Abstract: Objectives: Finding correlations between vitamin D deficiency and thyroid autoimmune pathology in a group of patients from Dobrogea, the non-endemic geographical area, with a high degree of sunshine.An important factor in maintaining immunological balance is represented by an adequate level of vitamin D, multiple studies suggesting that vitamin D deficiency is associated with a higher incidence of autoimmune diseases. Recent studies analyze the possible effect of this factor in promoting autoimmunity, the serum level of BAFF being often increased among patients with systemic autoimmune diseases. Methods : The study included 80 patients with autoimmune thyroid pathology, from Dobrogea area. The entire study group (n = 80) was divided according to the established diagnosis into two study groups: Group 1 – including 62 patients with CAT and Group 2 – including 18 patients with GD. Results: Vitamin D study average values of 25-OH-vitamin D found statistically significant differences between vitamin D values in the two groups (p = 0.018). Determination of BAFF serum levels among patients with CAT and GD obtained a lower mean value of BAFF for the CAT group compared to GD group. The evolution of BAFF serum level related to the serum levels of the antithyroid antibodies ATPO and ATG was also analyzed. For patients with GD, BAFF was not correlated with the value of ATPO or ATG, but in the patients with CAT, a correlation was found between the value of BAFF and the level of ATG but not with ATPO level. Conclusions: The study analyzed BAFF serum levels in patients with CAT and respectively GD as a result of that BAFF acts as a stimulatory factor of immunoglobulin production in autoimmune diseases. These results require clarifying the role and therapeutic benefits of supplementing vitamin D intake in patients with autoimmune diseases.

Abstract: Hypertension disorders of pregnancy affect almost 10% of pregnancies. Most hypertensive disorders associated with pregnancy, including chronic hypertension and gestational hypertension, often persist into the postpartum period. Thus, many breastfeeding mothers require ongoing antihypertensive treatment with antihypertensive medications while nursing. This highlights the importance of understanding the efficacy, safety, and potential adverse effects of antihypertensive therapy in breastfeeding mothers. Unfortunately, research in this area is limited, and references in clinical guidelines remain sparse. Our review aims to provide a comprehensive summary of the current knowledge on antihypertensive medications during breastfeeding, drawing from available research and evidence-based guidelines. This article discusses all groups of antihypertensive drugs, presenting societies' recommendations and available clinical data. Based on the available literature, calcium channel blockers (nifedipine as the first choice) and diuretics and beta-blockers (labetalol, metoprolol, propranolol) appear to be the drugs of choice. Our review highlights the need for further research to evaluate the long-term safety of antihypertensive medications during breastfeeding, improve clinical guidelines, and ensure optimal treatment for nursing mothers.

Abstract: The aim of this study was to investigate the effect of base material, restorative material and finish line on marginal and internal fit and fracture strength (FS) of endocrowns (N = 64). The restorative materials were ceramic and hybrid ceramic, the preparations were ferrule and modified butt joint (BJ) with two grooves, and the bases were with and without fiber ribbon. Marginal and internal fit were assessed using the triple scan. Statistical analyses were performed using three-way ANOVA. The absolute marginal discrepancy (AMD), marginal discrepancy and overall fit values obtained for ceramic were 127 µm, 108 µm and 120 µm, whereas those obtained for hybrid ceramic were 139 µm, 116 µm and 130 µm, respectively (p < 0.05). The overall FS obtained for ceramic was 662 N, whereas that for hybrid ceramic was 903 N (p < 0.001). When the material was evaluated regardless of preparation and base, ceramic and hybrid ceramic exceeded the selected clinical acceptability threshold for AMD, but did not exceed it for other parameters. Hybrid ceramic restorations with ferrules and fiber bases tended to provide the highest FS, whereas ceramic restorations with modified BJs and without fiber bases tended to provide the lowest FS.

