Search Results (2,158)

Background/Objectives: Prostate cancer (PCa) remains a major global health issue, associated with significant mortality and morbidity. Despite advances in diagnosis and treatment, predicting biochemical recurrence (BCR) after radical prostatectomy remains challenging, highlighting the need for reliable biomarkers to guide prognosis and therapy. The study aimed to evaluate the prognostic significance of the PTEN and ERG biomarkers in predicting BCR and tumor progression in PCa patients who underwent radical prostatectomy. Methods: This study consisted of a cohort of 91 patients with localized PCa who underwent radical prostatectomy between 2016 and 2022. From this cohort, 77 patients were selected for final analysis. Tissue microarrays (TMAs) were constructed from paraffin blocks, and immunohistochemical (IHC) staining for PTEN and ERG was performed using specific antibodies on the Ventana BenchMark ULTRA system (Roche Diagnostics, Indianapolis, IN, USA). Stained sections were evaluated and correlated with clinical and pathological data. Results: PTEN expression showed a significant negative correlation with BCR (r = −0.301, p = 0.014), indicating that reduced PTEN expression is associated with increased recurrence risk. PTEN was not significantly linked to PSA levels, tumor stage, or lymph node involvement. ERG expression correlated positively with advanced pathological tumor stage (r = 0.315, p = 0.005) but was not associated with BCR or other clinical parameters. Conclusions: PTEN appears to be a valuable prognostic marker for recurrence in PCa, while ERG may indicate tumor progression. These findings support the potential integration of PTEN and ERG into clinical practice to enhance risk stratification and personalized treatment, warranting further validation in larger patient cohorts. Full article

Objectives: Facial soft tissue imaging is crucial in orthodontic treatment planning, and the structured light scanning technology found in the latest iPhone models constitutes a promising method. Currently, studies which evaluate the accuracy of smartphone-based three-dimensional (3D) facial scanners are scarce. This study compares smartphone scans with cone-beam computed tomography (CBCT) images. Materials and Methods: Three-dimensional images of 23 screened patients were captured with the camera of an iPhone 13 Pro Max and processed with the Scandy Pro application; CBCT scans were also taken as a standard of care. After establishing unique image pairs of the same patient, linear and angular measurements were compared between the images to assess the scanner’s two-dimensional trueness. Following the co-registration of the virtual models, a heat map was generated, and root mean square (RMS) deviations were calculated for quantitative assessment of 3D trueness. Precision was determined by comparing consecutive 3D facial scans of five participants, while intraobserver reliability was assessed by repeating measurements on five subjects after a two-week interval. Results: This study found no significant difference in soft tissue measurements between smartphone and CBCT images (p > 0.05). The mean absolute difference was 1.43 mm for the linear and 3.16° for the angular measurements. The mean RMS value was 1.47 mm. Intraobserver reliability and scanner precision were assessed, and the Intraclass Correlation Coefficients were found to be excellent. Conclusions: Smartphone facial scanners offer an accurate and reliable alternative to stereophotogrammetry systems, though clinicians should exercise caution when examining the lateral sections of those images due to inherent inaccuracies. Full article

Syphilis, which is caused by Treponema pallidum, remains one of the most common congenital infection worldwide and has tremendous consequences for the mother and her developing foetus if left untreated. The complexity of the exposure to this pathogen extends beyond the well-established clinical manifestations, as it can profoundly affect placental histomorphology. This study aimed to compare T. pallidum-exposed placental villi structures with healthy placentae at term to evaluate the histomorphological differences using stereology. In this case-control study conducted at term (38 weeks ± 2 weeks), 78 placentae were collected from the hospital delivery suites, comprising 39 cases (T. pallidum-exposed) and 39 controls (non-exposed), who were gestational age-matched with other potential confounders excluded. Blood samples from the umbilical vein and placental basal plate were tested for syphilis, using rapid diagnostic test (RDT) kits for T. pallidum (TP) antibodies (IgG and IgM) to classify placentae as exposed to T. pallidum (cases) and non-exposed (controls). Tissue sections were prepared and stained with haematoxylin and eosin, and the mean volume densities of syncytial knots, foetal capillaries, syncytial denuded areas, and intervillous spaces were estimated using stereological methods. Statistical analysis was performed to compare the mean values between the case and control groups. Stereological assessment revealed significant differences between the T. pallidum-exposed and non-exposed groups with regard to syncytial knots (p < 0.0001), syncytial denudation (p < 0.0001), and foetal capillaries (p < 0.0001), but no significant difference in the intervillous space was found (p = 0.1592). Therefore, our study shows, for the first time, that the histomorphology of human placental villi appears to be altered by exposure to T. pallidum. It will, therefore, be interesting to determine whether these changes in the placental villi translate into long-term effects on the baby. Full article

