OBJECTIVE: Brain metastases (BM) often leave residual tumors despite having visible margins, which increases the risk of local tumor recurrence and can impact overall patient survival rates. Fluorescence-guided surgery (FGS) utilizing sodium fluorescein (FL) has been reported as an effective technique in recent studies. This study aimed to evaluate the efficacy of FL FGS in improving the extent of resection of brain metastases and its impact on overall survival.
METHODS: We conducted a systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Our primary focus was on gross total resection (GTR). Additionally, we extracted survival data and evaluated the risk of bias using a modified version of the Joanna Briggs Institute critical appraisal tool.
RESULTS: The study comprised 970 patients with brain metastases through eight different studies. The study found that patients who underwent FL-guided resection had a significantly higher rate of GTR (OR: 2.02, 95% CI: 1.14-3.56, p = 0.0156, I2 = 41.5%). Additionally, the study concluded that FL-guided resection is associated with better overall survival rates (HR: 0.61, 95%CI: 0.47 0.80, p = 0.0003, I2 = 41.5%).
CONCLUSIONS: Our research suggests that the use of FL is associated with a higher rate of GTR and improved overall patient survival. None of the studies we reviewed reported significant complications associated with the use of FL in patients.

MoO3-x NPs was rapidly synthesized at room temperature by an easy stirring method. It was interesting to find that MoO3-x NPs induce OH- to generate active free radicals (ROS), which is a highly promising property in chemiluminescence (CL). Benefiting from the abundant oxygen vacancy, MoO3-x NPs adsorbs H2O2 and turn it into ·OH. The oxidase activity of fluorescein under visible light had already been reported, which catalyzes dissolved oxygen to become O2-· and continue to convert to H2O2. By creating the synergy effect with fluorescein, MoO3-x NPs strengthen the CL intensity of K3[Fe(CN)6]-fluorescein system significantly. Utilizing the quench effect of uric acid for the CL intensity, we developed a rapid, simple, and highly sensitive CL platform for uric acid detection. The linear range was 5-80 µM and the detection limit (LOD) for uric acid was 3.11 µM (S/N = 3). This work expanded the application of MoO3-x NPs in the CL field and developed a simple and highly sensitive CL sensing system to detect UA in human saliva.

Type 2 Diabetes Mellitus (T2DM) is linked to multiple complications, including cognitive impairment, and the prevalence of memory-related neurodegenerative diseases is higher in T2DM patients. One possible theory is the alteration of the microvascular and macrovascular environment of the blood-brain barrier (BBB). In this study, we employed different approaches, including RT-PCR, functional pharmacokinetic studies using sodium fluorescein (NaFL), and confocal microscopy, to characterize the functional and molecular integrity of the BBB in a T2DM animal model, leptin receptor-deficient mutant mice (Leprdb/db mice). As a result, VCAM-1, ICAM-1, MMP-9, and S100b (BBB-related markers) dysregulation was observed in the Leprdb/db animal model compared to littermate wild-type mice. The brain concentration of sodium fluorescein (NaFL) increased significantly in Leprdb/db untreated mice compared to insulin-treated mice. Therefore, the permeability of NaFL was higher in Leprdb/db control mice than in all remaining groups. Identifying the factors that increase the BBB in Leprdb/db mice will provide a better understanding of the BBB microvasculature and present previously undescribed findings of T2DM-related brain illnesses, filling knowledge gaps in this emerging field of research.

The complexity of intracranial anatomy and pathologies warrants the optimization of multimodal techniques to ensure safe and effective surgical treatment. Endoscopy is being more widely implemented in intracranial procedures as an important visualization tool, as it can offer panoramic views of deep structures while reducing the invasiveness of approaches. Fluorophores are frequently utilized to augment the identification of intracranial anatomic landmarks and pathologies. This chapter discusses the integration of these two surgical adjuncts, highlighting the key fluorophores used in endoscopic neurosurgery and their clinical applications.

