BACKGROUND AND PURPOSE: CNS embryonal tumor with pleomorphic adenoma gene-like 1 (PLAGL1)/pleomorphic adenoma gene-like 2 (PLAGL2) amplification (ET, PLAGL) is a newly identified, highly malignant pediatric tumor. Systematic MRI descriptions of ET, PLAGL are currently lacking. MATERIALS AND METHODS: MRI data from 19 treatment-naïve patients with confirmed ET, PLAGL were analyzed. Evaluation focused on anatomic involvement, tumor localization, MRI signal characteristics, DWI behavior, and the presence of necrosis and hemorrhage. Descriptive statistics (median, interquartile range, percentage) were assessed. RESULTS: Ten patients had PLAGL1 and nine had PLAGL2 amplifications. The solid components of the tumors were often multinodular with heterogeneous enhancement (mild to intermediate in 47% and intermediate to strong in 47% of cases). Nonsolid components included cysts in 47% and necrosis in 84% of the cases. The tumors showed heterogeneous T2WI hyper- and isointensity (74%), relatively little diffusion restriction (ADC values less than contralateral normal-appearing WM in 36% of cases with available DWI), and tendencies toward hemorrhage/calcification (42%). No reliable distinction was found between PLAGL1- and PLAGL2-amplified tumors or compared with other embryonal CNS tumors. CONCLUSIONS: The study contributes to understanding the imaging characteristics of ET, PLAGL. It underscores the need for collaboration in studying rare pediatric tumors and advocates the use of harmonized imaging protocols for better characterization.

• MeSH
• amplifikace genu MeSH
• dítě MeSH
• DNA vazebné proteiny genetika   MeSH
• germinální a embryonální nádory diagnostické zobrazování   patologie   MeSH
• kojenec MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mladiství MeSH
• nádorové supresorové proteiny MeSH
• nádory centrálního nervového systému diagnostické zobrazování   patologie   MeSH
• nádory mozku diagnostické zobrazování   patologie   MeSH
• předškolní dítě MeSH
• proteiny buněčného cyklu MeSH
• proteiny vázající RNA MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma affecting children and young adults. About 30% of patients develop therapy resistance therefore new precision medicine drugs are highly warranted. Multiple rounds of structure-activity optimization of Caffeic Acid Phenethyl Ester have resulted in CM14. CM14 causes upregulation of genes involved in oxidative stress response and downregulation of DNA replication genes leading to G2/M arrest and subsequent apoptosis induction. In accordance with this, an unbiased proteomics approach, confocal microscopy and molecular modeling showed that TUBGCP2, member of the centrosomal γ-TuRC complex, is a direct interaction partner of CM14. CM14 overcomes ALK inhibitor resistance in ALCL and is also active in T-cell Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia. Interestingly, CM14 also induced cell death in docetaxel-resistant prostate cancer cells thus suggesting an unexpected role in solid cancers. Thus, we synthesized and thoroughly characterized a novel TUBGCP2 targeting drug that is active in ALCL but has also potential for other malignancies.

• MeSH
• apoptóza * účinky léků   MeSH
• centrozom * účinky léků   metabolismus   MeSH
• fenethylalkohol * analogy a deriváty   farmakologie   chemie   MeSH
• kyseliny kávové * farmakologie   chemie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky * farmakologie   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Skin represents the largest organ in the human body, functioning as a protective barrier against environmental factors while playing a critical role in thermoregulation. Acne vulgaris is recognized as the most common dermatological condition affecting adolescents, and if left untreated, it can result in lasting skin damage and associated psychosocial challenges. This study aims to develop innovative polymeric biomaterials that could effectively support the treatment of acne vulgaris. The synthesis of these biomaterials involves the use of polyethylene glycol 6000, sodium alginate, and the antioxidant protein glutathione (GHS) to create polymeric hydrogels. These hydrogels were generated via a UV-mediated crosslinking process. To enhance the functional properties of the hydrogels, zinc oxide microparticles (ZnO), synthesized through a wet precipitation method, were incorporated into the formulations. Characterization of the ZnO was performed using Fourier-Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), particle sizer analysis, and Scanning Electron Microscopy (SEM). Additionally, the bioactivity of the synthesized materials was evaluated through incubation in media simulating physiological body fluids. The cytotoxic effects of the biomaterials were assessed using an indirect test on mouse fibroblast (L929) cells, in accordance with ISO 10993-5 guidelines. The results of our research indicate that the developed biomaterials exhibit potential as a carrier for active substances, contributing positively to the treatment of acne vulgaris and potentially improving overall skin health.