This study evaluates the influence of general anesthesia (GA) and spinal anesthesia (SA) on physiological and oxidative stress in parturients undergoing elective cesarean section, one of the most frequently performed surgical procedures worldwide. A total of 101 pregnant women were included, categorized into GA (n = 51) and SA (n = 50) groups. Blood samples were collected at three time points: one hour before surgery (Measurement 1), at umbilical cord clamping (Measurement 2), and two hours post-surgery (Measurement 3). Biomarkers of oxidative stress, complete blood count, and levels of biochemical parameters were measured. In second and/or third measurement, biochemical blood analysis showed increased prolactin and cortisol levels, followed by spike of glucose and insulin in the GA group. However, levels of tri-iodothyronine were reduced in both groups in the third measurement. Glutathione S-transferase (GST) activity was increased in both groups in third measurement. The results showed increased concentrations of total SH groups and decreased concentrations of non-protein SH groups in the GA group during Measurement 2. Lymphocyte count was found to be predictor of GST levels. The results indicate more a pronounced endocrine response in GA group and speak in favor of spinal anesthesia. Both kinds of anesthesia are equally safe in terms of the oxidative status of the tissue. Full article

Unionid mussel populations in a section of the Clinch River in Virginia, USA, has declined substantially, but the causes of the decline remain unknown. To investigate this zone of decline (ZOD), we deployed juvenile freshwater mussels (Villosa iris in 2012 and Lampsilis fasciola in 2013) in both cages and silos at sites within the Clinch River System. We analyzed mussel tissues for trace element and organic contaminant concentrations, shells for trace elements, and environmental media (total water, dissolved water, particulate sediment, and bedload sediment) for both inorganic and organic contaminants. We found a few differences between mussels deployed in cages and those deployed in silos: survival was slightly lower in cages due to periodic sedimentation. Our results identified the ZOD based on the accumulation of trace elements (notably As, Cu, Fe, Mn, Ni, and Sr), polycyclic aromatic hydrocarbons (PAHs), and δ¹⁵N enrichment, with especially high concentrations found in the human-impacted tributaries, Dumps Creek and Guest River. Some correlations were found between environmental media and both mussel tissues and shells. In particular, PAHs and Mn had several significant relationships between bioaccumulated concentrations and environmental concentrations. Finally, Co, Cu, Fe, and V in soft tissues negatively correlated with mussel growth, whereas bioaccumulated PAH concentrations correlated negatively with resident mussel densities. Full article

Background: It is estimated that in Italy, there were 364,000 new diagnoses of neoplasms each year and that the overall incidence of blood cancers was 10% of these. Leukemia and lymphomas represented the ninth and eighth places, respectively, among the causes of death from neoplasia. Hematopoietic stem cell transplantation represented an effective treatment option for many of these malignancies, and not only that: benign and congenital diseases could also be treated. Objective: To assess knowledge among the Apulian population regarding stem cell donation and factors that could influence this choice, focusing especially on the knowledge of the residents of Puglia, Italy on how stem cells were harvested and their functions, their reasons for joining the National Registry, and the reasons that hold them back from making such a choice. Study Design: An observational and cross-sectional study was conducted, through snowball sampling methodology, until data saturation. An online survey was conducted, which included several Italian associations. The questionnaire administered contained five main sections, such as sociodemographic data, knowledge of the existence of National Registries and their adherence, the nationwide presence of various associations that promote donation, knowledge with respect to the structure, use and functions of stem cells, sources of procurement, such as bone marrow, peripheral blood and umbilical cord, and related procedures, beliefs, attitudes, values, and opinions of the Italian population regarding the topic, and degree of information and education regarding bone marrow donation. Results: A total of 567 Apulian citizens were enrolled. Of these, 75.3% were female and 96.8% were aged between 18 and 65 years. Most of participants were single (46.9%) and married (47.3%) and had a diploma (44.4%), and less had a degree (35.8%). Significant differences were recorded between gender, singles, and married participants, and participants with a diploma or a degree and the items proposed. Conclusions: A true culture of donation in our region was not clearly spread. Although something has been accomplished in recent years in terms of deceased donor donation, still a great deal needs to be achieved for living donation, which encountered a great deal of resistance. It has been deemed necessary to seek winning solutions to this issue in terms of communication and information campaigns, raising awareness and empowering citizens to express consciously their concerns about organs and tissues and to stand in solidarity with those who suffered. Full article

