Machine learning-based classification of varicocoele grading: A promising approach for diagnosis and treatment optimization.

BACKGROUND: Varicocoele is a correctable cause of male infertility. Although physical examination is still being used in diagnosis and grading, it gives conflicting results when compared to ultrasonography-based varicocoele grading. OBJECTIVES: We aimed to develop a multi-class machine learning model for the grading of varicocoeles based on ultrasonographic measurements. METHOD: Between January and May 2024, we enrolled unilateral varicocoele patients at an infertility clinic, assessing their varicocoele stages using the Dubin and Amelar system. We measured vascular diameter and reflux time at the testicular apex and the subinguinal region ultrasonography in both the supine and standing positions. Using these measurements, we developed four multi-class machine learning models, evaluating their performance metrics and determining which patient position and projection were most influential in varicocoele grading. RESULTS: We included 248 patients with unilateral varicocoele in the study, their average age was 26.61 ± 4.95 years old. Of these, 212 had left-sided and 36 had right-sided varicocoeles. According to the Dubin and Amelar system, there were 66 grade I, 96 grade II, and 86 grade III varicocoeles. Among the models we created, the random forest (RF) model performed best, with an overall accuracy of 0.81 ± 0.06, an F1 score of 0.79 ± 0.02, a sensitivity of 0.69 ± 0.02, and a specificity of 0.8 ± 0.03. Vascular diameter measurement at the testicular apex in the supine position had the most impact on grading across all models. In support vector machine and multi-layer perceptron models, reflux time measurements from the subinguinal projection in the standing position contributed the most, while in RF and k-nearest neighbors models, measurements from the subinguinal projection in the supine position were the most influential. CONCLUSIONS: Machine learning methods have demonstrated superior accuracy in predicting disease compared to traditional statistical regressions and nomograms. These advancements hold promise for clinically automated prediction of varicocoele grades in patients. Tailored varicocoele grading for individuals has the potential to enhance treatment effectiveness and overall quality of life.

Exploring the impact of sexual positions on ejaculation: Insights from a survey study by the Andrology Working Group of the Society of Urological Surgery in Turkey.

BACKGROUND: Sexual position is one of the several aspects that affects ejaculation control, which is essential for sexual pleasure. Still little is known, nevertheless, about the connection between sexual positions and ejaculation duration. OBJECTIVE: To investigate the impact of various sexual positions on the duration of ejaculation and gain a deeper understanding of the elements that influence the ability to control ejaculation. METHOD: An online survey was carried out on a sample of 1904 heterosexual men between the ages of 18-65 years. Premature ejaculation (PE) diagnostic tool was used to define PE. Demographic, behavioral, and physiological traits that are linked to PE and non-PE groups were collected. The participants listed their preferred sexual positions and the ones they changed to during ejaculating. Also, analyses were performed between male/female active or deep/shallow thrust positions and PE status. RESULTS: Although there were no appreciable variations in age or circumcision between PE and non-PE groups, the age of first sexual experience was associated with PE status. Groups also varied in the number of weekly ejaculations, the duration of the favored ejaculations, and the characteristics of the erection. The most preferred sexual posture was the doggy style regardless of the group. When the non-PE group felt to ejaculate, they preferred to change the position significantly more than the PE group (74% vs 67.2%; p < 0.05). However, when participants felt ejaculate, non-PE participants tended to switch to shallow thrusting positions significantly more than PE participants, who preferred deeper positions (27.1% vs. 18%; p < 0.05). CONCLUSION: This study underlines the relevance of considering sexual positions in controlling PE. Modifying positions during sexual intercourse may offer a non-pharmacological therapeutic alternative for improving ejaculation control. Future studies in this field might help to create tailored PE treatment strategies.

Navigating the gray zone: Machine learning can differentiate malignancy in PI-RADS 3 lesions.

