Oxidative Stress in the Pathogenesis of Oral Cancer.

Oxidative stress, arising from an imbalance between reactive oxygen species (ROS) and antioxidants, contributes significantly to oral cancer such as oral squamous cell carcinoma (OSCC) initiation, promotion, and progression. ROS, generated both internally and externally, induce cellular damage including DNA mutations and lipid peroxidation, fostering oncogene activation and carcinogenesis. The objective of this review was to cover and analyze the interplay between ROS and antioxidants, influencing the key processes such as cell proliferation, apoptosis, and angiogenesis, shaping the trajectory of OSCC development. Despite the promise of antioxidants to halt cancer progression and mitigate oxidative damage, their therapeutic efficacy remains debated. The conducted literature search highlighted potential biomarkers that indicate levels of oxidative stress, showing promise for the early detection and monitoring of OSCC. Furthermore, melatonin has emerged as a promising adjunct therapy for OSCC, exerting antioxidant and oncostatic effects by modulating tumor-associated neutrophils and inhibiting cancer cell survival and migration. In addition, this review aims to shed light on developing personalized therapeutic strategies for patients with OSCC such as melatonin therapy, which will be discussed. Research is needed to elucidate the underlying mechanisms and clinical implications of oxidative stress modulation in the context of oral cancer.

Depression in Rheumatoid Arthritis: Prevalence and Effects on Disease Activity.

Background:The primary objective of this study was to estimate depression's prevalence in a cohort of rheumatoid arthritis (RA) patients, and the secondary objective was to evaluate the impact of depression on disease activity over time. Methods: We included all patients with RA presenting to our clinic from 2019 to 2020, who had three follow-up visits available. Depression prevalence was calculated using the patient's history of diagnosed depression, and disease activity was assessed using the disease activity score for 28 joints (DAS28) and its components: tender joint count (TJC), swollen joint count (SJC), pain value on a visual analog scale (VAS), and inflammatory markers. Results: A total of 400 RA patients were included, 75 of whom had diagnosed depression, generating a prevalence of 18.8%. The mean values of DAS28 and its components were higher, with statistical significance, in the depression subgroup at all three follow-ups (p < 0.001). Conclusions: Depression is prevalent in the RA population, and leads to higher disease activity in dynamic evaluations. Assessing depression could be a psychological marker for RA prognosis with an important outcome in controlling disease activity.

KRAS mutations and endometriosis burden of disease.

The clinical phenotype of somatic mutations in endometriosis is unknown. The objective was to determine whether somatic KRAS mutations were associated with greater disease burden in endometriosis (i.e. more severe subtypes and higher stage). This prospective longitudinal cohort study included 122 subjects undergoing endometriosis surgery at a tertiary referral center between 2013 and 2017, with 5-9 years of follow-up. Somatic activating KRAS codon 12 mutations were detected in endometriosis lesions using droplet digital PCR. KRAS mutation status for each subject was coded as present (KRAS mutation in at least one endometriosis sample in a subject) or absent. Standardized clinical phenotyping for each subject was carried out via linkage to a prospective registry. Primary outcome was anatomic disease burden, based on distribution of subtypes (deep infiltrating endometriosis, ovarian endometrioma, and superficial peritoneal endometriosis) and surgical staging (Stages I-IV). Secondary outcomes were markers of surgical difficulty, demographics, pain scores, and risk of re-operation. KRAS mutation presence was higher in subjects with deep infiltrating endometriosis or endometrioma lesions only (57.9%; 11/19) and subjects with mixed subtypes (60.6%; 40/66), compared with those with superficial endometriosis only (35.1%; 13/37) (p = 0.04). KRAS mutation was present in 27.6% (8/29) of Stage I cases, in comparison to 65.0% (13/20) of Stage II, 63.0% (17/27) of Stage III, and 58.1% (25/43) of Stage IV cases (p = 0.02). KRAS mutation was also associated with greater surgical difficulty (ureterolysis) (relative risk [RR] = 1.47, 95% CI: 1.02-2.11) and non-Caucasian ethnicity (RR = 0.64, 95% CI: 0.47-0.89). Pain severities did not differ based on KRAS mutation status, at either baseline or follow-up. Re-operation rates were low overall, occurring in 17.2% with KRAS mutation compared with 10.3% without (RR = 1.66, 95% CI: 0.66-4.21). In conclusion, KRAS mutations were associated with greater anatomic severity of endometriosis, resulting in increased surgical difficulty. Somatic cancer-driver mutations may inform a future molecular classification of endometriosis.

Depression in Rheumatoid Arthritis: A Narrative Review-Diagnostic Challenges, Pathogenic Mechanisms and Effects.