Background and Clinical Significance: Gliomas diagnosed during pregnancy are rare, and there are no established guidelines for their management. Effective treatment requires a multidisciplinary approach to balance maternal health and pregnancy preservation. Case Presentation: We here present a case of rapidly progressing glioma in a 33-year-old pregnant woman. The patient initially presented with a generalized tonic–clonic seizure at 21 weeks’ gestation. Imaging revealed a tumor in the right cerebral lobe, involving both cortical and subcortical structures, while magnetic resonance spectroscopy suggested a low-grade glioma. The patient remained clinically stable for two months but then developed severe headaches; MRI showed a worsening mass effect. At 34 weeks’ gestation, an emergency and premature caesarean section was performed under general anesthesia. The patient then underwent a craniotomy for maximal tumor resection, which was histologically and molecularly diagnosed as IDH wild-type glioblastoma (GB). Using qPCR, we found that the GB tissue showed upregulated expression of genes involved in cell structure (GFAP, VIM) and immune response (SSP1, TSPO), as well as increased expression of genes related to potential hormone response (AR, CYP19A1, ESR1, GPER1). After surgery, the patient showed resistance to Stupp protocol therapy, which was substituted with lomustine and bevacizumab combination therapy. Conclusions: This case illustrates that glioma may progress rapidly during pregnancy, but a favorable obstetric outcome is achievable. Management of similar cases should respect both the need for timely treatment and the patient’s informed decision. Full article

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with low survival rates, especially in advanced stages, despite improved therapies. New developments show that immune checkpoint inhibitors (ICIs) are promising treatment options. A better understanding of immune suppression in OSCC could enable new therapeutic approaches and effective ICI combinations. Methods: The aim of this cross-sectional study was to investigate the significance of the differential expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD28 and their ligands CD80 and CD86 for the diagnosis and treatment of OSCC. To this end, mRNA expression was analysed by RT-PCR and compared in 65 healthy oral mucosa samples (NOM) and 104 OSCC samples. Results: The expression of CTLA-4 (a soluble and membrane-bound isoform) was increased in OSCC by 1.72-fold (p = 0.004) and 6.88-fold (p < 0.001), respectively. There was no significant difference for CD28 (p = 0.283), nor for the soluble isoform of CD86 (p = 0.845). The membrane isoform of CD86 was increased in OSCC by a factor of 1.39 (p = 0.009) and CD80 by 6.11-fold (p < 0.001). Conclusions: The results show a significant association between CTLA-4, CD80 and membrane-bound CD86 expression and diagnosis. They could improve diagnostics in multi-marker approaches and serve as therapeutic targets for ICI strategies. In particular, the data indicate a stronger immunosuppressive role of CD80 compared to CD86 in a tumor tissue context, suggesting the exploration of anti-CTLA-4 and anti-CD80 antibody combinations in animal models. Full article

The aim of this study was to determine whether a low dose of zearalenone (ZEN) affects the mRNA expression of the CYP1A1 (P450 cytochrome) and GSTπ1 (glutathione S-transferase) genes in the large intestine of pre-pubertal gilts. Materials: Control (C) group gilts (n = 18) received a placebo. Experimental (E) group gilts (n = 18) were orally administered 40 μg ZEN/kg body weight (BW) each day before morning feeding for 42 days. Three animals from each group were sacrificed each week of the study. Tissue samples were collected from the medial parts of the ascending colon and the descending colon on six dates. Results: Zearalenone concentrations were multiple times higher in the last three weeks of exposure, and ZEN metabolites were not detected. In phase I, CYP1A1 mRNA expression in the ascending colon was suppressed in the final three weeks of exposure, which substantially increased the ZEN concentration in the descending colon. In phase II, ZEN levels were high in the descending colon due to CYP1A1 suppression in the ascending colon. Consequently, the phase II detoxification processes could not take place due to the absence of a substrate. Conclusion: This study demonstrated that low-dose ZEN mycotoxicosis disrupts the expression of the CYP1A1 and GSTπ1 genes, which co-participate in the enzymatic biotransformation of ZEN in both examined sections of the large intestine. The above could have contributed to increased ZEN accumulation in the mucosa of the descending colon in the last three weeks of exposure. Full article

We developed a mathematical model to examine the scattering of radiation by a periodic structure of circular and elliptical microcavities formed in a planar optical waveguide. The waveguide simulates the behaviour of a 62.5/125 µm multimode optical fibre. The calculations focused on the intensity distribution of scattered light with a wavelength of 1310 nm along the periodic structure, i.e., along the side surface of the waveguide, as a function of the microcavity dimensions and their spatial arrangement within the waveguide core. The optimal geometrical parameters of the microstructure, ensuring the most uniform light scattering, were identified. The model is valid for multimode optical fibres containing strictly periodic structures of microcavities with spherical or elliptical cross-sections that scatter laser radiation in all directions. One potential application of such fibres is as light sources in medical probes for surgical procedures requiring additional illumination and uniform irradiation of affected tissues. Furthermore, the findings of this study offer significant potential for the development of sensing elements for fibre-optic sensors. The findings of this study will facilitate the design of scattering structures with microcavities that ensure a highly uniform scattering pattern. Full article

