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  • 1
    Online Resource
    Online Resource
    Novel Expression of Thymine Dimers in Renal Cell Carcinoma, Demonstrated through Immunohistochemistry
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 11 ( 2022-10-23), p. 2673-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 11 ( 2022-10-23), p. 2673-
    Abstract: Despite significant developments in renal cell carcinoma (RCC) detection and molecular pathology, mortality has been steadily rising. Advanced RCC remains an incurable disease. Better clinical management tools, i.e., RCC biomarkers, have yet to emerge. Thymine-dimers (TDs) were traditionally considered photo-dependent pre-mutagenic lesions, occurring exclusively during ultra-violet light exposure. Non-oxidative, direct, and preferential byproducts of DNA photochemical reactions, TDs, have recently shown evidence regarding UVR-independent formation. In this study, we investigate, for the first time, TD expression within RCC tumor tissue and tumor-adjacent healthy renal parenchyma using a TD-targeted IHC monoclonal antibody, clone KTM53. Remarkably, out of the 54 RCCs evaluated, 77.8% showed nuclear TD-expression in RCC tumor tissue and 37% in the tumor-adjacent healthy renal parenchyma. A comprehensive report regarding quantitative/qualitative TD-targeted immunostaining was elaborated. Two main distribution models for TD expression within RCC tumor tissue were identified. Statistical analysis showed significant yet moderate correlations regarding TD-positivity in RCC tissue/tumor-adjacent healthy renal parenchyma and TNM stage at diagnosis/lymphatic dissemination, respectively, indicating possible prognostic relevance. We review possible explanations for UVR-independent TD formation and molecular implications regarding RCC carcinogenesis. Further rigorous molecular analysis is required in order to fully comprehend/validate the biological significance of this newly documented TD expression in RCC.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10112673
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 2
    Online Resource
    Online Resource
    A Retrospective Assessment of Sputum Samples and Antimicrobial Resistance in COVID-19 Patients
    MDPI AG ; 2023
    In:  Pathogens Vol. 12, No. 4 ( 2023-04-19), p. 620-
    Details
    In: Pathogens, MDPI AG, Vol. 12, No. 4 ( 2023-04-19), p. 620-
    Abstract: Data on bacterial or fungal pathogens and their impact on the mortality rates of Western Romanian COVID-19 patients are scarce. As a result, the purpose of this research was to determine the prevalence of bacterial and fungal co- and superinfections in Western Romanian adults with COVID-19, hospitalized in in-ward settings during the second half of the pandemic, and its distribution according to sociodemographic and clinical conditions. The unicentric retrospective observational study was conducted on 407 eligible patients. Expectorate sputum was selected as the sampling technique followed by routine microbiological investigations. A total of 31.5% of samples tested positive for Pseudomonas aeruginosa, followed by 26.2% having co-infections with Klebsiella pneumoniae among patients admitted with COVID-19. The third most common Pathogenic bacteria identified in the sputum samples was Escherichia coli, followed by Acinetobacter baumannii in 9.3% of samples. Commensal human pathogens caused respiratory infections in 67 patients, the most prevalent being Streptococcus penumoniae, followed by methicillin-sensitive and methicillin-resistant Staphylococcus aureus. A total of 53.4% of sputum samples tested positive for Candida spp., followed by 41.1% of samples with Aspergillus spp. growth. The three groups with positive microbial growth on sputum cultures had an equally proportional distribution of patients admitted to the ICU, with an average of 30%, compared with only 17.3% among hospitalized COVID-19 patients with negative sputum cultures (p = 0.003). More than 80% of all positive samples showed multidrug resistance. The high prevalence of bacterial and fungal co-infections and superinfections in COVID-19 patients mandates for strict and effective antimicrobial stewardship and infection control policies.