Depression is one of the most frequent comorbidities in rheumatoid arthritis (RA); it takes an important toll on the quality of life of these patients and also leads to a decrease in life expectancy. The current article is a narrative review on depression in RA, with the objective to emphasize and raise awareness on the high prevalence, pathogenic mechanisms, and effects that depression has on RA patients. In RA, the prevalence of depression has been shown to be 2 to 3 times higher than in the general population, with a meta-analysis reporting that 16.8% of RA patients have a major depressive disorder. Future studies are needed to determine the most accurate self-reported depression questionnaires and their ideal threshold for defining depression as compared to diagnostic interview as gold-standard for patients with RA to allow better comparisons across studies. The pathogenesis of depression remains to be fully understood, but recent specialty literature suggests that immune-mediated processes are involved and that there are similarities between the neural networks recruited in inflammation and those implicated in the pathophysiology of depression. Depression in patients with RA is associated with poor long-term outcomes. Multiple studies have shown that depression in RA is associated with increased pain, fatigue, and physical disability. It alters treatment compliance, causes more comorbidities, and leads to higher mortality, partly through increased suicide risk. Depression in RA also increases health service utilization and healthcare costs directly through hospitalization, but also indirectly through loss of work productivity. Assessing depression could be a significant psychomarker of rheumatological outcome in RA.

The Angiogenic Balance and Its Implications in Cancer and Cardiovascular Diseases: An Overview.

Angiogenesis is the process of developing new blood vessels from pre-existing ones. This review summarizes the main features of physiological and pathological angiogenesis and those of angiogenesis activation and inhibition. In healthy adults, angiogenesis is absent apart from its involvement in female reproductive functions and tissue regeneration. Angiogenesis is a complex process regulated by the action of specific activators and inhibitors. In certain diseases, modulating the angiogenic balance can be a therapeutic route, either by inhibiting angiogenesis (for example in the case of tumor angiogenesis), or by trying to activate the process of new blood vessels formation, which is the goal in case of cardiac or peripheral ischemia.

Pathways in the synthesis of functionalized glycolipids for liposomal preparations.

We describe in this paper the synthesis of two glycolipids containing a mannosyl residue functionalized with malonic acid and azide groups at the C6 position. Two synthetic routes have been successfully implemented: the first one involves Schmidt's glycosylation procedure using functionalized carbohydrates, whereas the second one involves nucleophilic substitutions in the C6 position of an iodinated intermediate obtained using Koenigs-Knorr reaction. A comparative discussion of reactions and yields is realized. The two glycolipids served as material for the preparation of liposomes.

Ultrasound biomicroscopy in glaucoma assessment.

Ultrasound biomicroscopy (UBM) is an important tool in the diagnosis, evaluation and follow up of glaucoma patients. Even if we are dealing with a primary angle closure glaucoma (PACG) or a primary open angle glaucoma (POAG) patient, the mechanism of angle closure can be revealed by performing an UBM. The device can help differentiate between the two types of glaucoma even in patients with opaque corneas when gonioscopy cannot be performed. Knowing the type of glaucoma is vital, especially regarding an individualized treatment, since each patient is unique and needs to be treated accordingly, in order to prevent glaucomatous optic neuropathy and visual field loss. Abbreviations: AC = anterior chamber, ICE = iridocorneal endothelial syndrome, IOP = intraocular pressure, NTG = normal tension glaucoma, PACG = primary angle closure glaucoma, PC = posterior chamber, PEX = pseudoexfoliation syndrome, POAG = primary open angle glaucoma, UBM = ultrasound biomicroscopy.

Update on Myopia Risk Factors and Microenvironmental Changes.

The focus of this update is to emphasize the recent advances in the pathogenesis and various molecular key approaches associated with myopia in order to reveal new potential therapeutic targets. We review the current evidence for its complex genetics and evaluate the known or candidate genes and loci. In addition, we discuss recent investigations regarding the role of environmental factors. This paper also covers current research aimed at elucidating the signaling pathways involved in the pathogenesis of myopia.

Ultrasound biomicroscopy as a vital tool in occult phacomorphic glaucoma.

Ultrasound is a fundamental tool used in all medical specialties, including ophthalmology. Nowadays, ultrasound biomicroscopy (UBM), a method with higher resolution, allows the investigation of in vivo details of the anterior segment of the eye at microscopic resolution. The examination is especially useful in patients with secondary glaucoma that involves a lens component such as phacomorphic glaucoma and occult phacomorphic glaucoma (OPG). The purpose of this paper was to familiarize audience with UBM and the importance of this investigation in OPG, by presenting a series of cases in which performing an UBM was vital because it provided the information needed in order to safely accomplish a curative surgical treatment that preserved our patients' visual acuity.

The importance of corneal assessment in a glaucoma suspect - a review.