• MeSH
• acne vulgaris farmakoterapie   MeSH
• algináty chemie   MeSH
• biokompatibilní materiály chemie   farmakologie   MeSH
• buněčné linie MeSH
• fibroblasty účinky léků   metabolismus   MeSH
• glutathion * metabolismus   MeSH
• hydrogely * chemie   MeSH
• kůže * účinky léků   metabolismus   MeSH
• lidé MeSH
• myši MeSH
• nosiče léků chemie   MeSH
• oxid zinečnatý * chemie   farmakologie   MeSH
• regenerace účinky léků   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Nowadays, most of the newly developed active pharmaceutical ingredients (APIs) consist of cohesive particles with a mean particle size of <100μm, a wide particle size distribution (PSD) and a tendency to agglomerate, therefore they are difficult to handle in continuous manufacturing (CM) lines. The current paper focuses on the impact of various glidants on the bulk properties of difficult-to-handle APIs. Three challenging powders were included: two extremely cohesive APIs (acetaminophen micronized (APAPμ) and metoprolol tartrate (MPT)) which previously have shown processing issues during different stages of the continuous direct compression (CDC)-line and a spray dried placebo (SD) powder containing hydroxypropylmethyl cellulose (HPMC), known for its sub-optimal flow with a high specific surface area (SSA) and low density. Four flow-enhancing excipients were used: a hydrophilic (Aerosil® 200) and hydrophobic (Aerosil® R972) fumed silica grade, a mesoporous silica grade (Syloid® 244FP), and a calcium phosphate excipient (TRI-CAFOS® 200-7). The APIs and binary API/glidant blends (varied between 0.5-2.75 w/w%) were characterized for their bulk properties relevant for CDC. The results indicated that optimizing different bulk parameters (e.g., density, flow, compressibility..) of an API required varying weight percentages of the glidant (e.g., different surface area coverage (SAC)) depending on the APIs. Moreover, even at similar SAC, the impact of the glidant on the bulk characteristic of the APIs depended on the glidant type properties. While nano-sized silicon dioxide were effective for improving the flowability of a powder, other glidants (mesoporous silica and tricalcium phosphate (TCP)) showed also promise as alternatives. Additionally, an excess of glidant, referred to as oversilication, negatively impacted some bulk parameters, but other characteristics were unaffected. Finally, to determine the appropriate concentration of the different classes of glidants, SAC calculations, an understanding of the glidant's working mechanism, and knowledge about the API's characteristics (i.e., morphology, compressibility, flowability, aeration, density, and wall friction) are required. This study confirmed the necessity of including various material characterization techniques to assess the impact of glidants on the bulk characteristics of APIs.

• MeSH
• deriváty hypromelózy * chemie   MeSH
• farmaceutická chemie metody   MeSH
• fosforečnany vápenaté * chemie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• metoprolol * chemie   MeSH
• nerozplněné léky MeSH
• oxid křemičitý chemie   MeSH
• paracetamol * chemie   MeSH
• pomocné látky * chemie   MeSH
• prášky, zásypy, pudry * MeSH
• příprava léků metody   MeSH
• reologie * MeSH
• velikost částic * MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND PURPOSE: Diffuse gliomas, a heterogeneous group of primary brain tumors, have traditionally been stratified by histology, but recent insights into their molecular features, especially the IDH mutation status, have fundamentally changed their classification and prognosis. Current diagnostic methods, still predominantly relying on invasive biopsy, necessitate the exploration of noninvasive imaging alternatives for glioma characterization. MATERIALS AND METHODS: In this prospective study, we investigated the utility of the spherical mean technique (SMT) in predicting the IDH status and histologic grade of adult-type diffuse gliomas. Patients with histologically confirmed adult-type diffuse glioma underwent a multiparametric MRI examination using a 3T system, which included a multishell diffusion sequence. Advanced diffusion parameters were obtained using SMT, diffusional kurtosis imaging, and ADC modeling. The diagnostic performance of studied parameters was evaluated by plotting receiver operating characteristic curves with associated area under curve, specificity, and sensitivity values. RESULTS: A total of 80 patients with a mean age of 48 (SD, 16) years were included in the study. SMT metrics, particularly microscopic fractional anisotropy (μFA), intraneurite voxel fraction, and μFA to the third power (μFA3), demonstrated strong diagnostic performance (all AUC = 0.905, 95% CI, 0.835-0.976; P < .001) in determining IDH status and compared favorably with diffusional kurtosis imaging and ADC models. These parameters also showed a strong predictive capability for tumor grade, with intraneurite voxel fraction and μFA achieving the highest diagnostic accuracy (AUC = 0.937, 95% CI, 0.880-0.993; P < .001). Control analyses on normal-appearing brain tissue confirmed the specificity of these metrics for tumor tissue. CONCLUSIONS: Our study highlights the potential of SMT for noninvasive characterization of adult-type diffuse gliomas, with a potential to predict IDH status and tumor grade more accurately than traditional ADC metrics. SMT offers a promising addition to the current diagnostic toolkit, enabling more precise preoperative assessments and contributing to personalized treatment planning.

