Immunotherapy Applications for Thymine Dimers and WT1 Antigen in Renal Cancers: A Comparative Statistical Analysis.

Renal cell carcinoma (RCC) remains incurable in advanced stages. Biomarkers have proven to be quite useful in cancer therapeutics. Herein, we provide a comparative/integrative statistical analysis of seminal immunohistochemistry (IHC) findings for Wilms' Tumor 1 antigen (WT1) and thymine dimers (TDs), emerging as atypical, yet promising, potential biomarkers for RCCs. We assessed WT1/TD reactivity in adult RCC tumor cells, tumor microenvironment (TME), and tumor-adjacent healthy renal tissue (HRT). WT1 positivity was scarce and strictly nuclear in tumor cells, whereas TD-reactive tumor tissues were prevalent. We report statistically significant positive correlations between the density of reactive RCC cellularity and the intensity of nuclear staining for both biomarkers (WT1 - rho = 0.341, p-value = 0.036; TDs - rho = 0.379, p-value = 0.002). RCC stromal TME TD-positivity was much more frequent than WT1 reactivity, apparently proportional to that of the proper RCC cellularity and facilitated by extensive RCC inflammatory infiltration. TDs exhibited nuclear reactivity for most TME cell lines, while RCC TME WT1 expression was rare and inconsistent. In HRTs, TDs were entirely restricted to renal tubular cells, the likely cellular progenitor of most conventional RCC subtypes. In lieu of proper validation, these early findings have significant implications regarding the origins/biology of RCCs and may inform RCC therapeutics, both accounting for the high frequency of immunotherapy-permissive frameshift indels in RCCs, but also hinting at novel predictive clinical tools for WT1-targeted immunotherapy. Overall, the current study represents a meek yet hopefully significant step towards understanding the molecular biology and potential therapeutic targets of RCCs.

High Intraepithelial Mast Cell Density in Warthin's Tumor.

BACKGROUND/AIM: Warthin's tumor, the second most frequent neoplasia of the parotid gland, is characterized by a proliferation of both epithelial and lymphoid components. In addition to epithelial and lymphoid cells, various other cell types are implicated to varying degrees in the immune response. Notably, mast cells have long been recognized as a consistent cell population within this tumor. Despite the historical acknowledgment of mast cell presence, their true distribution and significance within Warthin's tumor remain unclear. In this study, we aimed to elucidate the distribution and significance of mast cells in Warthin's tumor. MATERIALS AND METHODS: Histochemical and immunohistochemical methods were employed for the evaluation of mast cells within tumor specimens. RESULTS: Our study revealed a notable concentration of mast cells in the epithelial component of Warthin's tumor. Microscopic examination showed predominant lymphoid and epithelial elements with occasional cystic formations. Immunohistochemical analysis identified mast cells in both components, emphasizing their role in the tumor microenvironment. Double immunostaining (mast cell tryptase and CD34) revealed no significant correlation between mast cells and blood vessels. Intraepithelial mast cells (IEMCs) had a significantly higher density in the epithelial component, suggesting a potential association with the tumor's benign nature. The relationship between IEMCs and epithelial cells, especially in the presence of cystic structures, offers valuable insights into the unique features of Warthin's tumor. CONCLUSION: Our study contributes to the understanding of mast cells in Warthin's tumor, highlighting a substantial concentration within the epithelial component. This knowledge may pave the way for further investigations into the roles of mast cells in the pathogenesis and treatment of Warthin's tumor.

Bacterial Species Involved in Venous Leg Ulcer Infections and Their Sensitivity to Antibiotherapy-An Alarm Signal Regarding the Seriousness of Chronic Venous Insufficiency C6 Stage and Its Need for Prompt Treatment.