Glaucoma represents the main cause of irreversible blindness in the world and for this consideration, the interest in a quick and precise diagnosis and progression of the disease, prior to the appearance of irreversible damage, has been continuously rising. Glaucoma risk factors are already well known, but current studies reveal that it is necessary to make a proper analysis of the intraocular pressure (IOP) to obtain an accurate diagnosis, so we must take into consideration corneal properties that might affect IOP measurements. Starting from corneal geometrical properties represented by central corneal thickness (CCT) and continuing with biomechanical properties represented by corneal hysteresis (CH) and corneal resistance factor (CRF) we reviewed the value of investigating corneal properties in ocular hypertension (OH), primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients. We can now say that CCT plays an important role in diagnosing glaucoma because it may mask the real value of the IOP and also, in setting the target for the IOP needed to stop disease progression. Also, CH is a factor that needs to be screened from the first consult of a glaucoma patient or suspect because it is correlated to the response to treatment, visual field (VF) and retinal nerve fiber layer (RNFL) progression and could anticipate the future evolution and patients prognosis. Both CCT and CH are factors that must be thought-about when we encounter a glaucoma suspect. CCT has a predictive role in OH and NTG patients, while CH has on the other hand a prognostic role in POAG, OH and NTG patients.

The ganglion cell complex as an useful tool in glaucoma assessment.

Glaucoma is known as an optic neuropathy prone to progression that determines characteristic not only structural (loss of the ganglion cells as well as their axons) but also functional defects (visual field loss). Objective: To evaluate the possibility of applying ganglion cell complex analysis (GCC) in patients who associate ocular hypertension with tilted disc and marked peripapillary atrophy. Methods: In order to evaluate its components, GCC can be investigated using the Optical Coherence Tomography (OCT) revealing: ganglion cell layer (cells bodies), inner plexiform layer (dendrites and synapses), and nerve fiber layer (axons). Our study included 196 eyes divided into 3 groups: 52 diagnosed with primary open angle glaucoma (POAG), 63 with ocular hypertension (OH), and 81 healthy (normal) eyes (NE). All eyes were submitted to a complete ophthalmologic checkup that involved advanced optic nerve and GCC evaluation. Results: A positive statistically significant correlation was identified between the GCC thickness and the RNFL in all three categories taken into account: R=0,6, p<0,0001 for glaucoma group, R=0,66, p<0,0001 for OH group and R=0,46, p<0,0001 for normal group. Conclusions: GCC has been proved useful for the assessment of the retinal nerve fiber layer (RNFL) in eyes with OH that associate tilted disc or peripapillary atrophy where the optic disc edges might not be certainly determined by the OCT.

The importance of ganglion cell complex investigation in myopic patients.

Glaucoma is an optic neuropathy that affects the ganglion cell complex in all its components: cell bodies, dendrites, and axons, the dendritic arbor being the first one damaged. This is the reason why the thickness of the ganglion cell and internal plexiform layers can be taken into account as an early predictor of the glaucomatous changes, along with the retinal nerve fiber layer (RNFL) thickness. However, due to disc tilting and peripapillary atrophy, the RNFL evaluation may be prone to errors in myopic patients. We presented the cases of two myopic patients, who, after a routine examination, were identified as glaucoma suspects. The Optical Coherence Tomography (OCT) scan revealed a nerve fiber loss which was not confirmed by the ganglion cell complex scan. Thereafter we manually adjusted the optic disc margins according to the patients' myopic changes and this time the retinal nerve fiber layer was also normal. We observed that the ganglion cell complex evaluation led to fewer errors than the retinal nerve fiber layer evaluation, particularly in front of a myopic patient. Nevertheless, various investigations should be considered in the attempt to issue a diagnosis of glaucoma.

Inflammatory Biomarkers Profile as Microenvironmental Expression in Keratoconus.

Keratoconus is a degenerative disorder with progressive stromal thinning and transformation of the normal corneal architecture towards ectasia that results in decreased vision due to irregular astigmatism and irreversible tissue scarring. The pathogenesis of keratoconus still remains unclear. Hypotheses that this condition has an inflammatory etiopathogenetic component apart from the genetic and environmental factors are beginning to escalate in the research domain. This paper covers the most relevant and recent published papers regarding the biomarkers of inflammation, their signaling pathway, and the potentially new therapeutic options in keratoconus.

Secondary congenital aphakia.

UNLABELLED: Abstract PURPOSE: We present the clinical, paraclinical and therapeutic features in a patient with secondary congenital aphakia. METHODS: A 2-year-old patient, diagnosed with congenital rubella syndrome including sensorineural deafness, congenital heart disease, intellectual disability, microcephaly, microphthalmia, and congenital cataract, presented to our clinic for the surgical treatment of cataract. RESULTS: During the surgery, the absence of the lens' cortex was observed, hence, the final diagnose was of secondary congenital aphakia. Surgery was then continued with a posterior capsulorhexis and an anterior vitrectomy, deciding to postpone the implantation of the posterior chamber intraocular lens.