Abstract: Natural autoantibodies (nAAbs) recognize self-antigens and are an important component of the immune system have evolved from invertebrates to vertebrates and are viewed as stable by-products of immune function to essential players in health and disease. Initially characterized by their conserved nature and multi-reactivity, primarily as IgM isotypes, nAAbs are now recog-nized for their adaptability in response to infections and vaccinations, bridging innate and adaptive immunity. The nAAbs and the cellular elements, such as γδ-T, iNKT, and MAIT cells of the natural immune system, perform a primary defense network with moderate antigen-specificity. This comprehensive literature review was conducted to analyze the role of natural autoantibodies (nAAbs) in health and disease. The review focused on research published over the past 40 years, emphasizing studies related to infectious diseases, vaccinations, and autoimmune disorders. Recent studies suggest that nAAbs engage in complex interactions in autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and type 1 diabetes. Their roles in immunological processes, such as maternal tolerance during pregnancy, further underscore their complexity. Emerging evidence indicates that nAAbs and the cellular elements of the natural immune system may contribute to both disease pathogenesis and protective mechanisms, highlighting their dual nature. Continued research on nAAbs is vital for improving our understanding of immune responses and developing therapeutic strategies for autoimmune disorders and infectious diseases.

Abstract: Background. An inflammatory foreign-body reaction and the neosynthesis of collagen and the extracellular matrix through injectable collagen stimulators have coexisted since the introduction of the first sterile water-reconstituted poly-L-lactic acid (PLLA) formulation around the turn of the century. The PLLA-LASYNPRO™ microspheres for subdermal implants are a groundbreaking technological advancement that challenges the foreign-body reaction paradigm. The concept of non-inflammatory collagen and extracellular matrix regeneration, along with the initial insights into the rationale and role of the new-technology subdermal implants in aesthetic and regenerative medicine, was central to the discussions among thirteen distinguished experts in micro-invasive aesthetic medicine, aesthetic plastic surgery, and dermatology. This document summarizes their conclusions regarding the PLLA-LASYNPRO™ concept—subdermal microsphere implants designed to facilitate collagen and extracellular matrix regeneration while negligibly triggering persistent inflammation. Additionally, it offers preliminary yet authoritative suggestions from the board for the safe and effective use of the novel JULÄINE™ medical device based on the new-technology microspheres. Methods. An online survey of the experts, preceded by a board discussion in Milan, Italy, focused on skin regeneration and the rationale for the new PLLA technology, drawing on the board experts’ direct experience. The topics surveyed included the anticipated benefits of the new JULÄINE™ medical device and some initial suggestions for its safe and effective use. Results and Conclusions. This document outlines the board’s considerations regarding the shift, driven by the innovative PLLA-LASYNPRO™ ingredient and the CE-approved JULÄINE™ medical device, from the historically dominant FBR paradigm to a new strategy focusing on non-inflammatory collagen and extracellular matrix regeneration. Additionally, it presents practical, albeit preliminary, suggestions based on current clinical research for utilizing the new JULÄINE™ medical device and reaping its anticipated benefits.

Abstract: Integrating artificial intelligence (AI) and mixed reality (MR) into orthopedic education has transformed learning. This review examines AI-powered platforms like Microsoft HoloLens, Apple Vision Pro, and HTC Vive Pro, which enhance anatomical visualization, surgical simulation, and clinical decision-making. These technologies improve spatial understanding of musculoskeletal structures, refine procedural skills with haptic feedback, and personalize learning through AI-driven adaptive algorithms. Generative AI tools like ChatGPT further support knowledge retention and provide evidence-based insights on orthopedic topics. AI-enabled platforms and generative AI tools help address challenges in standardizing orthopedic education. However, we still face many barriers that relate to standardizing data, algorithm evaluation, ethics, and the curriculum. AI is used in preoperative planning and predictive analytics in the postoperative period that bridges theory and practice. AI and MR are key to supporting innovation and scalability in orthopedic education. However, technological innovation relies on collaborative partnerships to develop equitable, evidence-informed practices that can be implemented in orthopedic education. For sustained impact, innovation must be aligned with pedagogical theories and principles. We believe that orthopedic medical educator's future critical role will be to enhance the next generation of competent clinicians.