Background/Objectives: Early diagnosis of stroke is crucial for effective treatment with tissue plasminogen activator (tPA) and endovascular thrombectomy. Emergency medical services (EMSs) screening and the early activation of emergency department (ED) stroke protocols reduce treatment times and improve patient outcomes. This study aims to validate ED stroke protocol activation by EMSs in a large stroke center. Methods: This retrospective cross-sectional study was conducted at Magen David Adom and Shamir Medical Center between 1 January 2019 and 31 December 2019. Data were categorized into patients suspected by EMSs of having a stroke and those not suspected by EMSs but diagnosed as having a stroke in the ED. The primary outcome was the accuracy of EMSs in activating ED stroke protocols. Results: In this study, there were 23,061 patients, of which 11,841 (51.9%) were females. The mean age was 61.4 (SD = 22.72) years old. EMSs suspected 743 (3.22%) patients were having a stroke. In 587 (79%), EMSs activated ED stroke protocols. There were 88 cases where strokes were diagnosed in the ED when EMSs did not suspect a stroke. The overall EMSs negative predictive value (NPV) was 100% while the positive predictive value (PPV) was 20%. Conclusions: While Israeli EMSs over-activate the ED stroke protocol, stroke patients are almost never missed, achieving the goal of prehospital stroke screening. To prevent resource waste, all involved teams should be notified, and the actual activation of the stroke protocol should be carried out by an ED physician upon patient arrival. Communication between all levels regarding stroke protocol should also be increased to decrease the time to treatment. Full article

DNA is inherently unstable and is susceptible to damage from both endogenous sources (such as reactive oxygen species) and exogenous factors (including UV, ionizing radiation, and chemicals). The accumulation of DNA damage manifests as genetic mutations, chromosomal instability, and the stalling of DNA replication and transcription processes. Accumulated DNA damage influences apoptosis and cell cycle checkpoints, serving as one of the key triggers for the manifestation of the senescent phenotype. Both aging and cancer are associated with the accumulation of mutations in somatic cells. Disruption of cell cycle control and uncontrolled proliferation are fundamental characteristics of any cancer cell, with the majority of anticancer drugs acting as inhibitors of cyclin-dependent kinases, thereby inducing a transition of cells into a senescent state. Consequently, disturbances in the dynamics and regulation of inflammatory responses, oxidative stress, cell proliferation, DNA damage repair, and epigenetic anomalies, along with the influence of retroviruses and transposons, lead to the accumulation of senescent cells within the human body, characterized by blocked replication and cell cycle, as well as a distinct secretory phenotype. The age-related or disease-associated accumulation of these senescent cells significantly alters the physiology of tissues and the organism as a whole. Many secondary metabolites of higher plants exhibit senolytic and senomorphic activities, although most of them are not fully characterized. In this review, we will explore the principal signaling pathways in mammalian cells that govern the cell cycle and cellular senescence, with a particular emphasis on how their dynamics, expression, and regulation have been modified through the application of senotherapeutic compounds. The second section of the review will identify key target genes for the metabolic engineering, primarily aimed at enhancing the accumulation of plant secondary metabolites with potential therapeutic benefits. Lastly, we will discuss the rationale for utilizing liver cells as a model system to investigate the effects of senolytic compounds on human physiology and health, as well as how senotherapeutic substances can be leveraged to improve gene therapy approaches based on CRISPR/Cas9 and prime-editing technologies. Full article

Background: Liposarcoma (LPS) is a rare malignant tumor, but it is also one of the most common adult soft-tissue sarcomas. Myxoid liposarcoma (MLPS) accounts for 30% of all LPS cases. Diagnosis during pregnancy and the puerperium is very rarely reported, and only a few cases have been reported in the thigh. Case presentation: We report the case of a 36-year-old female patient on the 11th day of the puerperium after a cesarean section. The patient presented to the gynecology ward owing to the sudden appearance of a tumor in the medial part of her right thigh. The lesion was non-painful, mobile, soft, approximately 20 cm in diameter, and protruded above the level of the rest of the thigh surface. A suspicion of hematoma was raised. The final diagnosis was high-grade MLPS. Conclusions: An MLPS diagnosis is uncommon in female patients and even rarer during pregnancy. This case represents a novel occurrence, as the first instance in which symptoms manifested during the puerperium. Proper treatment and early detection could improve disease outcomes. Full article

