Cardiovascular Risk Factors as Independent Predictors of Diabetic Retinopathy in Type II Diabetes Mellitus: The Development of a Predictive Model.

Background: Diabetic retinopathy (DR) is a leading cause of blindness in patients with type 2 diabetes mellitus (T2DM). Cardiovascular risk factors, such as hypertension, obesity, and dyslipidemia, may play a crucial role in the development and progression of DR, though the evidence remains mixed. This study aimed to assess cardiovascular risk factors as independent predictors of DR and to develop a predictive model for DR progression in T2DM patients. Methods: A retrospective cross-sectional study was conducted on 377 patients with T2DM who underwent a comprehensive eye exam. Clinical data, including blood pressure, lipid profile, BMI, and smoking status, were collected. DR staging was determined through fundus photography and classified as No DR, Non-Proliferative DR (NPDR), and Mild, Moderate, Severe, or Proliferative DR (PDR). A Multivariate Logistic Regression was used to evaluate the association between cardiovascular risk factors and DR presence. Several machine learning models, including Random Forest, XGBoost, and Support Vector Machines, were applied to assess the predictive value of cardiovascular risk factors and identify key predictors. Model performance was evaluated using accuracy, precision, recall, and ROC-AUC. Results: The prevalence of DR in the cohort was 41.6%, with 34.5% having NPDR and 7.1% having PDR. A multivariate analysis identified systolic blood pressure (SBP), LDL cholesterol, and body mass index (BMI) as independent predictors of DR progression (p < 0.05). The Random Forest model showed a moderate predictive ability, with an AUC of 0.62 for distinguishing between the presence and absence of DR XGBoost showing a better performance, featuring a ROC-AUC of 0.68, while SBP, HDL cholesterol, and BMI were consistently identified as the most important predictors across models. After tuning, the XGBoost model showed a notable improvement, with an ROC-AUC of 0.72. Conclusions: Cardiovascular risk factors, particularly BP and BMI, play a significant role in the progression of DR in patients with T2DM. The predictive models, especially XGBoost, showed moderate accuracy in identifying DR stages, suggesting that integrating these risk factors into clinical practice may improve early detection and intervention strategies for DR.

A Preliminary Report Regarding the Morphological Changes of Nano-Enabled Pharmaceutical Formulation on Human Lung Carcinoma Monolayer and 3D Bronchial Microtissue.

Background and Objectives: Nowadays, the development of enabled pharmaceutical nanoparticles of solid lipid type is continuously growing, because they have the potential to be used for targeted drug release leading to an increased effect of chemotherapy, being used in lung cancer nano-diagnosis and nano-therapy. The current study reports the preliminary results obtained regarding the biological effect of a new nano-enabled pharmaceutical formulation in terms of its cytotoxic and biosafety profile. Materials and Methods: The pharmaceutical formulations consist of solid lipid nanoparticles (SLN) obtained via the emulsification-diffusion method by loading green iron oxide nanoparticles (green-IONPs) with a pentacyclic triterpene (oleanolic acid-OA). Further, a complex biological assessment was performed, employing three-dimensional (3D) bronchial microtissues (EpiAirwayTM) to determine the biosafety profile of the SLN samples. The cytotoxic potential of the samples was evaluated on human lung carcinoma, using an in vitro model (A549 human lung carcinoma monolayer). Results: The data revealed that the A549 cell line was strongly affected after treatment with SLN samples, especially those that contained OA-loaded green-IONPs obtained with Ocimum basilicum extract (under 30% viability rates). The biosafety profile investigation of the 3D normal in vitro bronchial model showed that all the SLN samples negatively affected the viability of the bronchial microtissues (below 50%). As regards the morphological changes, all the samples induce major changes such as loss of the surface epithelium integrity, loss of epithelial junctions, loss of cilia, hyperkeratosis, and cell death caused by apoptosis. Conclusions: In summary, the culprit for the negative impact on viability and morphology of 3D normal bronchial microtissues could be the too-high dose (500 µg/mL) of the SLN sample used. Nevertheless, further adjustments in the SLN synthesis process and another complex in vitro evaluation will be considered for future research.