Abstract: Rapid, safe, and field-deployable molecular diagnostics are crucial for effective man-agement of infectious disease outbreaks, particularly those involving highly infectious pathogens, which can produce clinical symptoms similar to less infectious pathogens, thus raising potential biosafety concerns. In this study, we evaluated DNA/RNA De-fend Pro (DRDP) buffer, a novel viral-inactivating transport medium designed to stabilize nucleic acids and allow direct PCR without nucleic acid extraction. To ensure critical qPCR parameters were not compromised by using DRDP, we conducted serial dilution tests using herpes simplex viruses 1 and 2 (HSV-1, HSV-2) and varicel-la-zoster virus (VZV), comparing DRDP to standard universal transport medium (UTM). Detection sensitivity, determined by cycle quantification (Cq) values, slightly favored DRDP, as UTM samples required a 2–3-fold dilution to mitigate PCR inhibition. DRDP maintained reliable PCR compatibility at reaction volumes containing up to 25% buffer. At higher DRDP concentrations (30–35%), PCR inhibition occurred due to EDTA content but was fully reversible by adding supplemental magnesium. Fur-thermore, DRDP samples did not require an initial 95 °C thermal lysis step, thus simplifying the procedure without reducing PCR sensitivity or efficiency.

Abstract: Background/Objectives. Flavonoids are a vast class of phenolic substances. To date, approximately 6000 plant-origin flavonoids have been discovered, and many of them have been used in drug therapy. Therapeutic flavonoids are commonly formulated to conventional “one size fits all” dosage forms, such as conventional tablets or hard cap-sules. However, the current trend in pharmacy and medicine is personalized drug therapy and drug delivery systems (DDSs). Therefore, 3D printing is an interesting technique for designing and preparing novel personalized pharmaceuticals for flavo-noids. The aim of the present study was to develop aqueous polyethylene oxide (PEO) gel inks loaded with plant-origin rutin (vitamin P) for semisolid-extrusion (SSE) 3D printing. Methods. Rutin (a model substance for therapeutic flavonoids), Tween 80, PEO (MW approx. 900,000), ethanol, and purified water were used in PEO gels at different pro-portions. The viscosity and homogeneity of the gels were determined. The rutin-PEO gels were printed with a bench-top Hyrel 3D printer to lattices and discs, and their weight and effective surface area were investigated. Results. The key SSE 3D printing process pa-rameters were established and verified. The results showed the compatibility of rutin as a model flavonoid and PEO as a carrier polymer. The rutin content (%) and content uniformity of the 3D-printed preparations were assayed by UV spectrophotometry and high-performance liquid chromatography (HPLC). Conclusions. The most feasible aqueous PEO gel ink formulation for SSE 3D printing contained rutin 100 mg/ml and Tween 80 50 mg/ml in a 12% aqueous PEO gel. The 3D-printed dosage forms are intended for the oral administration of flavonoids.

Abstract: Background/Objectives: Inflammatory bowel diseases (IBD) include Crohn’s disease (CD) and ulcerative colitis (UC). The availability of an increasing number of new mol-ecules approved for IBD treatment has increased our ability and aspirations to change their natural history. The STRIDE II consensus is the current established suggested strategy for IBD management. Primary objective of this study is to describe the clinical history of IBD in post-STRIDE era, and to quantify the burden of IBD in terms of hos-pitalization rate. Secondary objective is to estimate the 5-years risk of intestinal resec-tion among IBD patiesnts. Methods: Observational time series analysis was conducted on population data; retrospective data from Jan 2011 was collected for Local Health Authority “Roma 1” population (circa 1.5 million residents). Prospective data from hospitalizations among residents since Jan 2018 was also collected. Hospitalization and surgery events among newly diagnosed patients (n= 556) were collected and pro-spectively followed since Jan 2018. Kaplan-Mayer survivor functions were proposed, considering surgical intervention as primary outcome. Results: Current IBD preva-lence is estimated to be 218 (77.2 CD, 141.1 UC) cases/100,000ppl. Incidence trend slowly increased during the last decade up to 5.3 (CD) and 9.4 (UC) cas-es/100,000ppl/year. Yearly hospitalization remained constant near 16.5%, while 6-years risk of surgery is 36% for CD, and 20% for UC. Conclusions: Incidence of IBD increased in the last decades, with substantial stability in the incidence of surgeries and hospitalizations. Thus, current IBD management has only a small effect on changing the natural history of the disease.