INTRODUCTION: The objective of this study is to predict the probability of prostate cancer in PI-RADS 3 lesions using machine learning methods that incorporate clinical and mpMRI parameters. METHODS: The study included patients who had PI-RADS 3 lesions detected on mpMRI and underwent fusion biopsy between January 2020 and January 2024. Radiological parameters (Apparent diffusion coefficient (ADC), tumour ADC/contralateral ADC ratio, Ktrans value, periprostatic adipose tissue thickness, lesion size, prostate volume) and clinical parameters (age, body mass index, total prostate specific antigen, free PSA, PSA density, systemic inflammatory index, neutrophil-lymphocyte ratio [NLR], platelet lymphocyte ratio, lymphocyte monocyte ratio) were documented. The probability of prostate cancer prediction in PI-RADS 3 lesions was calculated using 6 different machine-learning models, with the input parameters being the aforementioned variables. RESULTS: Of the 235 participants in the trial, 61 had malignant fusion biopsy pathology and 174 had benign pathology. Among 6 different machine learning algorithms, the random forest model had the highest accuracy (0.86±0.04; 95% CI 0.85-0.87), F1 score (0.91±0.03; 95% CI 0.91-0.92) and AUC value (0.92±0.06; 95% CI 0.88-0.90). In SHAP analysis based on random forest model, tumour ADC, tumour ADC/contralateral ADC ratio and PSA density were the 3 most successful parameters in predicting malignancy. On the other hand, systemic inflammatory index and neutrophil lymphocyte ratio showed higher accuracy in predicting malignancy than total PSA, age, free PSA/total PSA and lesion size in SHAP analysis. CONCLUSION: Among the machine learning models we developed, especially the random forest model can predict malignancy in PI-RADS 3 lesions and prevent unnecessary biopsy. This model can be used in clinical practice with multicentre studies including more patients.

Investigation of Transcription Factor and Cytokine Gene Expression Levels in Helper T Cell Subsets Among Turkish Patients Diagnosed with ICF2 (Novel ZBTB24 gene Variant) and ICF3 (CDCA7 Variant) Syndrome.

Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF), is a rare disease with autosomal recessive inheritance. ICF syndrome. It has been reported that ICF syndrome is caused by mutations in the DNMT3B (ICF1), ZBTB24 (ICF2), CDCA7 (ICF3), and HELLS (ICF4) genes. As a result of literature research, there are no studies on transcription factor and cytokine expressions of helper T cell subsets in ICF syndrome. In the study; Th1 (TBET, STAT1, STAT4), Th2 (GATA3, STAT6), Th17 (RORgt, STAT3), Treg (FoxP3, STAT5) transcription factors and the major cytokines of these cells (Th1; IFNG, Th2; IL4, Th17; IL17A-21-22, Treg; IL10, TGFß) expressions were aimed to be evaluated by qRT-PCR. Patients (ICF3: three patients; ICF2: two patients), six heterozygous individual and five healthy controls were included in the study. All patients had hypogammaglobulinemia. Except for the CD19 cells of P2 from patients diagnosed with ICF3, the CD3, CD4, CD8, and CD19 cells in the other ICF3 patients were normal. However, the rates of these cells were low in patients with ICF2 syndrome. Factors belonging to patients' Th1, Th17 and Treg cells were significantly lower than the control. Additionally, novel mutation was detected in ZBTB24 gene (c.1121-2 A > T). Our study is the first molecular study on Th cell subsets in patients with ICF syndrome and a new mutation that causes ICF2 syndrome has been identified.

Diverse Clinical and Immunological Profiles in Patients with IPEX Syndrome: a Multicenter Analysis from Turkey.

PURPOSE: Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic FOXP3 variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease. METHODS: Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cTFH) cells, and T-cell proliferation were analyzed. RESULTS: Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the TH2-like skewing accompanied by reduced TH17-like responses was observed in cTFH and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs. CONCLUSIONS: The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome.

Functional outcomes of organ sparing surgery for penile cancer confined to glans and premalignant lesions.

The first-line treatment of penile cancer confined to the glans (Tis-T2) is based on organ-sparing approaches. Our aim is to report functional outcomes of total glans resurfacing (TGR), wide local excision (WLE) and glansectomy. A retrospective analysis was conducted from January 2013 to October 2022. Ninety-nine patients were enrolled (22 TGR, 29 WLE, and 48 glansectomy). Sexual and urinary outcomes were explored using ad hoc and validated questionnaires (IIEF-15 and IPSS). The mean follow-up was 25.28 ± 24.87 months [95% CI: 20.38; 30.18]. 44 patients (12 TGR, 10 WLE, and 22 glansectomy) were assessed for functional outcomes. Overall, 86.36% of patients were satisfied with the surgery. The mean IIEF-15 score pre-operation was 54.91 ± 21.38 [95% CI: 48.41-61.41], and at 12 months post-operation, it was 44.39 ± 23.01 [95% CI: 37.39-51.39], with the change being statistically significant (mean difference: -10.52, (-19.15), p < 0.001). During the 0-12-month interval, IIEF-15 scores decreased across all techniques. Glansectomy and WLE showed significant decreases (Glansectomy: -12.955, -24.14%, [95% CI: -21.52, -4.38], p = 0.002; WLE: -14.1, -22.92%, [95% CI: -26.8, -1.39], p = 0.025 respectively), whereas TGR experienced a non-significant decrease (-3.083, -5.97%, CI: [-14.68, 8.51], p = 1.0). Concerning urinary function, only 18.18% of overall patients reported a negative impact of surgery. At 12-months, patients returned almost to pre-intervention IPSS values. Organ-sparing surgery guarantees a decent preservation of both erectile and voiding functions. TGR seems to provide better sexual outcomes when compared to other organ sparing approaches.