Recent Advances in Diagnosis and Treatment Approaches in Fungal Keratitis: A Narrative Review.

Fungal keratitis represents a potentially sight-threatening infection associated with poor prognosis, as well as financial burden. Novel diagnostic methods include polymerase-chain-reaction (PCR)-based approaches, metagenomic deep sequences, in vivo confocal microscopy, and antifungal susceptibility testing. The ideal therapeutic approaches and outcomes have been widely discussed in recent times, with early therapy being of the utmost importance for the preservation of visual acuity, minimizing corneal damage and reducing the scar size. However, combination therapy can be more efficacious compared to monotherapy. Understanding the pathogenesis, early diagnosis, and prevention strategies can be of great importance. In this narrative, we discuss the recent progress that may aid our understanding of the diagnosis, treatment, and prevention of mycotic keratitis.

Aldose Reductase as a Key Target in the Prevention and Treatment of Diabetic Retinopathy: A Comprehensive Review.

The escalating global prevalence of diabetes mellitus (DM) over the past two decades has led to a persistent high incidence of diabetic retinopathy (DR), necessitating screening for early symptoms and proper treatment. Effective management of DR aims to decrease vision impairment by controlling modifiable risk factors including hypertension, obesity, and dyslipidemia. Moreover, systemic medications and plant-based therapy show promise in advancing DR treatment. One of the key mechanisms related to DR pathogenesis is the polyol pathway, through which aldose reductase (AR) catalyzes the conversion of glucose to sorbitol within various tissues, including the retina, lens, ciliary body and iris. Elevated glucose levels activate AR, leading to osmotic stress, advanced glycation end-product formation, and oxidative damage. This further implies chronic inflammation, vascular permeability, and angiogenesis. Our comprehensive narrative review describes the therapeutic potential of aldose reductase inhibitors in treating DR, where both synthetic and natural inhibitors have been studied in recent decades. Our synthesis aims to guide future research and clinical interventions in DR management.

Double Anterior Interventricular Arteries: Prevalence and Morphological Types-A Dissection Study.

BACKGROUND: This study aimed to evaluate the prevalence of double anterior interventricular artery using the dissection method. METODE: A retrospective study was conducted between 2010 and 2024 at the Anatomy and Embryology Laboratory of the Victor Babes University of Medicine and Pharmacy in Timisoara. Eighty cases were analyzed for morphological variants of the coronary arteries, especially the anterior interventricular artery. RESULTS: Two cases of double anterior interventricular arteries were identified. In the first case, the two anterior interventricular arteries originated from the anterior interventricular branch of the left coronary artery. In the second case, an additional anterior interventricular artery with an aortic origin was found running along the lower third of the two interventricular grooves. This shape has not been described before in the specialized literature. CONCLUSIONS: Knowing the potential variations of the double left anterior descending artery is critical for interpreting cardiac imaging and choosing and planning percutaneous and surgical reperfusion strategies.

Human Ocular Toxoplasmosis in Romania: History, Epidemiology, and Public Health: A Narrative Review.

Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii (T. gondii), presents a significant global health concern, particularly for immunocompromised individuals and congenitally infected newborns. Despite its widespread prevalence, there are limited data on T. gondii seroprevalence and ocular toxoplasmosis in Romania. This review aims to summarize the research accomplished on the prevalence and epidemiology of human ocular toxoplasmosis in Romania. Ocular toxoplasmosis, a leading cause of infectious posterior uveitis worldwide, involves complex interactions between host immune responses and parasite factors. Clinically, it presents as focal necrotizing retinitis, characterized by active focal retinal lesions with adjacent chorioretinal scarring, often accompanied by vitreous inflammation and anterior chamber reactions. Diagnosis relies on clinical examination supported by fundus photography, optical coherence tomography (OCT), and serological assays. The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, conducting a literature review on PubMed, Google Scholar, and Scopus. Our focus was on ocular toxoplasmosis in Romania, and we used keywords and specific MeSH terms. Finally, 17 articles met all the criteria, as summarized in the PRISMA diagram. This study underscores the need for improved diagnostic methods, increased research efforts, and comprehensive public health education to mitigate the burden of toxoplasmosis and ocular toxoplasmosis in Romania.