    Type of Medium: Online Resource
    ISSN: 2076-0817
    URL: Article
    DOI: 10.3390/pathogens12040620
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2695572-6
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  • 3
    Online Resource
    Online Resource
    A New Electrode Design for Direct Bladder Wall Stimulation: A Pilot Minipig Study with Chronic Testing
    MDPI AG ; 2022
    In:  Applied Sciences Vol. 12, No. 3 ( 2022-01-22), p. 1149-
    Details
    In: Applied Sciences, MDPI AG, Vol. 12, No. 3 ( 2022-01-22), p. 1149-
    Abstract: (1) Aims: To test a newly designed helical-wire hook electrode implanted in the bladder wall to induce contraction and promote voiding. (2) Methods: In three minipigs with a created lesion of the sacral spinal cord, four electrodes were implanted in the bladder wall, ventral to the trigone. Stimulation tests were conducted initially in conscious pigs, and later after general anesthesia. (3) Results: Electrical stimulation in the conscious animals on postoperative days 4 and 7 at 40 Hz was limited to 10 mA, because of abdominal, leg, and anal contractions with animal discomfort; bladder contractions were not induced. Electrical stimulation on postoperative days 9 and 28 at 60 mA under anesthesia induced sustained vesical wall contractions with bladder pressure variations, but without voiding. Simultaneous abdominal contractions occurred, with strong leg and anal contractions. Subsequent stimulation with a single set of electrodes or at 20 Hz induced less vesical pressure response. At autopsy, the electrodes had not migrated, and extraction forces were high, at 7.9 ± 0.9 Newtons (n = 12). (4) Conclusions: Our 28-day study has confirmed the utility of the new electrode design, preventing migration from the bladder wall and making it suitable for long-term electrode implants.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app12031149
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704225-X
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  • 4
    Online Resource
    Online Resource
    Contemporary Biomarkers for Renal Transplantation: A Narrative Overview
    MDPI AG ; 2023
    In:  Journal of Personalized Medicine Vol. 13, No. 8 ( 2023-07-31), p. 1216-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 13, No. 8 ( 2023-07-31), p. 1216-
    Abstract: Renal transplantation (RT) is the preferred treatment for end-stage renal disease. However, clinical challenges persist, i.e., early detection of graft dysfunction, timely identification of rejection episodes, personalization of immunosuppressive therapy, and prediction of long-term graft survival. Biomarkers have emerged as valuable tools to address these challenges and revolutionize RT patient care. Our review synthesizes the existing scientific literature to highlight promising biomarkers, their biological characteristics, and their potential roles in enhancing clinical decision-making and patient outcomes. Emerging non-invasive biomarkers seemingly provide valuable insights into the immunopathology of nephron injury and allograft rejection. Moreover, we analyzed biomarkers with intra-nephron specificities, i.e., glomerular vs. tubular (proximal vs. distal), which can localize an injury in different nephron areas. Additionally, this paper provides a comprehensive analysis of the potential clinical applications of biomarkers in the prediction, detection, differential diagnosis and assessment of post-RT non-surgical allograft complications. Lastly, we focus on the pursuit of immune tolerance biomarkers, which aims to reclassify transplant recipients based on immune risk thresholds, guide personalized immunosuppression strategies, and ultimately identify patients for whom immunosuppression may safely be reduced. Further research, validation, standardization, and prospective studies are necessary to fully harness the clinical utility of RT biomarkers and guide the development of targeted therapies.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm13081216
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662248-8
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  • 5
    Online Resource
    Online Resource
    Rats, Neuregulins and Radical Prostatectomy: A Conceptual Overview
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 6 ( 2023-03-13), p. 2208-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 6 ( 2023-03-13), p. 2208-