• MeSH
• difuzní magnetická rezonance metody   MeSH
• dospělí MeSH
• gliom * diagnostické zobrazování   patologie   MeSH
• isocitrátdehydrogenasa * genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mutace MeSH
• nádory mozku * diagnostické zobrazování   patologie   MeSH
• prospektivní studie MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• stupeň nádoru MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a common adult leukemia characterized by the accumulation of neoplastic mature B cells in blood, bone marrow, lymph nodes, and spleen. The disease biology remains unresolved in many aspects, including the processes underlying the disease progression and relapses. However, studying CLL in vitro poses a considerable challenge due to its complexity and dependency on the microenvironment. Several approaches are utilized to overcome this issue, such as co-culture of CLL cells with other cell types, supplementing culture media with growth factors, or setting up a three-dimensional (3D) culture. Previous studies have shown that 3D cultures, compared to conventional ones, can lead to enhanced cell survival and altered gene expression. 3D cultures can also give valuable information while testing treatment response in vitro since they mimic the cell spatial organization more accurately than conventional culture. METHODS: In our study, we investigated the behavior of CLL cells in two types of material: (i) solid porous collagen scaffolds and (ii) gel composed of carboxymethyl cellulose and polyethylene glycol (CMC-PEG). We studied CLL cells' distribution, morphology, and viability in these materials by a transmitted-light and confocal microscopy. We also measured the metabolic activity of cultured cells. Additionally, the expression levels of MYC, VCAM1, MCL1, CXCR4, and CCL4 genes in CLL cells were studied by qPCR to observe whether our novel culture approaches lead to increased adhesion, lower apoptotic rates, or activation of cell signaling in relation to the enhanced contact with co-cultured cells. RESULTS: Both materials were biocompatible, translucent, and permeable, as assessed by metabolic assays, cell staining, and microscopy. While collagen scaffolds featured easy manipulation, washability, transferability, and biodegradability, CMC-PEG was advantageous for its easy preparation process and low variability in the number of accommodated cells. Both materials promoted cell-to-cell and cell-to-matrix interactions due to the scaffold structure and generation of cell aggregates. The metabolic activity of CLL cells cultured in CMC-PEG gel was similar to or higher than in conventional culture. Compared to the conventional culture, there was (i) a lower expression of VCAM1 in both materials, (ii) a higher expression of CCL4 in collagen scaffolds, and (iii) a lower expression of CXCR4 and MCL1 (transcript variant 2) in collagen scaffolds, while it was higher in a CMC-PEG gel. Hence, culture in the material can suppress the expression of a pro-apoptotic gene (MCL1 in collagen scaffolds) or replicate certain gene expression patterns attributed to CLL cells in lymphoid organs (low CXCR4, high CCL4 in collagen scaffolds) or blood (high CXCR4 in CMC-PEG).

• MeSH
• buněčné kultury metody   MeSH
• chronická lymfatická leukemie * patologie   metabolismus   MeSH
• gely chemie   MeSH
• kolagen * chemie   farmakologie   MeSH
• lidé MeSH
• polyethylenglykoly * chemie   MeSH
• receptory CXCR4 metabolismus   MeSH
• sodná sůl karboxymethylcelulosy * chemie   farmakologie   MeSH
• techniky 3D buněčné kultury metody   MeSH
• tkáňové podpůrné struktury * chemie   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Electrochemical Drilling (ECD) is an unconventional method aimed at creating holes in metallic workpieces characterized by high hardness and complex structures. This study analyzes the influence of process variables, including machining voltage, electrolyte concentration, electrode rotational speed, electrolyte flushing pressure, and workpiece material, on the novel hole performance index (HPI) in electrical discharge machining (ECD). The HPI was identified as a suitable metric for simultaneously evaluating hole geometry and drilling time across various machining parameters and workpiece materials. The analysis of variance (ANOVA) method was employed to determine the significance of each machining parameter and workpiece material on the HPI. The research employed signal-to-noise ratio analysis to identify the optimal machining parameters. The findings demonstrated that the workpiece material and machining voltage were significant factors influencing HPI. The validation tests demonstrated that the proposed statistical method can significantly reduce HPI.