BACKGROUND: Venous leg ulcers (VLUs) are a common chronic wound condition susceptible to infection by various bacterial species. Understanding bacterial presence and antibiotic sensitivity is crucial for effective treatment. Methodsː Medical records of 60 patients diagnosed with the C6 chronic venous insufficiency stage were analyzed retrospectively. The patients were divided into an active recurrent VLU group (33 cases) and a first-onset active VLU group (27 cases). Bacterial identification, antibiotic sensitivity, and laboratory markers were assessed. Resultsː Pseudomonas aeruginosa was the most prevalent bacterial species in both the study (72.72%) and control (37.03%) groups, along with other common bacteria such as Proteus mirabilis, Enterococcus sp., Staphylococcus aureus, Acinetobacter baumannii, Klebsiella spp., and Escherichia coli. Furthermore, uncommon bacteria, including Providencia rettgeri, Group B Streptococcus, and Salmonella Paratyphi B, and a fungal infection with Candida albicans, were identified only in the study group, while Morganella morganii was found exclusively in the control group. Pseudomonas aeruginosa showed significant sensitivity to several antibiotics, particularly Amikacin and Meropenem. Nonspecific laboratory markers, such as CRP, fibrinogen, ESR, WBC, CK, neutrophils, and lymphocytes, revealed statistically significant differences between groups, indicating their potential as biomarkers for monitoring recurrent VLUs. Conclusionsː These results highlight the need for comprehensive diagnostic approaches to effectively manage VLU infections and improve patient outcomes. Further research is warranted to explore factors influencing the presence of uncommon bacteria and to develop targeted interventions for VLU management.

Cryostripping Versus Conventional Safenectomy in Chronic Venous Disease Treatment: A Single Center Retrospective Cohort Study.

AIM: This study presents a comparative analysis of cryostripping to conventional saphenectomy. Materials and Methods: The study included 2191 patients admitted in the Phlebology Department, 1st Surgical Department, Emergency County Hospital Timisoara, between September 2013 and April 2023, between September 2013 and April 2023, who underwent saphenectomy by cryostripping (1327 patients) or conventionally (864 patients). We compared the duration and costs of the procedure, hospitalization period, post-operative results, method feasibility, as well as the technical advantages of cryostripping compared to conventional surgery. Results: A smaller proximal incision, compared to the classic operation, as well the fact that distal counter incision is not necessary, represents technical advantages of this procedure. Average duration of the intervention was 41 +- 12.8 minutes, consumables costs were about 52 +- 10 EUR/intervention, with an average hospitalization period was 1.05 +- 0.41 days. The post-operative results were favourable, early complications rate being reduced (ecchymoses Phi; 2 cm - 33.23%; hematoma - 2.11%; deep vein thrombosis - 0.15%; transient paresthesias 3.01%). Compared to classic saphenectomy, the costs of consumables/intervention are similar, intervention time, hospitalization period and complication rate being statistically significantly lower. An advantage of the method is the fact that the cryo-probes can be sterilized, being reusable; from the economic point of view, the technique perfectly fits in both public hospitals and private clinics. Conclusions: Cryostripping is a radical surgical procedure which bring a significant number of advantages compared to the classic saphenectomy, being an effective alternative in CVD treatment.

Exploring the transformative power of dance: A scoping review of dance interventions for adults with intellectual disabilities.

The aim of this scoping literature review (SCR) was to analyze the impact of dance on adults with intellectual disabilities, specifically examining its influence on their mobility, interpersonal relationships, well-being, and overall quality of life. A total of 15 papers were reviewed in order to explore the effects of dance on the well-being and quality of life of adults with intellectual disabilities. The findings indicated significant improvements in body awareness, increased engagement in physical activity, and enhanced mental health. This SCR demonstrates that dance is an effective means of facilitating social interaction among adults with intellectual disabilities, both with their therapists and family members. Additionally, the review uncovered valuable data on dance therapy programs designed for adults with intellectual disabilities, highlighting their potential to promote physical activity and reduce stress levels.

The Cavernous Nerve Injury Rat Model: A Pictorial Essay on Post-Radical Prostatectomy Erectile Dysfunction Research.