Abstract: Electroconvulsive therapy (ECT) remains one of the most effective interventions for treatment-resistant psychiatric disorders, particularly major depressive disorder and bipolar disorder. Despite extensive clinical and preclinical investigations the precise neurobiological mechanisms underlying ECT’s therapeutic effects are not fully understood. This review explores the molecular and cellular pathways involved in ECT, emphasizing its impact on neurotrophic signaling, oxidative stress, apoptosis, and neuroplasticity. Evidence suggests that ECT modulates brain-derived neurotrophic factor (BDNF) and other neurotrophic factors, promoting synaptic plasticity and neuronal survival. Additionally, ECT influences the hypothalamic-pituitary-adrenal (HPA) axis, reduces neuroinflammation, and alters neurotransmitter systems, contributing to its antidepressant effects. Recent findings also highlight the role of mitochondrial function and oxidative stress regulation in ECT-induced neural adaptation. By synthesizing current molecular insights, this review provides a comprehensive perspective on the neurobiological mechanisms of ECT, offering potential directions for future research and therapeutic advancements in brain stimulation.

Abstract: How injectable collagen stimulators promote the neosynthesis of collagen and other components of the extracellular matrix in connective tissues has typically been linked to an inflammatory foreign-body reaction (FBR). A shift from the long-dominant inflammatory FBR paradigm to a new focus on non-inflammatory collagen and extracellular matrix regeneration may have emerged with the next-generation PLLA-LASYNPRO™ microspheres of the CE-approved JULÄINE™ medical device, which preclinical studies suggest are negligibly likely to trigger inflammation. A survey and subsequent discussions during a board meeting held in Milan, Italy, which involved thirteen distinguished experts in micro-invasive aesthetic medicine, aesthetic plastic surgery, and dermatology, led to this document and the accompanying manuscript “First Insights on the Upcoming Role of Next-Generation PLLA-LASYNPRO™ in Aesthetic and Regenerative Medicine. A Survey of Experts — Practical Suggestions”. This first paper outlines the initial insights and discussion of the experts on the basis and the value of the non-inflammatory rationale proposed for PLLA-LASYNPRO™ subdermal implants in aesthetic and regenerative medicine.

Abstract: Background/Objectives: Primary Ciliary Dyskinesia (PCD) is a rare genetic condition characterized by compromised mucociliary clearance and chronic respiratory manifestations. Anosmia, or the loss of smell, is a lesser-known but clinically relevant symptom that can significantly impact patient safety, nutritional status, and overall quality of life. The RSPH4A (c.921+3_921+6delAAGT) founder mutation is highly prevalent among Puerto Rican individuals with PCD and may carry distinct phenotypic implications. This study aimed to evaluate olfactory function in Puerto Rican PCD patients with this mutation using the Brief Smell Identification Test (BSIT) and to assess associations with age and sex. Methods: We conducted a case-control study involving 30 participants: 15 PCD patients with genetically confirmed RSPH4A mutations and 15 age- and sex-matched healthy controls. All participants completed the BSIT, and BSIT scores were compared by diagnosis, sex, and age. Results: PCD patients had significantly lower BSIT scores than controls (p = 0.0015). When stratified by sex, both male (p = 0.0289) and female (p = 0.0178) PCD patients demonstrated significantly lower BSIT scores compared to their respective healthy counterparts. Regression analysis showed a significant inverse correlation between age and BSIT score in the PCD group (r² = 0.2873, p = 0.0395), while no such relationship was observed in controls (r² = 0.0096, p = 0.7283). Among PCD patients, age-related decline in olfactory function was more pronounced in females (r² = 0.71, p = 0.005) than in males (r² = 0.31, p = 0.25). Conclusions: These findings demonstrate that the RSPH4A founder mutation is associated with measurable olfactory impairment in PCD patients, particularly in females and with advancing age. Routine assessment of olfactory function should be considered in the clinical evaluation of patients with PCD, as anosmia may represent a key phenotypic feature and contribute to disease burden.