Surgical Treatment Results of Adult Tethered Spinal Cord Syndrome.

AIM: To present symptoms and surgical results of patients operated on with the diagnosis of tethered cord syndrome (TCS) in adulthood. MATERIAL AND METHODS: In this retrospective study, 20 patients older than 18 years were evaluated. There were 17 female and 3 male patients. Patient demographics, clinical and surgical results were evaluated. RESULTS: The mean age was 29.9 years and the mean follow-up period was 30 months. Of the 20 patients with low back and leg pain, 16 had relief. Two were partially benefited and 2 were unchanged. In nine patients, carrying heavy loads, excessive exercise, childbirth, and walking too long before the onset of symptoms were detected. Complaint of urinary incontinance was improved only in one patient. Three of them continued with frequent urination. There was no change in two of them. There was no improvement in sensory dysfunction and sphincter dysfunction. CONCLUSION: In patients diagnosed with TCS in adulthood, symptoms may begin with physical activity, and clinical recovery is better when early surgery is performed.

LUNGBANK: a novel biorepository strategy tailored for comprehensive multiomics analysis and P-medicine applications in lung cancer.

Background/aim: LUNGBANK was established as part of Project LUNGMARK, pioneering a biorepository dedicated exclusively to lung cancer research. It employs cutting-edge technologies to streamline the handling of biospecimens, ensuring the acquisition of high-quality samples. This infrastructure is fortified with robust data management capabilities, enabling seamless integration of diverse datasets. LUNGBANK functions not merely as a repository but as a sophisticated platform crucial for advancing lung cancer research, poised to facilitate significant discoveries. Materials and methods: LUNGBANK was meticulously designed to optimize every stage of biospecimen handling, from collection and storage to processing. Rigorous standard operating procedures and stringent quality control measures guarantee the integrity of collected biospecimens. Advanced data management protocols facilitate the efficient integration and analysis of various datasets, enhancing the depth and breadth of research possibilities in lung cancer. Results: LUNGBANK has amassed a comprehensive collection of biospecimens essential for unraveling the intricate molecular mechanisms of lung cancer. The integration of state-of-the-art technologies ensures the acquisition of top-tier data, fostering breakthroughs in translational and histological research. Moreover, the establishment of patient-derived systems by LUNGBANK underscores its pivotal role in personalized medicine approaches. Conclusion: The establishment of LUNGBANK marks a significant milestone in addressing the critical challenges of lung cancer research. By providing researchers with high-quality biospecimens and advanced research tools, LUNGBANK not only supports Project LUNGMARK's objectives but also contributes extensively to the broader landscape of personalized medicine. It promises to enhance our understanding of lung cancer initiation, progression, and therapeutic interventions tailored to individual patient needs, thereby advancing the field towards more effective diagnostic and therapeutic strategies.

Whey protein-loaded 3D-printed poly (lactic) acid scaffolds for wound dressing applications.