Understanding and addressing post-radical prostatectomy (RP) erectile dysfunction (ED) is of paramount importance for clinicians. Cavernous nerve (CN) injury rat model studies have provided consistently promising experimental data regarding regaining erectile function (EF) after nerve damage-induced ED. However, these findings have failed to translate efficiently into clinical practice, with post-RP ED therapeutic management remaining cumbersome and enigmatic. This disparity highlights the need for further standardization and optimization of the elaborate surgical preparation protocols and multifaceted reporting parameters involved in reliable CN injury rat model experimentation. Even so, despite its technical complexity, this animal model remains instrumental in exploring the functional implications of RP, i.e., surgical lesions of the neurovascular bundles (NVBs). Herein, besides cavernous nerve (CN) dissection, injury, and electrostimulation, multiple pressure measurements, i.e., mean arterial pressure (MAP) and intra-cavernosal pressure (ICP), must also be achieved. A transverse cervical incision allows for carotid artery cannulation and MAP measurements. Conversely, ICP measurements entail circumcising the penis, exposing the ischiocavernous muscle, and inserting a needle into the corporal body. Finally, using an abdominal incision, the prostate is revealed, and the major pelvic ganglia (MPG) and CNs are dissected bilaterally. Specific surgical techniques are used to induce CN injuries. Herein, we provide a narrative and illustrative overview regarding these complex experimental procedures and their particular requirements, reflecting on current evidence and future research perspectives.

Vascular Endothelial Growth Factor Family and Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a common cancer characterized by increased angiogenesis. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and has not been extensively studied in HNSCC. This review aimed to provide a comprehensive overview of the VEGF family and its involvement in HNSCC. It discusses the significance of angiogenesis in HNSCC and the potential implications of VEGF family members, including VEGF-A, VEGF-B, VEGF-C, and VEGF-D, in tumor progression and angiogenic processes. The review highlights the need for further investigation to elucidate the specific functions and therapeutic implications of the VEGF family in HNSCC, which can ultimately contribute to development of novel therapeutic strategies for this type of cancer.

Can Routine Laboratory Tests Be Suggestive in Determining Suspicions of Malignancy in the Case of Thyroid Nodules?

Background and objectives: Thyroid nodules are a common finding in clinical practice and can be either benign or malignant. The aim of this study was to compare laboratory parameters between patients with malignant thyroid nodules and those with benign thyroid nodules. Materials and methods: A total of 845 patients were included, with 251 in the study group (malignant thyroid nodules) and 594 in the control group (benign thyroid nodules). Results: Our results show that there were statistically significant differences in several laboratory parameters, including FT3, FT4, ESR, fibrinogen, WBC, and lymphocyte percentage, between the two patient groups (p < 0.05). Conclusions: These findings suggest that certain laboratory parameters may be useful in differentiating between benign and malignant thyroid nodules and could aid in the diagnosis and treatment of thyroid cancer. However, further diagnostic tests such as fine-needle aspiration biopsy and imaging studies are typically required for an accurate diagnosis. Routine laboratory tests prove most effective when combined with other diagnostic methods to identify thyroid cancer. Although not conclusive on their own, these tests significantly suggest and guide physicians to suspect malignancy in thyroid nodules. This affirmative answer to our question, "Can routine laboratory tests be suggestive in determining suspicions of malignancy in the case of thyroid nodules?" aligns with the results of our study.

Subglottotracheal Adenoid Cystic Carcinoma in a 16-Year-Old Female-A Case Report.

Cystic adenoid carcinoma (ACC) is a rare malignant epithelial tumor arising from exocrine glands and accounts for only 1% of head and neck cancers. ACCs are common in the fifth and sixth decades of life, predominantly in women, and characterized by slow progression, local aggression, recurrence, and high metastasis. Subglottotracheal ACC is a rare tumor in the pediatric population, with only a few cases reported in the literature. We present a case of a 16-year-old female who was diagnosed with ACC in the subglottic and tracheal region. The patient presented with respiratory failure but without a history of dysphonia, dyspnea, stridor, or dysphagia. The diagnosis was confirmed by a biopsy, and subsequent imaging studies showed a large tumor involving the subglottic and tracheal region. The therapeutic management of this patient has been challenging due to the rarity of this tumor in the pediatric population and the potential long-term complications associated with tumor recurrence and psychological impact. This case highlights the diagnostic and therapeutic challenges in the management of subglottotracheal ACC in children and the importance of a multidisciplinary approach to optimize patient outcomes.