    Abstract: In the contemporary era of early detection, with mostly curative initial treatment for prostate cancer (PC), mortality rates have significantly diminished. In addition, mean age at initial PC diagnosis has decreased. Despite technical advancements, the probability of erectile function (EF) recovery post radical prostatectomy (RP) has not significantly changed throughout the last decade. Due to virtually unavoidable intraoperative cavernous nerve (CN) lesions and operations with younger patients, post-RP erectile dysfunction (ED) has now begun affecting these younger patients. To address this pervasive limitation, a plethora of CN lesion animal model investigations have analyzed the use of systemic/local treatments for EF recovery post-RP. Most promisingly, neuregulins (NRGs) have demonstrated neurotrophic effects in both neurodegenerative disease and peripheral nerve injury models. Recently, glial growth factor 2 (GGF2) has demonstrated far superior, dose-dependent, neuroprotective/restorative effects in the CN injury rat model, as compared to previous therapeutic counterparts. Although potentially impactful, these initial findings remain limited and under-investigated. In an effort to aid clinicians, our paper reviews post-RP ED pathogenesis and currently available therapeutic tools. To stimulate further experimentation, a standardized preparation protocol and in-depth analysis of applications for the CN injury rat model is provided. Lastly, we report on NRGs, such as GGF2, and their potentially revolutionary clinical applications, in hopes of identifying relevant future research directions.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12062208
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 6
    Online Resource
    Online Resource
    Evaluating Established Roles, Future Perspectives and Methodological Heterogeneity for Wilms’ Tumor 1 (WT1) Antigen Detection in Adult Renal Cell Carcinoma, Using a Novel N-Terminus Targeted Antibody (Clone WT49)
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 4 ( 2022-04-15), p. 912-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 4 ( 2022-04-15), p. 912-
    Abstract: Renal cell carcinoma (RCC) is arguably the deadliest form of genitourinary malignancy and is nowadays viewed as a heterogeneous series of cancers, with the same origin but fundamentally different metabolisms and clinical behaviors. Immunohistochemistry (IHC) is increasingly necessary for RCC subtyping and definitive diagnosis. WT1 is a complex gene involved in carcinogenesis. To address reporting heterogeneity and WT1 IHC standardization, we used a recent N-terminus targeted monoclonal antibody (clone WT49) to evaluate WT1 protein expression in 56 adult RCC (aRCC) cases. This is the largest WT1 IHC investigation focusing exclusively on aRCCs and the first report on clone WT49 staining in aRCCs. We found seven (12.5%) positive cases, all clear cell RCCs, showing exclusively nuclear staining for WT1. We did not disregard cytoplasmic staining in any of the negative cases. Extratumoral fibroblasts, connecting tubules and intratumoral endothelial cells showed the same exclusively nuclear WT1 staining pattern. We reviewed WT1 expression patterns in aRCCs and the possible explanatory underlying metabolomics. For now, WT1 protein expression in aRCCs is insufficiently investigated, with significant discrepancies in the little data reported. Emerging WT1-targeted RCC immunotherapy will require adequate case selection and sustained efforts to standardize the quantification of tumor-associated antigens for aRCC and its many subtypes.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10040912
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 7
    Online Resource
    Online Resource
    Contemporary Clinical Definitions, Differential Diagnosis, and Novel Predictive Tools for Renal Cell Carcinoma
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 11 ( 2022-11-14), p. 2926-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 11 ( 2022-11-14), p. 2926-
    Abstract: Despite significant progress regarding clinical detection/imaging evaluation modalities and genetic/molecular characterization of pathogenesis, advanced renal cell carcinoma (RCC) remains an incurable disease and overall RCC mortality has been steadily rising for decades. Concomitantly, clinical definitions have been greatly nuanced and refined. RCCs are currently viewed as a heterogeneous series of cancers, with the same anatomical origin, but fundamentally different metabolisms and clinical behaviors. Thus, RCC pathological diagnosis/subtyping guidelines have become increasingly intricate and cumbersome, routinely requiring ancillary studies, mainly immunohistochemistry. Meanwhile, RCC-associated-antigen targeted systemic therapy has been greatly diversified and emerging, novel clinical applications for RCC immunotherapy have already reported significant survival benefits, at least in the adjuvant setting. Even so, systemically disseminated RCCs still associate very poor clinical outcomes, with currently available therapeutic modalities only being able to prolong survival. In lack of a definitive cure for advanced RCCs, integration of the amounting scientific knowledge regarding RCC pathogenesis into RCC clinical management has been paramount for improving patient outcomes. The current review aims to offer an integrative perspective regarding contemporary RCC clinical definitions, proper RCC clinical work-up at initial diagnosis (semiology and multimodal imaging), RCC pathological evaluation, differential diagnosis/subtyping protocols, and novel clinical tools for RCC screening, risk stratification and therapeutic response prediction.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10112926
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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