OBJECTIVE: Indocyanine green (ICG) and sodium fluorescein (Na-Fl) are two fluorophores, which are used for videoangiography purposes. This prospective study reports our experience by using surgical microscopes equipped with two special filters. We compared the imaging efficacy of Na-FL and ICG videoangiography techniques during aneurysm and arteriovenous malformations (AVM) surgeries.
METHODS: Fourtynine consecutive patients were operated between September 2015 and December 2022. Patients with ruptured/unruptured aneurysms or with AVMs presented with/without hemorrhage were included to the current study.
RESULTS: There were a total of 48 aneurysms and 11 AVMs in 49 patients in the current study. Na-Fl enables the surgeon to manipulate vessels and aneurysms real-time. ICG provides the ability to watch the videoangiography repeatedly and understand the angioarchitecture. The use of FLOW-800 module allows the surgeon to make concrete judgements about the flow dynamics of AVMs and therefore ICG videoangiography found useful in AVM surgery. Na-Fl has been found more useful for the evalution of the low caliber perforating arteries and anatomical features of the aneursym dome in aneurysm surgery.
CONCLUSIONS: The results of our series demonstrated the safety and efficacy of Na-Fl use in the surgery of aneurysms and AVMs. Both the ICG and Na-Fl videoangiographies are easy to perform and complimentary to each other. Combined use of these two mediums may provide better surgical results, considering the separate advantages and disadvantages of these both techniques.

OBJECTIVE: Recurrent cerebrospinal fluid (CSF) rhinorrhea caused by sequential, anatomically separated skull base defects is rarely reported in the literature. Neither management nor etiology has been sufficiently investigated. We present an illustrative case and a systematic review of the literature regarding etiology, diagnostics, and management of this rare phenomenon.
METHODS: A systematic literature search looking for articles reporting sequential CSF leaks with multiple skull base defects was performed. Data from included articles were descriptively reported, and the quality of the included studies was assessed with Grading of Recommendations Assessment, Development and Evaluation.
RESULTS: A 71-year-old woman with posttraumatic CSF rhinorrhea and left-sided CSF otorrhea due to a left-sided horizontal fracture of the petrous bone presented at our institution. After initial surgical repair and a 10-week symptom-free interval, CSF rhinorrhea recurred. Imaging revealed a preexisting contralateral meningoencephalocele of the lateral sphenoid recess causing recurrent CSF rhinorrhea most likely after initial traumatic laceration. The defect was successfully treated. A literature search identified 366 reports, 6 of which were included in the systematic review with a total of 10 cases. Quality was deemed good in 8 of 10 cases. The most common location for primary and sequential CSF leaks was along the sphenoid bone (4/10 and 5/10 patients, respectively). All publications except one reported the presence of a meningo (encephalo)cele as cause of the sequential CSF leak.
CONCLUSIONS: Occurrence of recurrent CSF rhinorrhea due to an anatomically separated sequential skull base lesion remains a rare phenomenon. Reassessment of imaging studies and a structured diagnostic workup to detect sequential CSF leaks independent of the primary lesion should is recommended.

OBJECTIVE: To compare the ocular surface disease index (OSDI) questionnaire with objective tests in dry eye disease.
METHODS: A prospective observational study. Place and Duration of the Study: Department of Ophthalmology, Nigde Omer Halisdemir University, Nigde, Turkiye, from 9th June to 31st December 2022.
METHODS: All clinically diagnosed 323 eyes of patients with dry eye disease (DED) were included. The subjects were evaluated by the Oxford classification of corneal and conjunctival fluorescein staining, Schirmer I test, and fluorescein tear breakup time (TBUT). Symptoms of the patients were interpreted with OSDI and correlations of symptoms and objective markers were analysed.
RESULTS: There was no significant association between any objective signs (Schirmer I, TBUT, and Oxford), and OSDI (p = 0.26, 0.52, 0.18, and respectively). Schirmer I score showed a significant positive correlation with TBUT (p <0.001, r = 0.21) and a significant negative correlation with Oxford scale (p <0.001, r = -0.19). There was a statistically negative correlation between TBUT and Oxford scale (p <0.001, r = -0.37).
CONCLUSIONS: Except for the Schirmer test, TBUT and Oxford scale are effective tools in the diagnosis of DED. Symptom markers, such as OSDI may have lower reliability in diagnosing DED and determining its severity. Diagnostic tests are important in the detection of asymptomatic or less severe dry eye disease that can be ignored.
BACKGROUND: Dry eye disease, Diagnosis, Ocular surface disease index (OSDI), Tear breakup time (TBUT), Oxford grading scale, Schirmer I test.

Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated Protein (CRISPR-Cas) systems have evolved several mechanisms to specifically target foreign DNA. These properties have made them attractive as biosensors. The primary drawback associated with contemporary CRISPR-Cas biosensors is their weak signaling capacity, which is typically compensated for by coupling the CRISPR-Cas systems to nucleic acid amplification. An alternative strategy to improve signaling capacity is to engineer the reporter, i.e., design new signal-generating substrates for Cas proteins. Unfortunately, due to their reliance on custom synthesis, most of these engineered reporter substrates are inaccessible to many researchers. Herein, we investigate a substrate based on a fluorescein (FAM)-tetramethylrhodamine (TAMRA) Förster resonant energy-transfer (FRET) pair that functions as a seamless \"drop-in\" replacement for existing reporters, without the need to change any other aspect of a CRISPR-Cas12a-based assay. The reporter is readily available and employs FRET to produce two signals upon cleavage by Cas12a. The use of both signals in a ratiometric manner provides for improved assay performance and a decreased time-to-result for several CRISPR-Cas12a assays when compared to a traditional FAM-Black Hole Quencher (BHQ) quench-based reporter. We comprehensively characterize this reporter to better understand the reasons for the improved signaling capacity and benchmark it against the current standard CRISPR-Cas reporter. Finally, to showcase the real-world utility of the reporter, we employ it in a Recombinase Polymerase Amplification (RPA)-CRISPR-Cas12a DNA Endonuclease-Targeted CRISPR Trans Reporter (DETECTR) assay to detect Human papillomavirus in patient-derived samples.

BACKGROUND: The use of fluorescent technologies in vascular neurosurgery emerged after indocyanine green video angiography (ICG-VA) was first described in 2003. As data supporting the efficiency of ICG in preventing postoperative complications has grown substantially, it has now established itself as the standard of care. However, the predominant literature centers on ICG techniques, leaving the evaluation of cost-effective fluorescein tools pending. We report the results of a prospective study in which we demonstrated the impact of intraoperative fluorescein videoangiography (FL-VA) in aneurysm surgery.
METHODS: Between December 2021 and September 2022, a total of 57 patients underwent craniotomy for intracranial aneurysm surgery. After aneurysm clipping, we administered a 0.5 mg/Kg of sodium fluorescein, and the intracranial area of interest was inspected through the microscope integrated module. The following data were collected: patient age and sex; number of clipped aneurysms; aneurysm location, size, and rupture status; Hunt Hess grade; intraoperative rupture; aneurysm calcification and thrombosed aneurysm; visualization of blood flow in perforating arteries; need for a clip adjustment after FL-VA analysis by neurosurgeon.
RESULTS: For the surgical clipping of 64 aneurysms in 57 patients, 80 FL-VA studies were performed. Clip adjustments were performed following FL-VA in 13 aneurysms. FL-VA had an impact on 20 % of the clipping. In seven aneurysms, clip adjustment was due to the \"presence of residual aneurysm\", in three cases due to the \"presence of neck\", and in three cases due to \"adjacent vessel stenosis\". Regarding the evaluation of flow in the perforating vessels, it was possible, with a good and detailed image in all cases.
CONCLUSIONS: The use of FL-VA has a significant impact in aneurysm surgery, enhancing effectiveness and safety. The dosage of 0.5 mg/kg administered is sufficient for assessing both aneurysm occlusion and the presence of flow in adjacent vessels.

To establish the correlation between thermal conditions imposed on bloodstains and visualizing effect of enhancement techniques, infrared photography and four chemical enhancement reagents were used to visualize bloodstains following thermal exposure. A black tile was selected as the substrate to intensify the visualization challenge, with a Cone Calorimeter serving as the standardized heating source to control thermal conditions. Compared with standard photography, infrared photography is proven to be a valuable complement to chemical reagents, showing significant advantages in visualizing bloodstains after thermal exposure. However, it is worth noting that infrared image fell short of standard image when bloodstains displayed raised, embossed morphology or when bloodstains almost disappeared under specific conditions. The enhancement effectiveness was found to be strongly correlated with thermal conditions imposed on bloodstains, and the morphology evolution of bloodstains during heating affected the chemical enhancement effect additionally, especially when the bulge morphology was formed, and it was observed that reagents were more effective after removing the dense shell of the bulge. Among the four selected chemical enhancement reagents, fluorescein performed exceptionally well, maintaining its effectiveness even for bloodstains heated at 641°C for 10 min. TMB demonstrated its visualizing ability for bloodstains heated at 396°C for 5 min and heated at 310°C for 20 min. BLUESTAR® followed afterwards, while luminol performed worst. The correlation between thermal conditions imposed on bloodstains and the corresponding visualizing effectiveness of enhancement techniques provides important references for detecting bloodstains at fire scenes.