Female Gonadal Venous Insufficiency in a Clinical Presentation Which Suggested an Acute Abdomen-A Case Report and Literature Review.

Pelvic venous insufficiency (PVI) is frequently associated with symptoms of abdominal pain or discomfort that is overlooked or under-diagnosed in women. Despite the fact that pelvic venous insufficiency in men is very well documented, its occurrence in women needs to be further studied. Patients with pelvic varicose veins undergo a long and inconclusive diagnostic work-up before the exact cause of the symptoms is identified. Gonadal venous insufficiency (GVI) is a condition that can present acutely, leading to diagnostic challenges. We present a case report of a 47-year-old female with acute abdominal pain and GVI, where endovascular embolization was used for successful treatment. The patient was diagnosed with GVI based on imaging findings of an enlarged left ovarian vein with retrograde flow and dilated pelvic veins seen on magnetic resonance imaging (MRI) with contrast material. Due to the severity of her symptoms and imaging findings, endovascular embolization was chosen as the treatment modality. The embolization was successful, and the patient's symptoms resolved completely. This case highlights the challenge of diagnosing GVI with acute clinical expression and the potential benefits of endovascular embolization as a treatment option. Further studies are needed to determine the optimal management strategies for acute GVI, but endovascular embolization should be considered a safe and effective option. At the same time, we present a short review of the recent literature data related to this topic.

Measuring the Quality of Life in Patients with Chronic Venous Disease before and Short Term after Surgical Treatment-A Comparison between Different Open Surgical Procedures.

Chronic venous disease (CVD) is a common pathology that significantly affects the quality of life (QoL) of patients. Methods: QoL was assessed in 317 patients diagnosed with CVD who underwent surgeries, including cryostripping (n = 113), high ligation and stripping (HL&S, n = 96), and phlebectomies (n = 108). CVD symptoms and QoL were assessed before surgery and 2 weeks after surgery using the following questionnaires: CIVIQ-20, VAS, Eq-5D, PHQ-9 and GAD-9. Results. The results reveal a significant correlation (p < 0.05) between CEAP score and QoL questionnaires performed preoperatively and postoperatively in all three surgical technique groups, with a statistical improvement postoperatively. Phlebectomy had the best postoperative QoL score (r = 0.495) compared to the other two types of procedures. Conclusions: Analyzing patients' subjective perception following conventional surgery for CVD treatment, an improved QoL is observed both in functional and psychosocial aspects, even early postoperatively. Classical surgical procedures remain an effective and feasible option in CVD treatment.

Profile and Potential Significance of Dendritic Cells in Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: The aim of the study was the analysis of immunohistochemical expression of S100 protein and CD1a by dendritic cells (DCs) from head and neck squamous cell carcinoma (HNSCC), correlation with the histological grade, as well as analysis of the potential significance of antigen-presenting cells according to tumor location. PATIENTS AND METHODS: Samples were collected from 50 patients with HNSCC, conventionally stained with hematoxylin and eosin for pathological diagnosis and grade, followed by immunohistochemical evaluation with S100 protein and CD1a expression. RESULTS: The correlation of S100 expression in DCs with histological grading was significant (p=0.049). We also observed a correlation between CD1a expression and histological grading (p=0.016). DCs density was predominantly intratumoral for both CD1a (63% of cases) and S100 protein expression (25% of cases). CONCLUSION: Our results demonstrated the association of DCs with histological grade. Their intratumoral infiltration suggests their potential antitumor role.

The mast cell reaction in premalignant and malignant lesions of the head and neck.

Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent and aggressive neoplasms of this anatomical region. Many studies evaluated the neoplastic cells, but few works focused on the tumor microenvironment. In the present study, we investigated the distribution and mast cell density (MCD) in malignant and premalignant lesions of the oral cavity, tongue, pharynx, and larynx. There were analyzed 52 specimens of HNSCC, and 15 biopsies taken from patients with dysplasia. Results were compared with those found in a control group of 10 biopsies of oral mucosa from patients with inflammatory diseases. Slides stained with Hematoxylin-Eosin were used for the histopathological diagnosis and grade, and mast cells (MCs) were identified by immunohistochemistry, using anti-MC tryptase. MCs were counted using a method similar to that proposed for microvessel density. We found a significant increase in the number of MCs from the normal oral mucosa until overt carcinoma. Unlike normal tissues, in HNSCC, many MCs were found between tumor cells. We found no relationship between MCs and blood vessels in the tumor area. A significant statistical correlation was found between dysplastic and malignant tumors, but not between tumors with a different grade. Also, it was not found relationship between MCD and the anatomical location of the tumor. Based on these results, we believe that MCD evaluated by anti-MC tryptase is an independent factor of prognosis and reflects an unfavorable outcome.

Proliferating Lymphatic Endothelial Cells as a Prognostic Marker in Head and Neck Squamous Cell Carcinoma.

Podoplanin and Ki-67 are two important markers of cancer progression. The aim of this study is to evaluate double immunostaining for Ki-67 and podoplanin in head and neck squamous cell carcinoma (HNSCC), and to observe the involvement of lymphagiogenesis in tumoral and peritumoral areas, as well as the density of tumor proliferation correlated with histopathological grading. A total of 50 patients with HNSCC were included in this study. We carried out a morphological evaluation of tissue samples, after that, cases were selected for double Ki-67 and podoplanin immunostaining. Podoplanin expression was significantly correlated with histopathological grade (p < 0.05; p = 0.037) and expression of Ki-67 (p < 0.05; p = 0.050). A high expression of podoplanin, as well as of the proliferation factor Ki-67, was observed in histopathological grade G3 and the correlation between these (p < 0.05; p = 0.028), and implication of LMVD and LVI was not significant (LMVD p = 0.577; LVI p = 0.976). This study demonstrated the importance of double immunolabeling in assessing lymphagiogenesis and tumor proliferation in correlation with histopathological grades in HNSCC.

Loss of E-Cadherin Expression Correlates With Ki-67 in Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: The aim of the study was to evaluate the correlation between the rate of proliferation and immunohistochemical expression of E-cadherin, and their predictive role in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Samples were collected from 50 patients with HNSCC, and the expression of Ki-67 and E-cadherin was evaluated by immunohisto-chemistry (IHC). Previously, samples were conventionally stained with haematoxylin and eosin for histological diagnosis and grade. RESULTS: High E-cadherin expression was predominantly associated with less differentiated tumours (p<0.5; p=0.0305). Also, we observed a significant correlation between Ki-67 expression in tumour cells and tumour grade (p=0.0245). A strong correlation was noticed between low E-cadherin expression, increased Ki-67-proliferation rate and advanced T2-T3 tumour stage (p=0.0242). CONCLUSION: In this study we showed that Ki-67 proliferation rate and E-cadherin expression are important features in patients with HNSCC. Therefore, higher Ki-67 index values correlate with loss of E-cadherin expression, which indicates a poorer prognosis. These aspects support the use of both Ki-67 and E-cadherin as prognostic markers in specimens from patients with HNSCC.

Biodiversity Patterns and Ecological Preferences of the Photobionts Associated With the Lichen-Forming Genus Parmelia.