Chronic skin wounds pose a global clinical challenge, necessitating effective treatment strategies. This study explores the potential of 3D printed Poly Lactic Acid (PLA) scaffolds, enhanced with Whey Protein Concentrate (WPC) at varying concentrations (25, 35, and 50% wt), for wound healing applications. PLA's biocompatibility, biodegradability, and thermal stability make it an ideal material for medical applications. The addition of WPC aims to mimic the skin's extracellular matrix and enhance the bioactivity of the PLA scaffolds. Fourier Transform Infrared Spectroscopy results confirmed the successful loading of WPC into the 3D printed PLA-based scaffolds. Scanning Electron Microscopy (SEM) images revealed no significant differences in pore size between PLA/WPC scaffolds and pure PLA scaffolds. Mechanical strength tests showed similar tensile strength between pure PLA and PLA with 50% WPC scaffolds. However, scaffolds with lower WPC concentrations displayed reduced tensile strength. Notably, all PLA/WPC scaffolds exhibited increased strain at break compared to pure PLA. Swelling capacity was highest in PLA with 25% WPC, approximately 130% higher than pure PLA. Scaffolds with higher WPC concentrations also showed increased swelling and degradation rates. Drug release was found to be prolonged with increasing WPC concentration. After seven days of incubation, cell viability significantly increased in PLA with 50% WPC scaffolds compared to pure PLA scaffolds. This innovative approach could pave the way for personalized wound care strategies, offering tailored treatments and targeted drug delivery. However, further studies are needed to optimize the properties of these scaffolds and validate their effectiveness in clinical settings.

Extended Interportal Capsulotomy for Hip Arthroscopy, a Single-Center Clinical Experience.

Background and Objectives: The number of hip arthroscopy procedures is on the rise worldwide, and awareness regarding proper management of the hip capsule has increased. No capsulotomy shape is agreed upon as a standard approach, with literature supporting both isolated interportal and T-shaped capsulotomies. The aim of this retrospective cohort study is to report the clinical results of a standardized extended interportal capsulotomy (EIPC) during hip arthroscopy. Materials and Methods: Patients operated on between 2017 and 2020 with a hip arthroscopy were eligible. The inclusion criteria were ages 18-60 years, failed non-operative treatment, and at least a 2-year follow-up. Exclusion criteria were bilateral femoroacetabular impingement syndrome (FAS) cases or labral lesions, ipsilateral knee injury, history of ipsilateral hip surgery, and significant spine lesions. Data regarding demographic characteristics such as age, gender, operation date, BMI, but also Beighton score, presence of postoperative pudendal nerve damage, and revision for any reason were gathered from patients' records. All patients were evaluated preoperatively with a visual analog scale (VAS), the Hip Disability and Osteoarthritis Outcome Score (HOOS), and the modified Harris Hip Score (mHHS). Results: Of the 97 patients operated on with a hip arthroscopy between the defined dates, only 90 patients were included. The mean age was 37.9 ± 9.8, and 58.9% of patients were male. The most frequent surgical indication was an isolated FAS lesion (73.3%), followed by FAS associated with a labral tear (12.2%), an isolated labrum tear (10.0%), synovitis (3.3%), and a loose body (1.1%). The mean follow-up for the study cohort was 39.3 months. The majority of the patients had uneventful surgeries (76.7%), while there were three cases of sciatic nerve neuropraxia and 12 cases of pudendal nerve neuropraxia. Two patients underwent revision surgery during the study period. Comparison between preoperative and postoperative clinical scores showed a significant improvement with a final mHHS mean value of 67.7 ± 18.2, an HOOS value of 74.1 ± 13.2, and a low VAS score of 1.3 ± 1.2. Conclusions: A hip arthroscopy procedure with a standardized and unrepaired, extended interportal capsulotomy is a safe procedure with satisfactory mid-term results and high overall patient satisfaction. At a minimum of 2 years and a mean of 39.2 months, patients showed improved clinical scores and a low revision rate.

Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries.

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Machine learning algorithm predicts urethral stricture following transurethral prostate resection.

PURPOSE: To predict the post transurethral prostate resection(TURP) urethral stricture probability by applying different machine learning algorithms using the data obtained from preoperative blood parameters. METHODS: A retrospective analysis of data from patients who underwent bipolar-TURP encompassing patient characteristics, preoperative routine blood test outcomes, and post-surgery uroflowmetry were used to develop and educate machine learning models. Various metrics, such as F1 score, model accuracy, negative predictive value, positive predictive value, sensitivity, specificity, Youden Index, ROC AUC value, and confidence interval for each model, were used to assess the predictive performance of machine learning models for urethral stricture development. RESULTS: A total of 109 patients' data (55 patients without urethral stricture and 54 patients with urethral stricture) were included in the study after implementing strict inclusion and exclusion criteria. The preoperative Platelet Distribution Width, Mean Platelet Volume, Plateletcrit, Activated Partial Thromboplastin Time, and Prothrombin Time values were statistically meaningful between the two cohorts. After applying the data to the machine learning systems, the accuracy prediction scores for the diverse algorithms were as follows: decision trees (0.82), logistic regression (0.82), random forests (0.91), support vector machines (0.86), K-nearest neighbors (0.82), and naïve Bayes (0.77). CONCLUSION: Our machine learning models' accuracy in predicting the post-TURP urethral stricture probability has demonstrated significant success. Exploring prospective studies that integrate supplementary variables has the potential to enhance the precision and accuracy of machine learning models, consequently progressing their ability to predict post-TURP urethral stricture risk.