Abstract: Background/objectives: Gluten-free diets have become very popular in recent years and unjustified exclusion of gluten happens extremely frequently. There are isolated reports which warn that symptoms of psoriasis, atopic dermatitis or chronic urticaria can be aggravated by the supply of gluten in the patient's diet. The aim of the study was (i) to assess the prevalence of antibodies typical for gluten-dependent enteropathy in patients with the above-mentioned skin diseases and in the comparison group; (ii) to assess the relationship between the declared diet in patients with selected dermatoses and the presence of antibodies typical for gluten-dependent enteropathy; (iii) to assess the occurrence of IgE specific to selected allergens, including wheat and rye flours, in the studied groups; (iv) to assess dietary behaviour in patients with selected skin diseases and in the comparison group. Methods: An interviewer-supervised auditory questionnaire was used to obtain information on the health status of the subjects. Their individual gluten intake was assessed by means of one of the retrospective dietary assessment methods. The method of consumption frequency was applied. Antibodies directed against smooth muscle endomysium, tissue transglutaminase and gliadin were detected in the patients and in the comparison group. The tests were performed using ready-made kits according to the manufacturer's recommended test instructions. In addition, blood allergy tests were performed in all the subjects in the study and control groups. Results: Based on the study, the diagnosis of visceral disease and gluten allergy was ruled out in all the subjects. However, significant differences were shown regarding the intake of certain foods. Conclusions: In patients with autoimmune diseases with associated gastrointestinal symptoms, a full diagnostic workup for gluten-dependent enteropathy and gluten intolerance is necessary. Patients who report gastrointestinal symptoms should not implement a gluten-free diet without appropriate diagnostics and consultation with their doctor.

Abstract: Background/Objectives: Fast-track (FT) protocols have been developed to reduce the surgical burden and enhance recovery, but they still need to be established for carotid endarterectomy (CEA). In this scenario, carotid stenting has gained momentum by answering the need for a less invasive treatment, despite a still debated clinical advantage. We aim to propose a FT protocol for CEA, along with the analysis of its clinical impact. Methods: This retrospective, monocentric study enrolled consecutive patients who underwent CEA for asymptomatic carotid stenosis using a FT protocol between January 2016 and December 2024. Patients undergoing CEA for symptomatic carotid stenosis, carotid bypass procedures, and combined interventions were excluded. Our FT protocol comprises same-day hospital admission, exclusive use of local anesthesia, non-invasive assessment of cardiac and neurological status, and selective utilization of cervical drainage. Discharge criteria were goal-directed and included the absence of pain, electrocardiographic abnormalities, hemodynamic instability, neck hematoma, or cranial nerve injury, with a structured plan for rapid readmission if required.Postoperative pain was assessed using the Numerical Rating Scale (NRS), administered to all patients. The perioperative clinical impact of the protocol was evaluated based on complication rates, pain control, length of hospital stay, and early readmission rates. Results: Among 1051 patients who underwent CEA, 853 met the inclusion criteria. General anesthesia was required in 17 cases (2%), while a cervical drain was placed in 83 patients (10%). The eversion technique was employed in 765 cases (90%). Postoperative intensive care unit (ICU) monitoring was necessary for 7 patients (1%). The mean length of hospital stay was 1.17 days.Postoperatively, 17 patients (2%) required surgical revision. Minor stroke occurred in 3 patients (0.4%), and acute myocardial infarction requiring angioplasty in 2 patients (0.2%). Inadequate postoperative pain control (NRS >4) was reported by 5 patients (0.6%). Hospital readmission was required for one patient due to a neck hematoma. Conclusions: Our fast-track protocol for elective carotid surgery, designed to mitigate operative stress, demonstrated effectiveness in optimizing the quality of care, yielding significantly favorable outcomes in patients' clinical courses.

Abstract: Introduction. Paediatric intensive care units (PICUs) provide special and comprehensive care and treatment to critically ill children. These factors lead to the exposure of the personnel to stress and the risk of developing burnout syndrome. Methods and participants. In order to evaluate burnout syndrome among physicians employed at PICUs, we carried out our study between September and December of 2023. With the authors' consent, we used a survey that was published in June 2023 in Acta Paediatrica (https://onlinelibrary.wiley.com). The survey was distributed to the physicians working in the existing PICUs in Bulgaria after being translated and reviewed. Results. A total of 37/43 (83.7%) doctors and two clinical psychologists completed the survey. More women than men took part in the study. Of the respondents, 36% were paediatricians, and 30% were specialists in Anesthesiology and Intensive care. In total, 70.3% of the staff reported working between 40-50 hours/week, and 24.3% working more than 50 hours/week; 73% of the employees experienced an episode of overheating, depression, and anxiety. Of all, 75.6% felt exhausted from work, and 43.2% defined themselves as "crushed”. Despite the difficulties that the staff faced, the majority of the doctors express satisfaction with their work and would choose the same specialty again. Conclusion. This study presents for the first time quantitative data on Bulgarian physicians' burnout in PICUs. Burnout among healthcare professionals is a worldwide issue that has a detrimental effect on staff productivity, patient care quality, and hiring medical personnel. Specific solutions are required, such as the establishment of paediatric intensive care as a distinct specialty.