New mannose derivatives: The tetrazole analogue of mannose-6-phosphate as angiogenesis inhibitor.

Two novel compounds with mannose-derived structure, bearing a tetrazole (compound 3) and a sulfone group (compound 4) in terminal position, have been prepared from methyl α-d-mannopyranoside in reduced number of steps. The angiogenic activity of 3 and 4 has been screened using the chick chorioallantoic membrane (CAM) method. Tetrazole 3 has been identified to possess a promising bioactivity, being identified as angiogenesis inhibitor, with 68% of neovascular vessels when compared to control (PBS).

The importance of assessing corneal biomechanical properties in glaucoma patients care - a review.

Purpose: to familiarize the public with the role of corneal biomechanics in glaucoma patient management. Methods: Ocular Response Analyzer (ORA) is the only device that measures in vivo corneal biomechanics. Recent studies regarding "corneal biomechanics and glaucoma" were reviewed and the obtained data were compared in order to present a better understanding of the corneal biomechanical properties involvement in glaucoma care. Results: According to the studies reviewed, in primary open angle glaucoma (POAG) the mean corneal hysteresis (CH) and the corneal resistance factor (CRF) were approximately 2 mmHg lower than in normal eyes. In ocular hypertension (OH), the mean CH was about 1mmHg higher than in POAG patients and 1mmHg lower than in the control group, while the mean CRF was about 2mmHg higher than in POAG and 1mmHg higher than in the control group. Regarding the normal tension glaucoma (NTG), there were studies that showed that the mean CH and CRF were approximately 1mmHg lower than in POAG and studies that showed similar values between the POAG and NTG groups. The mean CH did not differ much between POAG and angle closure glaucoma (ACG), being lower than in normal individuals, while CRF appeared to be higher in the ACG than in normal individuals. Concerning congenital glaucoma (CG), both CH and CRF were about 2mmHg lower than in normal eyes. Conclusions: Corneal biomechanics influenced the IOP measurement and have been proven to be of a great significance in glaucoma patients regardless of the central corneal thickness (CCT). Lower values of CH and CRF could suggest an alteration in the corneal response associated to glaucoma.

Correlations between Corneal Biomechanics and Glaucoma Severity in Patients with Primary Open Angle Glaucoma.

OBJECTIVES: To investigate the relationship between corneal biomechanical changes and glaucoma severity in primary open angle glaucoma patients. DESIGN: Correlation study. MATERIALS AND METHODS: Our study included 70 glaucomatous eyes; they were divided in groups using Glaucoma Staging System Based on Humphrey Visual Field. Ocular Response Analyzer (ORA) was used in order to determine corneal hysteresis (CH) and corneal resistance factor (CRF); ultrasonic pachimetry (Ocuscan) to measure central corneal thickness (CCT) and Humphrey Visual Analyser to determine mean deviation (MD), pattern standard deviation (PSD) and visual field index (VFI). For statistical analysis we used descriptive analysis and linear regression using IBM SPSS Statistics Standard. OUTCOMES: Out of the 70 eyes with primary open angle glaucoma examined that had visual acuity 0,7 or better, 35 were included in stage 1 (MD 0.01dB -> -6dB), 21 in stage 2 (MD -6.01dB -> -12dB) and 14 in stage 3 (MD -12.01dB -> -20dB). A considerable statistic correlation was found between CH and VFI both in the entire group of primary open angle glaucoma patients( r=0.44, p<0.001), and in stages 1 (r=0.44, p<0.009), 2 (r=0.51, p<0.01) and 3 (r=0.52, p<0.05). CONCLUSION: The study shows a moderate correlation, statistically significant, between corneal hysteresis and visual field index in glaucoma patients. Ocular response analyzer can be considered an useful instrument in evaluation of primary open angle glaucoma patients.

Retroperitoneal cystic lymphangioma in a patient with previous surgery for seminoma. A case report.

Retroperitoneal cystic lymphangioma is a rare disease, more frequent in children. The indication for resection is due to the presence of symptoms or compression of the neighboring organs. Hereby, it is described the case of an adult patient with previous surgery for seminoma. Complete resection of the tumor is the treatment of choice. The differential diagnosis in this particular situation is discussed.

[Limitations in the histopathologic diagnosis and prognosis of neuroblastoma]. / Limite în diagnosticul histopatologic si prognosticul neuroblastoamelor.

Neuroblastoma is the most common nonhematopoietic solid tumor of childhood and has been intensively studied for at least 4 decades. Despite this, few predictive histopathologic clues to its behavior exist. Ages, anatomic sites of occurrence, histopathology of the tumor and clinical stage have traditionally been the only reliable prognostic factors in this disease. In the present study we analyzed these prognostic factors in 72 neuroblastic tumors and our histopathological possibilities of diagnosis.