Impact of HLA-B51 on Uveitis and Retinal Vasculitis: Data from the AIDA International Network Registries on Ocular Inflammatory Disorders.

PURPOSE: The clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet's disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown. METHODS: Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time. RESULTS: Records of 213 patients (341 eyes) were analyzed. No differences in complications were observed (p = 0.465). With regard to VA, a significant difference was detected in median BCVA (p = 0.046), which was not maintained after Bonferroni correction (p = 0.060). RV was significantly more prevalent in NIU-affected patients who tested positive for HLA-B51, irrespective of the systemic diagnosis of BD (p = 0.025). No differences emerged in the occurrence of macular edema (p = 0.99). CONCLUSIONS: Patients with NIU testing positive for HLA-B51 exhibit an increased likelihood of RV throughout disease course, irrespective of a systemic diagnosis of BD. The rate of complications as well as VA are comparable between NIU cases unrelated to BD testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is advisable to perform the HLA-B typing in patients with NIU or retinal vasculitis, even in the absence of typical BD features.

A new strategy for the treatment of middle ear infection using ciprofloxacin/amoxicillin-loaded ethyl cellulose/polyhydroxybutyrate nanofibers.

A middle ear infection occurs due to the presence of several microorganisms behind the eardrum (tympanic membrane) and is very challenging to treat due to its unique location and requires a well-designed treatment. If not treated properly, the infection can result in severe symptoms and unavoidable side effects. In this study, excellent biocompatible ethyl cellulose (EC) and biodegradable polyhydroxybutyrate (PHB) biopolymer were used to fabricate drug-loaded nanofiber scaffolds using an electrospinning technique to overcome antibiotic overdose and insufficient efficacy of drug release during treatment. PHB polymer was produced from Halomonas sp., and the purity of PHB was found to around be 90 %. Additionally, ciprofloxacin (CIP) and amoxicillin (AMX) are highly preferable since both drugs are highly effective against gram-negative and gram-positive bacteria to treat several infections. Obtained smooth nanofibers were between 116.24 and 171.82 nm in diameter and the addition of PHB polymer and antibiotics improved the morphology of the nanofiber scaffolds. Thermal properties of the nanofiber scaffolds were tested and the highest Tg temperature resulted at 229 °C. The mechanical properties of the scaffolds were tested, and the highest tensile strength resulted in 4.65 ± 6.33 MPa. Also, drug-loaded scaffolds were treated against the most common microorganisms that cause the infection, such as S.aureus, E.coli, and P.aeruginosa, and resulted in inhibition zones between 10 and 21 mm. MTT assay was performed by culturing human adipose-derived mesenchymal stem cells (hAD MSCs) on the scaffolds. The morphology of the hAD MSCs' attachment was tested with SEM analysis and hAD MSCs were able to attach, spread, and live on each scaffold even on the day of 7. The cumulative drug release kinetics of CIP and AMX from drug-loaded scaffolds were analysed in phosphate-buffered saline (pH: 7.4) within different time intervals of up to 14 days using a UV spectrophotometer. Furthermore, the drug release showed that the First-Order and Korsmeyer-Peppas models were the most suitable kinetic models. Animal testing was performed on SD rats, matrix and collagen deposition occurred on days 5 and 10, which were observed using Hematoxylin-eosin and Masson's trichrome staining. At the highest drug concentration, a better repair effect was observed. Results were promising and showed potential for novel treatment.

Three-Dimensional-Printed GelMA-KerMA Composite Patches as an Innovative Platform for Potential Tissue Engineering of Tympanic Membrane Perforations.