Abstract: Background. It has yet to be determined whether the immunocytological profile of the bronchoalveolar lavage (BAL) in respiratory post-COVID syndrome (PCS) may reflect the risk of persistent interstitial lung disease (ILD), including pulmonary fibrosis. We aimed to assess the prognostic value of BAL cytoimmunologic profile in PCS-related ILD. Material & Methods. We enrolled 58 non-smoking patients with COVID-19 history, having new-onset ILD, divided into PCS remission and PCS persistence groups, based on clinical data including repeated computed tomography and pulmonary function tests. We phenotyped BAL major T cell subsets, immune checkpoints (including programmed cell death-1, PD1) and markers of Th1/Th2/Th17 polarization. Results. PCS compared to controls showed increased total cell, lymphocyte and neutrophil count and high BAL neutrophil:lymphocyte ratio (NLR). PCS persistence compared to controls presented increased neutrophil count (26[17-36] vs. 2.6[1.9-5.4] 10³/ml, median[Q1-Q3], p<0.001) and percentage, BAL NLR (0.77[0.26-1.63] vs. 0.21[0.17-0.31], p<0.0001), CD8+PD1+ cell percentage (43.5 [34-60.5] vs. 24.5[22-44]%, p=0.045), decreased CD4:CD8 ratio. High percentage of CD4+CD196+CD183- cells (relevant to Th17 activity, 6.2[2.0-9.4] vs 1.2[0.7-2.7]%, p=0.02), and increased BAL supernatant elevated IL-8 levels (62.5[16-243] vs. 10.9[3.44-32]pg/mL, p=0.002) were found in PCS persistence vs. controls. In total PCS, predicted values of Vital Capacity (VC) and Diffusing Lung Capacity for CO (DLCO) correlated negatively with BAL NLR, VC correlated negatively with BAL CD8+PD1+; DLCO correlated positively with CD4:CD8 ratio. Conslusions. Worse prognosis in PCS is associated with higher BAL NLR, BAL neutrophilia, elevated percentage of CD8+PD1+ lymphocytes, decline in CD4:CD8 ratio. Th17 cells and IL-8 participate in lung PCS persistence.

Abstract: Complex ventral hernia repairs pose unique challenges in high-risk patients with impaired tissue quality or contaminated fields. While traditional synthetic meshes are effective, their use in these scenarios carries an increased risk of chronic inflammation and infection. Biologic and bioabsorbable meshes are alternative options designed to provide a temporary scaffolding that supports tissue healing while minimizing foreign body reactions. This paper explores the strengths and limitations of biologic, bioabsorbable, and hybrid meshes, particularly in contaminated or high-risk settings. Biologic meshes, though costly, offer temporary reinforcement and promote tissue integration, while absorbable meshes present a viable alternative with promising safety data. Hybrid meshes, which combine durability with biocompatibility, represent a promising class of materials, particularly for patients with impaired wound healing. As the field advances, further research and comparative studies will be critical to optimizing mesh selection and improving long-term outcomes in complex ventral hernia repair.

Abstract: Background/Objectives: Aminoglycosides (AG) have been extensively used to treat bacterial diseases for decades. Nevertheless, despite their effectiveness, several secondary adverse effects (auditory, renal, and neurological) have been evident. Although the mechanisms of these side effects of AG are still unclear, there is a consensus that megalin is a drug receptor that participates in AG endocytosis. We aimed to explore the interaction between megalin and AGs to explain their ototoxicity side effect by combining in silico studies and cell functionality assays. Methods: Molecular dynamics simulations on the 10^th CR domain of human megalin were performed using GROMACS. Seven commonly prescribed AG were docked against the surface of three conformations of this domain megalin derived from the simulations' trajectories. Gentamicin, the AG with the strongest affinity, was selected for cell functionality evaluation using HEK293 cells and Resazurin assays. Results: Docking results revealed that aspartic acids play a crucial role in the binding affinity to AGs, forming key electrostatic interactions. The models of the Megalin-AG complexes allowed the determination of electrostatic and non-electrostatic contributions to the free energy change of binding (ΔG_b). Gentamicin, Tobramycin, and Neomycin showed a higher affinity for megalin than Kanamycin, Hygromycin, Paromomycin, and Streptomycin. Cell functionality of HEK293 cells was reduced by Gentamicin. Conclusion: the 10^th CR domain of Megalin plays a critical role in AG-induced ototoxicity through electrostatic interactions mainly involving aspartic acid residues. It binds with higher affinity to Gentamicin, Tobramycin, and Neomycin than Kanamycin, Hygromycin, Paromomycin, and Streptomycin. Furthermore, we observed the reduced functionality of HEK293 cells induced by gentamicin. These results highlight megalin as a potential therapeutic target to mitigate/alleviate the adverse side effects of aminoglycoside.

