin, belonging to ribosome inactivating protein-I, has cytotoxic properties against various types of cancer cell lines.Material/MethodsCrude ricin (CR) from the seeds of R. communis was investigated for its cytotoxicity on the A549 cancer cell lines using the MTS assay, and the cell death mechanism was explored using flow cytometry and Western blot methods. The cell migration was measured using a scratch/wound-healing method and the autophagy activity was explored using Western blotting.ResultsCR showed cytotoxicity against A549 cancer cell lines, with an IC50 of 40.94 ppm. CR induced apoptosis and necrosis, but apoptosis occurred more frequently than necrosis. Apoptosis induced by CR was mediated by the activation of caspase-9 and caspase-3. CR inhibited cell migration in a concentration- and time-dependent manner, with the highest effect occurred at the concentration of 1.0 ppm. The autophagic experiment showed that CR inhibited autophagy in A549 lung cancer cells by decreasing Beclin-1 levels while increasing Atg5 levels in a concentration-dependent manner and CR decreased LC3-II level while increasing p62 level. Cisplatin treatment also inhibited autophagy as it exhibited the same effect on those autophagic proteins as CR.ConclusionsOur findings suggest that CR might be a potential candidate for anticancer drugs, but further study is needed to verify its anticancer properties.

BACKGROUND For patients with hereditary coagulopathies such as hemophilia, the most common dental problem is spontaneous oral bleeding caused by daily oral hygiene habits like tooth brushing. Because of fear of bleeding, children with hemophilia often skip routine oral hygiene procedures, which can lead to dental caries and periodontal diseases. This case control study aimed to evaluate the oral hygiene awareness and hygiene practices of children with hemophilia from 6 to 18 years of age in Bulgaria. MATERIAL AND METHODS This study was conducted over 4 years and included 31 patients (children). A sociological approach was used, with direct individual questionnaires for self-assessment of dental habits. Statistical analyses were performed using SPSS. RESULTS There was no significant difference between groups in methods of oral hygiene. The duration of oral hygiene procedures was 1 min (n=5, 16.13±6.61%) or 2 min (n=13, 41.94±8.86%), which was considered insufficient for proper oral hygiene. Children who had received oral hygiene advice by a dentist brushed their teeth significantly longer (n=9, 69.23±12.80%) than those who had not. There was a considerable difference between the reasons for the last dental visit between the groups of children (χ²=5.18, P<0.05). CONCLUSIONS Children with hemophilia have high awareness of oral hygiene methods; however, more attention should be focused on additional individual educational methods at the dental office. Frequent professional and self-assessment of the oral hygiene routine of children with hemophilia could identify the factors compromising dental status in this vulnerable population.

BackgroundInflammation is the body’s first response to an illness that causes irritation or infection. Inflammation is tightly correlated with aging, which is a progressive degenerative process. Conditioned medium (CM) from adipose tissue-derived mesenchymal stem cells (CM-ATMSCs) has been shown to stimulate collagen synthesis and dermal fibroblast migration, as well as reduce wrinkles and improve wound healing. This study aimed to observe the production of inflammatory modulators – interleukin (IL)-1α, IL-6, IL-10, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) – in CM-ATMSCs treated with fresh frozen plasma (FFP) at passages 3 (P3), 7, 11, and 15.Material/MethodsATMSCs P3 were obtained from liposuction of female donors, and the CM from ATMSCs was collected. Measurement of these cytokines was performed with ELISA.ResultsAt many passages, IL-6, a proinflammatory modulator, was discovered to be the most powerful modulator among FFP- and non-FFP-treated cells. However, CM-ATMSCs treated with FFP and in the late passage have significant differences (P<0.05) compared to non-FFP treatments and in other passages in their effects on secretion of inflammatory modulators.ConclusionsIn conclusion, CM-ATMSC has the potential to secrete proinflammatory modulators.

BackgroundStudies have shown that lung inflammation affects lung function, with life-threatening results. Vitamin D may play an important role in inhibiting inflammatory cytokines. Vitamin D deficiency is related to several lung problems, including respiratory distress syndrome, alveolar inflammation, epithelial damage, and hypoxia. Few studies have evaluated the benefits of vitamin D in preventing inflammation in alveolar cells.Material/MethodsWe developed a cell inflammation model induced by lipopolysaccharide (LPS) treatment. The effects of vitamin D on LPS-induced inflammation in A549 cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the anti-inflammatory mechanism of vitamin D was evaluated using western blot analysis.ResultsOur results indicated that vitamin D promoted A549 cell survival following LPS-induced inflammation by downregulating nuclear factor nuclear factor kappa light chain enhancer of activated B cells, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-12.ConclusionsOur results indicated that vitamin D has the potential to manage lung inflammation, although further studies are needed.

BackgroundSuccessful endodontic therapy requires a fluid-tight apical seal. The aim of this in vitro study was to evaluate and compare the apical sealing ability of 3 root canal sealers: Apexit Plus, AH Plus, and Resilon/Epiphany sealers.Material/MethodsSamples of 152 single-rooted teeth were divided into 2 test groups, and each group was divided into 3 subgroups based on the preparation and obturation technique. After preparation with the step-back technique, the first group of root canals were obturated with lateral gutta-percha compaction in combination with AH Plus sealer or Apexit Plus or with the Resilon/Epiphany system alone. In the second group, preparation was done with the crown-down technique and root canals were then obturated with Thermafil obturator in combination with AH Plus or Apexit Plus or with Resilon/Epiphany sealer alone. Apical leakage was determined using a dye leakage test observed with a stereomicroscope. The degree of dye leakage was assessed using the t test to comparing the arithmetic averages of the groups.ResultsIn the groups prepared with the step-back technique, the average dye leakage was lower in samples obturated with Resilon/Epiphany, than in those filled with AH Plus/lateral gutta-percha compaction or Apexit Plus/lateral gutta-percha compaction. In groups prepared with the crown-down technique and obturated with the Resilon/Epiphany system, the average dye leakage was lower than in those filled with AH Plus/Thermafil obturation and those filled with Apexit Plus/Thermafil obturation.ConclusionsAlthough all preparation and obturation techniques showed dye penetration, the crown-down technique paired with the Resilon/Epiphany system showed the least leakage.