The Great Saphenous Vein Proximal Part: Branches, Anatomical Variations, and Their Implications for Clinical Practice and Venous Reflux Surgery.

The anatomical variations in the lower limb veins play a critical role in venous reflux surgeries. This study presents an analysis of the great saphenous vein (GSV) proximal part's anatomical peculiarities, with 257 patients included, who were operated for venous reflux. This study highlighted a progressive increase in the GSV diameter in conjunction with the complexity of the anatomical variations, ranging from no tributaries to more than five tributaries, an anterior accessory GSV, or venous aneurysms. Statistical analysis evidenced this expansion to be significantly correlated with the variations. Additionally, the progression of the chronic venous disease (CVD) stages was notably more prevalent in the complex anatomical variations, suggesting a nuanced interplay between the GSV anatomy and CVD severity. Conclusively, our research articulates the paramount importance of recognizing GSV anatomical variations in optimizing surgical outcomes for CVD patients. These insights not only pave the way for enhanced diagnostic accuracy but also support the strategic framework within which surgical and interventional treatments are devised, advocating for personalized approaches to venous reflux surgery.

Comprehensive in vitro and in ovo assessment of cytotoxicity: Unraveling the impact of sodium fluoride, xylitol, and their synergistic associations in dental products.

Over the past several decades, dental health products containing fluoride have been widely employed to mitigate tooth decay and promote oral hygiene. However, concerns regarding the potential toxicological repercussions of fluoride exposure have incited continuous scientific inquiry. The current study investigated the cytotoxicity of sodium fluoride (NaF) and xylitol (Xyl), both individually and in combination, utilizing human keratinocyte (HaCaT) and osteosarcoma (SAOS-2) cell lines. In HaCaT cells, NaF decreased proliferation in a concentration-dependent manner and induced apoptosis-related morphological changes at low concentrations, whereas Xyl exhibited dose-dependent cytotoxic effects. The combination of NaF and Xyl reduced cell viability, particularly at higher concentrations, accompanied by apoptosis-like morphological alterations. Sub-cytotoxic NaF concentrations (0.2%) significantly affected caspase activity and the expression of pro-apoptotic genes. Conversely, Xyl demonstrated no discernible effect on these biological parameters. In SAOS-2 cells, NaF increased proliferation at high concentrations, contrasting with Xyl's concentration-dependent cytotoxic effects. The combination of NaF and Xyl had a minimal impact on cell viability. Sub-cytotoxic NaF concentrations did not influence caspase activity or gene expression, while Xyl induced dose-dependent morphological alterations, increased caspase activity, and upregulated pro-apoptotic gene expression. In ovo experiments on the chorioallantoic membrane (CAM) revealed that only NaF induced irritant effects, suggesting potential vascular adverse outcomes. This study advocates for the combined use of NaF and Xyl, highlighting their cytotoxicity benefits in healthy cells while maintaining safety considerations for tumor cells.

Immune-Mediated Ocular Surface Disease in Diabetes Mellitus-Clinical Perspectives and Treatment: A Narrative Review.