Tympanic membrane (TM) perforations, primarily induced by middle ear infections, the introduction of foreign objects into the ear, and acoustic trauma, lead to hearing abnormalities and ear infections. We describe the design and fabrication of a novel composite patch containing photocrosslinkable gelatin methacryloyl (GelMA) and keratin methacryloyl (KerMA) hydrogels. GelMA-KerMA patches containing conical microneedles in their design were developed using the digital light processing (DLP) 3D printing approach. Following this, the patches were biofunctionalized by applying a coaxial coating with PVA nanoparticles loaded with gentamicin (GEN) and fibroblast growth factor (FGF-2) with the Electrohydrodynamic Atomization (EHDA) method. The developed nanoparticle-coated 3D-printed patches were evaluated in terms of their chemical, morphological, mechanical, swelling, and degradation behavior. In addition, the GEN and FGF-2 release profiles, antimicrobial properties, and biocompatibility of the patches were examined in vitro. The morphological assessment verified the successful fabrication and nanoparticle coating of the 3D-printed GelMA-KerMA patches. The outcomes of antibacterial tests demonstrated that GEN@PVA/GelMA-KerMA patches exhibited substantial antibacterial efficacy against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Furthermore, cell culture studies revealed that GelMA-KerMA patches were biocompatible with human adipose-derived mesenchymal stem cells (hADMSC) and supported cell attachment and proliferation without any cytotoxicity. These findings indicated that biofunctional 3D-printed GelMA-KerMA patches have the potential to be a promising therapeutic approach for addressing TM perforations.

Single-Walled (Magnetic) Carbon Nanotubes in a Pectin Matrix in the Design of an Allantoin Delivery System.

Single-walled carbon nanotubes (SWCNTs) outperform other materials due to their high conductivity, large specific surface area, and chemical resistance. They have numerous biomedical applications, including the magnetization of the SWCNT (mSWCNT). The drug loading and release properties of see-through pectin hydrogels doped with SWCNTs and mSWCNTs were evaluated in this study. The active molecule in the hydrogel structure is allantoin, and calcium chloride serves as a cross-linker. In addition to mixing, absorption, and swelling techniques, drug loading into carbon nanotubes was also been studied. To characterize the films, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), Fourier transform infrared (FTIR) spectroscopy, surface contact angle measurements, and opacity analysis were carried out. Apart from these, a rheological analysis was also carried out to examine the flow properties of the hydrogels. The study was also expanded to include N-(9-fluorenyl methoxycarbonyl)glycine-coated SWCNTs and mSWCNTs as additives to evaluate the efficiency of the drug-loading approach. Although the CNT additive was used at a 1:1000 weight ratio, it had a significant impact on the hydrogel properties. This effect, which was first observed in the thermal properties, was confirmed in rheological analyses by increasing solution viscosity. Additionally, rheological analysis and drug release profiles show that the type of additive causes a change in the matrix structure. According to TGA findings, even though SWCNTs and mSWCNTs were not coated more than 5%, the coating had a significant effect on drug release control. In addition to all findings, cell viability tests revealed that hydrogels with various additives could be used for visual wound monitoring, hyperthermia treatment, and allantoin release in wound treatment applications.

Unveiling the molecular Hallmarks of Peyronie's disease: a comprehensive narrative review.

Peyronie's disease, a fibroinflammatory disorder, detrimentally impacts the sexual well-being of men and their partners. The manifestation of fibrotic plaques within penile tissue, attributed to dysregulated fibrogenesis, is pathognomonic for this condition. The onset of fibrosis hinges on the perturbation of the equilibrium between matrix metalloproteinases (MMPs), crucial enzymes governing the extracellular matrix, and tissue inhibitors of MMPs (TIMPs). In the context of Peyronie's disease, there is an elevation in TIMP levels coupled with a decline in MMP levels, culminating in fibrogenesis. Despite the scant molecular insights into fibrotic pathologies, particularly in the context of Peyronie's disease, a comprehensive literature search spanning 1995 to 2023, utilizing PubMed Library, was conducted to elucidate these mechanisms. The findings underscore the involvement of growth factors such as FGF and PDGF, and cytokines like IL-1 and IL-6, alongside PAI-1, PTX-3, HIF, and IgG4 in the fibrotic cascade. Given the tissue-specific modulation of fibrosis, comprehending the molecular underpinnings of penile fibrosis becomes imperative for the innovation of novel and efficacious therapies targeting Peyronie's disease. This review stands as a valuable resource for researchers and clinicians engaged in investigating the molecular basis of fibrotic diseases, offering guidance for advancements in understanding Peyronie's disease.