The worldwide, ecologically relevant lichen-forming genus Parmelia currently includes 41 accepted species, of which the Parmelia sulcata group (PSULgp) and the Parmelia saxatilis group (PSAXgp) have received considerable attention over recent decades; however, phycobiont diversity is poorly known in Parmelia s. lat. Here, we studied the diversity of Trebouxia microalgae associated with 159 thalli collected from 30 locations, including nine Parmelia spp.: P. barrenoae, P. encryptata, P. ernstiae, P. mayi, P. omphalodes, P. saxatilis, P. serrana, P. submontana, and P. sulcata. The mycobionts were studied by carrying out phylogenetic analyses of the nrITS. Microalgae genetic diversity was examined by using both nrITS and LSU rDNA markers. To evaluate putative species boundaries, three DNA species delimitation analyses were performed on Trebouxia and Parmelia. All analyses clustered the mycobionts into two main groups: PSULgp and PSAXgp. Species delimitation identified 13 fungal and 15 algal species-level lineages. To identify patterns in specificity and selectivity, the diversity and abundance of the phycobionts were identified for each Parmelia species. High specificity of each Parmelia group for a given Trebouxia clade was observed; PSULgp associated only with clade I and PSAXgp with clade S. However, the degree of specificity is different within each group, since the PSAXgp mycobionts were less specific and associated with 12 Trebouxia spp., meanwhile those of PSULgp interacted only with three Trebouxia spp. Variation-partitioning analyses were conducted to detect the relative contributions of climate, geography, and symbiotic partner to phycobiont and mycobiont distribution patterns. Both analyses explained unexpectedly high portions of variability (99 and 98%) and revealed strong correlations between the fungal and algal diversity. Network analysis discriminated seven ecological clusters. Even though climatic conditions explained the largest proportion of the variation among these clusters, they seemed to show indifference relative to climatic parameters. However, the cluster formed by P. saxatilis A/P. saxatilis B/Trebouxia sp. 2/Trebouxia sp. S02/Trebouxia sp. 3A was identified to prefer cold-temperate as well as humid summer environments.

Metabolic Adaptations of CD4+ T Cells in Inflammatory Disease.

A controlled and self-limiting inflammatory reaction generally results in removal of the injurious agent and repair of the damaged tissue. However, in chronic inflammation, immune responses become dysregulated and prolonged, leading to tissue destruction. The role of metabolic reprogramming in orchestrating appropriate immune responses has gained increasing attention in recent years. Proliferation and differentiation of the T cell subsets that are needed to address homeostatic imbalance is accompanied by a series of metabolic adaptations, as T cells traveling from nutrient-rich secondary lymphoid tissues to sites of inflammation experience a dramatic shift in microenvironment conditions. How T cells integrate information about the local environment, such as nutrient availability or oxygen levels, and transfer these signals to functional pathways remains to be fully understood. In this review, we discuss how distinct subsets of CD4+ T cells metabolically adapt to the conditions of inflammation and whether these insights may pave the way to new treatments for human inflammatory diseases.

OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism.

Lactation is associated with increased bone turnover and rapid bone loss, which liberates skeletal calcium used for milk production. Previous studies suggested that an increase in the skeletal expression of receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand (RANKL) coupled with a decrease in osteoprotegerin (OPG) levels likely triggered bone loss during lactation. In this study, we treated lactating mice with recombinant OPG to determine whether bone loss during lactation was dependent on RANKL signaling and whether resorption of the maternal skeleton was required to support milk production. OPG treatment lowered bone resorption rates and completely prevented bone loss during lactation but, surprisingly, did not decrease osteoclast numbers. In contrast, OPG was quite effective at lowering osteoblast numbers and inhibiting bone formation in lactating mice. Furthermore, treatment with OPG during lactation prevented the usual anabolic response associated with reversal of lactational bone loss after weaning. Preventing bone loss had no appreciable effect on milk production, milk calcium levels, or maternal calcium homeostasis when mice were on a standard diet. However, when dietary calcium was restricted, treatment with OPG caused maternal hypocalcemia, maternal death, and decreased milk production. These studies demonstrate that RANKL signaling is a requirement for bone loss during lactation, and suggest that osteoclast activity may be required to increase osteoblast numbers during lactation in preparation for the recovery of bone mass after weaning. These data also demonstrate that maternal bone loss is not absolutely required to supply calcium for milk production unless dietary calcium intake is inadequate.