Diabetes mellitus (DM) is a chronic metabolic disorder marked by hyperglycemia due to defects in insulin secretion, action, or both, with a global prevalence that has tripled in recent decades. This condition poses significant public health challenges, affecting individuals, healthcare systems, and economies worldwide. Among its numerous complications, ocular surface disease (OSD) is a significant concern, yet understanding its pathophysiology, diagnosis, and management remains challenging. This review aims to explore the epidemiology, pathophysiology, clinical manifestations, diagnostic approaches, and management strategies of diabetes-related OSD. The ocular surface, including the cornea, conjunctiva, and associated structures, is vital for maintaining eye health, with the lacrimal functional unit (LFU) playing a crucial role in tear film regulation. In DM, changes in glycosaminoglycan metabolism, collagen synthesis, oxygen consumption, and LFU dysfunction contribute to ocular complications. Persistent hyperglycemia leads to the expression of cytokines, chemokines, and cell adhesion molecules, resulting in neuropathy, tear film abnormalities, and epithelial lesions. Recent advances in molecular research and therapeutic modalities, such as gene and stem cell therapies, show promise for managing diabetic ocular complications. Future research should focus on pathogenetically oriented therapies for diabetic neuropathy and keratopathy, transitioning from animal models to clinical trials to improve patient outcomes.

Clinical Consideration of Anatomical Variations in the Common Hepatic Arteries: An Analysis Using MDCT Angiography.

PURPOSE: The purpose of this study was to determine the prevalence of normal hepatic vascularization and variations in the common hepatic arteries using multidetector computer tomography angiography. These variants should be acknowledged before any surgery of the upper abdomen. The aim of our work was to analyze the variations in the hepatic arteries and their possible clinical and surgical implications. MATERIALS AND METHODS: This study was carried out on 4192 patients who underwent 64-slice MDCT angiography, from August 2015 to December 2021. We used surface and volume-rendering techniques in order to post-process images of the vascular components in the desired area. RESULTS: We highlighted 76 cases with replaced common hepatic arteries, which are characterized by the origin of the common hepatic artery trunk located outside the classical composition of the celiac trunk. We identified three levels of origin: the abdominal aorta, the superior mesenteric artery and the left gastric artery. We observed six different aspects of the morphological variability of the celiac trunk and the superior mesenteric artery. The trajectory of the artery trunk, between the aortic origin and the hepatic pedicle portion of the hepatic portal vein, is variable and we analyzed the pancreatic trajectory accordingly. CONCLUSIONS: The prevalence of hepatic arterial variants found during this study was similar to that in other specialized studies. We came across variants that have not been described in the well-known classification of Michels and even described extremely rare variations. The study of abnormal hepatic vascularization plays an important role in the surgical planning of hepatic transplantation, liver and pancreatic resection and extrahepatic upper abdominal surgeries.

Hepatic arterial variations detected at multidetector computer tomography angiography in the Romanian population.

BACKGROUND: Our purpose was to determine the prevalence of normal hepatic vascularization and variations of the hepatic arteries using multidetector computed tomography (MDCT) angiography. These variants should be known before any surgery of the upper abdomen, the downside being that there aren't many studies on large groups of patients using high-specialized imaging. MATERIALS AND METHODS: This study was carried out on 4192 patients. We performed MDCT angiography on each one of the patients and had a specialized team observe the images. RESULTS: Using Michels' classification, the normal anatomy (type I) was present in 3392 (80.91%) cases, while abnormal hepatic arteries were observed in 800 (19.08%) cases. The variations were distributed as follows: type II in 40 (0.95%) cases, type III in 442 (10.54%) cases, type IV in 13 (0.31%) cases, type V in 285 (6.79%) cases, type VI in 12 (0.28%) cases, type VII in 3 (0.07%) cases, type VIII in 108 (2.57%) cases, type IX in 6 (0.14%) cases and type X in one case (0.02%). 170 (4.05%) unclassified cases were observed. Using Hiatt's classification, the variations were: type II in 325 (7.75%) cases, type III in 454 (10.83%) cases, type IV in 124 (2.95%) cases, type V in 6 cases (0.14%) and type VI in 69 (1.64%) cases. 102 (2.43%) unclassified cases were observed. CONCLUSIONS: We observed well-known variations of the hepatic arterial pattern and also found a large number of rare, unclassified cases.

Changes in clinical and microbiological parameters of the periodontium during initial stages of orthodontic movement in patients with treated severe periodontitis: A longitudinal site-level analysis.