Abstract: Background: Endophthalmitis associated with intraocular procedures is an infection of the eye that can rapidly result in substantial irreversible loss of vision and may even lead to removal of the eye. Prevention strategies vary globally and often include antibiotic use – often consisting of a broad spectrum mono-therapeutic agent. The purpose of this study is to test the efficacy and value of combinations of cefuroxime (cefu), cefazolin (cefa), azithromycin (azith), and/or tobramycin (tob) as alternatives to the use of moxifloxacin. We looked for synergism since these antimicrobials used different mechanisms of inhibition.Methods: Initially, we examined individual antimicrobials to determine the minimal bactericidal concentrations (MBC) of each individual treatment, against Klebsiella pneumonia, Pseudomonas aeruginosa, Staphylococcus aureus, two clinical isolates of MRSA, and Staphylococcus epidermidis, by both the Zone of Inhibition (ZOI) and the Colony Forming Unit (CFU) assays. We then used this data in a combinatorial study. Results: We found combinations that were synergistic against all the bacteria tested, resulting in total killing of all bacteria. We found that the ZOI assay provided less consistent results than the CFU assays.Conclusions: We have found combinations of these antimicrobials that were synergistic in total killing (8 logs) of all bacteria tested. These three combinations were: cefu/azith; azith/tob; and cefu/tob. Moxifloxacin (Vigamox) did not completely kill Staphylococcus epidermidis

Abstract: Background/Objectives: Sacituzumab govitecan (SG) is an antibody-drug conjugate targeting Trop-2, approved for use in metastatic triple-negative breast cancer (mTNBC) and more recently in hormone receptor-positive/HER2-negative (mHRPBC) subtypes. While clinical trials have demonstrated its efficacy, real-world da-ta—especially involving both molecular subtypes—remain scarce. This multicenter, retrospective study aimed to evaluate the real-life effectiveness, safety, and prognostic factors associated with SG treatment in patients with both mTNBC and mHRPBC. Methods: A total of 68 patients treated with SG between 2022 and 2025 were included from multiple oncology centers in Turkey. Patients with mTNBC were required to have received at least one prior chemotherapy line, while mHRPBC patients had received at least two prior chemotherapy lines in addition to hormone therapy. Clinical out-comes—including progression-free survival (PFS), overall survival (OS), and objective response rate (ORR)—were evaluated. Univariate and multivariate analyses were performed to identify factors influencing outcomes. Adverse events (AEs) were also documented and graded according to NCI-CTCAE v5.0. Results: The cohort included 35 (51.5%) mTNBC and 33 (48.5%) mHRPBC patients. The median PFS was 6.1 months, and the median OS was 12.5 months, with no significant differences between subtypes. The ORR was 52.9%, with a complete response observed in 10.3% of patients. Eastern cooperative oncology group performance status (ECOG PS) and liver metastasis were independent predictors of poorer PFS and OS. Prior immunotherapy did not negatively impact SG efficacy. SG was generally well tolerated; the most common AEs were alo-pecia, anemia, neutropenia, and diarrhea. Treatment discontinuation due to AEs was rare (2.9%). Conclusions: SG demonstrated comparable effectiveness and a managea-ble safety profile in real-world patients with both mTNBC and mHRPBC. Importantly, this study provides one of the first real-world datasets evaluating SG in the mHRPBC subgroup, highlighting its potential role beyond clinical trials. These results support SG as a valuable therapeutic option in heavily pretreated patients, warranting further prospective and biomarker-driven studies.