Introduction: Unilateral cleft lip and palate (CLP) is a severe orofacial birth defect characterized by improper fusion of facial parts and disturbed orofacial functions. The defect manifests as a gap in the orofacial tissues that is accompanied by defective healing patterns and chronic inflammation. The immune system’s defense factors modulate immunity, inflammation, and healing. Angiogenesis factors control blood-vessel formation. Therefore, these factors are vital in the immunological assessment and understanding of CLP morphopathogenesis. The aim of the study is to assess the distribution of vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF- β1), the total macrophage population and the M2 subtype, heat-shock proteins (HSP) 60 and 70, and nuclear factor kappa B (NF-κB) p50 and p65 subtypes in the affected tissue of children with CLP before and during primary dentition. Materials and Methods: Tissue samples were obtained from 15 patients aged from 3 to 8 months during veloplastic surgery. Five controls were used for comparison of data. Immunohistochemistry, light microscopy, semi-quantitative evaluation (from 0 to ++++), and statistics (Mann–Whitney U test and Spearman’s rank correlation) were used to evaluate the data for statistically significant differences and correlations between the groups. Results: Epithelial tissues affected by CLP presented with statistically significant increases in levels of VEGF (p = 0.007), total macrophages (p = 0.007), HSP60 (p = 0.001), NF-κB p65 (p = 0.000), and p50 (p = 0.045), but with a decrease in M2 macrophages (p = 0.025). Blood vessels in CLP-affected tissues showed a statistically significant increase in levels of NF-κB p65 (p = 0.003) and a statistically significant decrease in M2 numbers (p = 0.014). Connective tissue presented with no statistically significant differences. Spearman’s rank correlation revealed multiple statistically significant correlations—26 positive and 5 negative. Conclusions: Statistically significant changes in levels of VEGF and both NF-κB subtypes and numbers of total macrophages and M2 macrophages suggest a possible alteration of variable immune and inflammatory reactions and macrophage functions associated with the initiation and maintenance of the chronic process and the resulting damage. Full article

Background/Objective: The Rs1 exon-1-del rat (Rs1KO) XLRS model shows normal retinal development until postnatal day 12 (P12) when small cystic spaces start to form in the inner nuclear layer. These enlarge rapidly, peak at P15, and then collapse by P19. These events overlap with eye opening at P12–P15. We investigated whether new light-driven retinal activity could contribute to the appearance and progression of schisis cavities in this rat model of XLRS disease. Methods: For dark rearing (D/D), mating pairs of Rs1KO strain were raised in total darkness in a special vivarium at UC Davis. When pups were born, they were maintained in total darkness, and eyes were collected at P12, P15, and P30 (n = 3/group) for each of the D/D and cyclic light-reared 12 h light–12 h dark (L/D) Rs1KO and wild-type (WT) littermates. Eyes were fixed, paraffin-embedded, and sectioned. Tissue morphology was examined by H&E and marker expression of retinoschisin1 (Rs1), rhodopsin (Rho), and postsynaptic protein 95 (Psd95) by fluorescent immunohistochemistry. H&E-stained images were analyzed with ImageJ version 1.54h to quantify cavity size using the “Analyze Particles” function. Results: Small intra-retinal schisis cavities begin to form by P12 in the inner retina of both D/D and L/D animals. Cavity formation was equivalent or more pronounced in D/D animals than in L/D animals. We compared Iba1 (activation marker of immune cells) distribution and found that by P12, when schisis appeared, Iba1⁺ cells had accumulated in regions of schisis. Iba1⁺ cells were more abundant in Rs1KO animals than WT animals and appeared slightly more prevalent in D/D- than L/D-reared Rs1KO animals. We compared photoreceptor development using Rho, Rs1, and Psd95 expression, and these were similar; however, the outer segments (OSs) of D/D animals with Rho labeling at P12 were longer than L/D animals. Conclusions: The results showed that cavities formed at the same time in D/D and L/D XLRS rat pups, indicating that the timing of schisis formation is not light stimulus-driven but rather appears to be a result of developmental events. Cavity size tended to be larger under dark-rearing conditions in D/D animals, which could be due to the decreased rate of phagocytosis by the RPE in the dark, allowing for continued growth of the OSs without the usual shedding of the distal tip, a key mechanism behind dark adaptation in the retina. These results highlight the complexity of XLRS pathology; however, we found no evidence that light-driven metabolic activity accounted for schisis cavity formation. Full article