Applying orthodontic braces makes oral hygiene difficult and increases plaque accumulation, frequently resulting in gingival inflammation. In patients with previous severe periodontitis, this inflammation overlaps with the pre-existing inflammatory challenge and can lead to further progression of periodontal attachment loss. The aim of this study was to assess longitudinal site-level changes as mirrored by clinical and microbiological parameters during the initial remodeling of alveolar bone and the periodontal ligament, produced as an effect of light orthodontic forces in adult patients with severe periodontal disease that underwent standard (non-surgical and conventional surgical) periodontal therapy. Thirteen patients with previously treated severe generalized periodontitis were given fixed orthodontic appliances for re-alignment of teeth misaligned or displaced during the course of periodontitis. Before insertion of orthodontic appliances and at 2, 4, and 6 months of treatment, periodontal clinical parameters were recorded in the same deepest residual pocket of at least 3 mm in each patient. The same pocket was sampled at baseline and after 6 months of orthodontic treatment for the frequency of positive detection of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tanerella forsythia (Tf), Treponema denticola (Td). An average reduction in Pocket Depth by 0.2 mm at the end of the assessment period was identified. The only clinical parameter with statistically significant improvement was bleeding on probing. The frequency of detection of Aa, Pg, Pi, and Tf was not significantly different between baseline and 6 months of treatment, while a marginally significant increase of Td was found. There were no significant differences in the clinical parameters or microflora in the initial phase of orthodontic treatment in patients with reduced periodontal support. By correlating clinical and microbiological data, we concluded that the presence of periopathogens do not negatively influence periodontal health during orthodontic treatment in adult patients treated for severe periodontitis.

Critical Overview of HER2 Assessement in Bladder Cancer: What Is Missing for a Better Therapeutic Approach?

BACKGROUND/AIM: To assess the concordance between IHC and FISH and its influence on tumor type, grade and lympho-vascular invasion (LVI). MATERIALS AND METHODS: HER2 immunohistochemistry (IHC) to 45 cases of bladder carcinoma, followed by fluorescent in situ hybridization (FISH) were applied. RESULTS: 31.12% cases were IHC positive. Less than 35% of HER2-negative cases presented LVI and this percent increased to 54.54% for +1 HER2 cases. LVI increases up to 57.14% for +2 HER2 cases and slightly decreased for +3 HER2 cases to 42.85%. IHC/FISH concordance was found for 73.34% cases but 31.57% were previously negative and 36.36% scored as +1 by IHC had gene amplification as shown by FISH analysis. T3 was correlated with HER2-IHC (p=0.05) and HER2-FISH (p=0.01). CONCLUSION: Improved HER2 assessement is needed for urothelial carcinomas. HER2-IHC scored as 0-2 should be validated by and reclassified according to FISH analysis.

[Computer tomography in primary orbital tumors]. / Importanta examinarii computer tomografice în patologia tumorala primara a cavitatilor orbitale.

PURPOSE: The aim of this study is to observe the anatomical changes that occur in the tumoral pathology of the orbit, as well as to underline the importance of computed tomographic examination in the investigation of the orbital tumoral pathology. MATERIAL AND METHOD: This study has been conducted in the Military Hospital of Timisoara by a team made of anatomists, radiologists and ophthalmologists. A number of 215 patients were examined over a period of six years, between 1998-2002. The computed tomography examinations were made with Picker IQ Premier equipment, using contiguous native axial sections of 2 to 5 mm thick, after intravenous injection of non-ionic contrast-enhancing substance for vascular identification and iodophilic quantification specific to each structure. RESULTS: From the 215 patients that had undergone a CT examination of the orbits, 41 cases had positive orbital tumoral pathology. The primary tumors of the optic nerve had the highest incidence being present in 12 cases, of which 9 with glioma and 3 with meningioma. The second most frequent were the vascular tumors revealed in 11 cases. CONCLUSION: Due to its diagnosis performances CT has to be considered as a routine investigation method, recommended as a method of choice in orbital tumoral pathology.