• MeSH
• elektrochemické techniky * metody   MeSH
• elektrody MeSH
• poměr signál - šum MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Appendiceal mucocele, a rare condition characterized by mucoid material accumulation in the appendix, often presents asymptomatically. Diagnosis can be challenging, and surgical resection is crucial to prevent complications. We report a case managed in a low-resource setting, highlighting the importance of early identification. CASE PRESENTATION: A 56-year-old postmenopausal woman presented with right lower quadrant pain and a pelvic mass. Imaging revealed a cystic lesion and exploratory laparotomy was performed. Intraoperatively, a mucocele of the appendix was discovered. An appendectomy was performed, and a histopathological examination confirmed a serous borderline tumor, this work has been reported in line with the SCARE criteria. DISCUSSION: Preoperative diagnosis of appendiceal mucoceles is difficult due to their clinical variability. Surgical intervention is essential, with meticulous resection required to prevent peritoneal contamination. The absence of intraoperative pathology consultation in this case underscores the need for greater access to specialized resources, including pathology services, in resource-limited settings to ensure accurate diagnosis and appropriate surgical management. CONCLUSION: This case highlights the critical importance of clinical suspicion for appendiceal mucoceles, even when initial radiological findings are inconclusive. The lack of intraoperative pathology consultation underscores the need for specialized pathology services in resource-limited settings. Given the increased risk of colonic adenocarcinoma, multidisciplinary collaboration and diligent post-operative surveillance are crucial for optimizing patient outcomes.

• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

OBJECTIVES: Comparisons of material hardness may be affected by the indentation size effect (ISE), which is characterized by increasing hardness values at decreasing loads. This study aimed to assess the influence of load, dwell time and measurement method on ISE in dental resin-based composites with different filler content. METHODS: Knoop (HK) and Vickers (HV) microindentation hardness of Filtek Ultimate Universal Restorative (FU) and Filtek Supreme Flowable Restorative (FF) was measured under different loads (0.098-2.96 N, i.e. 10-300 gf) and dwell times (5-30 s). Their effects on HK and HV were evaluated using repeated measures ANOVA, which was also used to compare the measurement methods. Coefficients of Meyer's equation, proportional specimen resistance (PSR) model and a modified PSR model were calculated using regression analyses. RESULTS: ISE was more pronounced for the highly-filled FU than for the less-filled FF, and HK was more susceptible to ISE than HV. The effect of dwell time was similar for both materials and measurement methods; hardness values decreased with dwell time, significantly between 5 s and 30 s. SIGNIFICANCE: The possible presence of ISE should be considered when determining measurement conditions for the microindentation hardness of dental resin-based composites. HV was found to be less sensitive to ISE and provided stable hardness values at lower loads than HK. Due to the high variability of composites, any hardness measurement should be preceded by mapping the effect of load to ensure that load-independent hardness is measured. If hardness values continue to decrease in the whole range of increasing loads, load-independent hardness can be calculated using the PSR model.

• MeSH
• složené pryskyřice * chemie   MeSH
• testování materiálů * MeSH
• testy tvrdosti MeSH
• tvrdost * MeSH
• Publikační typ
• časopisecké články MeSH

Biotransformation of steroids by fungi has been raised as a successful, eco-friendly, and cost-effective biotechnological alternative for chemical derivatization. Endophytic fungi live inside vegetal tissues without causing damage to the host plant, making available unique enzymes that carry out uncommon reactions. Moreover, using nanofibrous membranes as support for immobilizing fungal cells is a powerful strategy to improve their performance by enabling the combined action of adsorption and transformation processes, along with increasing the stability of the fungal cell. In the present study, we report the use of polyacrylonitrile nanofibrous membrane (PAN NFM) produced by electrospinning as supporting material for immobilizing the endophytic fungus Penicillium citrinum H7 aiming the biotransformation of progesterone. The PAN@H7 NFM displayed a high progesterone transformation efficiency (above 90%). The investigation of the biotransformation pathway of progesterone allowed the putative structural characterization of its main fungal metabolite by GC-MS analysis. The oxidative potential of P. citrinum H7 was selective for the C-17 position of the steroidal nucleus.

• MeSH
• biotransformace MeSH
• nanovlákna * chemie   MeSH
• progesteron MeSH
• Publikační typ
• časopisecké články MeSH