OBJECTIVE: Recurrent cerebrospinal fluid (CSF) rhinorrhea caused by sequential, anatomically separated skull base defects are rarely reported in the literature. Neither management nor etiology are sufficiently investigated. We herein 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 was descriptively reported, the quality of the included studies was assessed with GRADE.
RESULTS: A 71-year-old female patient with posttraumatic rhino- and left-sided otorrhea due to a left-sided longitudinal fracture of the petrous bone presented at our institution. After initial surgical repair and a ten-week symptom-free interval, CSF-rhinorrhea reoccurred. Imaging review revealed a pre-existing contralateral meningoencephalocele of the lateral sphenoid recess causing recurrent CSF-rhinorrhea most likely after initial traumatic laceration. The defect was successfully treated. Literature search identified 366 reports, six of which were included in the systematic review with a total of ten cases. Quality was deemed good in 8/10 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 yet described phenomenon. Reassessment of imaging studies and a structured diagnostic work-up to detect sequential CSF-leaks independent of the primary lesion should therefore be considered.

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.

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.

Controlled release of low molecular weight hydrophilic drugs, administered locally, allows maintenance of high concentrations at the target site, reduces systemic side effects, and improves patient compliance. Injectable hydrogels are commonly used as a vehicle. However, slow release of low molecular weight hydrophilic drugs is very difficult to achieve, mainly due to a rapid diffusion of the drug out of the drug delivery system. Here we present an injectable and self-healing hydrogel based entirely on the self-assembly of liposomes. Gelation of liposomes, without damaging their structural integrity, was induced by modifying the cholesterol content and surface charge. The small hydrophilic molecule, sodium fluorescein, was loaded either within the extra-liposomal space or encapsulated into the aqueous cores of the liposomes. This encapsulation strategy enabled the achievement of controlled and adjustable release profiles, dependent on the mechanical strength of the gel. The hydrogel had a high mechanical strength, minimal swelling, and slow degradation. The liposome-based hydrogel had prolonged mechanical stability in vivo with benign tissue reaction. This work presents a new class of injectable hydrogel that holds promise as a versatile drug delivery system. STATEMENT OF SIGNIFICANCE: The porous nature of hydrogels poses a challenge for delivering small hydrophilic drug, often resulting in initial burst release and shorten duration of release. This issue is particularly pronounced with physically crosslinked hydrogels, since their matrix can swell and dissipate rapidly, but even in cases where the polymers in the hydrogel are covalently cross-linked, small molecules can be rapidly released through its porous mesh. Here we present an injectable self-healing hydrogel based entirely on the self-assembly of liposomes. Small hydrophilic molecules were entrapped inside the extra-liposomal space or loaded into the aqueous cores of the liposomes, allowing controlled and tunable release profiles.

UNASSIGNED: Awake craniotomy (AC) maximizes the resection of lesions in eloquent brain areas while preserving functionality. Tumor delineation with intraoperative use of sodium fluorescein (NaFl) facilitates total resection. When used with AC, it may allow for safe resection without increasing the risk of postoperative neurologic deficits. This study investigated the efficacy and safety of the combined use of NaFl and AC for maximum safe resection in patients with brain metastases.
UNASSIGNED: Patients who underwent AC due to brain metastasis in the Department of Neurosurgery of Uludağ University\'s Faculty of Medicine between January 1, 2018 and August 1, 2022, were retrospectively analyzed. The study comprised 2 patient groups: plain AC (pAC) and NaFl-guided AC (NaFlg-AC). Surgical outcomes related to fluorescence intensity, degree of resection, perioperative complications, and postoperative neurological factors were evaluated.
UNASSIGNED: The pAC group included 16 patients (12 males, 4 females), and the NaFlg-AC group comprised 21 (13 males, 7 females). The mean patient ages for males and females were 61.4 years (61.4 ± 9.5 years) and 60.4 years (60.6 ± 12 years), respectively. The most common origin of the metastatic lesion was the lung in both the pAC and NaFlg-AC groups (n = 12 vs. n = 14, respectively). Gross total resection (GTR) was achieved in 85.7% of the patients in the NaFlg-AC group, whereas the GTR rate was 68.7% in the pAC group. There was no significant difference in GTR rates between the 2 groups (p = 0.254). The mean duration of the resection time was significantly shorter in the NaFlg-AC group (45.95 ± 7.00 min vs. 57.5 ± 12.51 min; p = 0.002). The patients\' Karnofsky Performance Status (KPS) score did not reach statistical significance at 6-month follow-up in either group compared to their preoperative baseline scores (p = 0.374). KPS did not show a significant difference between the 2 groups at any time.
UNASSIGNED: Fluorescence-guided resection in AC for metastatic tumors in sensory, motor, and cognitive areas is a feasible, safe, and convenient technique that significantly increases GTR rates and shortens operative time compared to conventional white light surgery without fluorescence guidance. It also does not increase the incidence of postoperative complications. With the combined use of AC and NaFl, ensuring clear and visible tumor margins during surgery and controlling patients\' neurological function in real-time are possible.

OBJECTIVE: The vital function of eloquent and deep brain areas necessitates precise treatment for tumors located in these regions. Fluorescein-guided surgery (FGS) has been widely used for high-grade gliomas (HGGs) resection. Nevertheless, the safety and efficacy of utilizing this technique for resecting brain tumors located in eloquent and deep-seated areas remain uncertain. This study aims to assess the safety and extent of resection of HGGs in these challenging tumors with fluorescein and explore its impact on patient survival.
METHODS: A retrospective analysis was conducted on the clinical and radiological data of 67 consecutive patients with eloquent or deep-seated HGGs who underwent surgery between January 2020 and June 2023. Lacroix functional location grade was used to determine the eloquence of the tumors. The comparison between the fluorescence-guided surgery group (FGS, n = 32) and the conventional white-light microscopic surgery group (non-FGS, n = 35) included assessments of extent of resection (EOR), rates of gross total resection (GTR, 100%) and near-total resection (NTR, 99 to 98%), postoperative Neurologic Assessment in Neuro-Oncology (NANO) scores, overall survival (OS), and progression-free survival (PFS), to evaluate the safety and efficacy of fluorescein-guided technology in tumor resection at these specific locations.
RESULTS: Baseline of demographics, lesion location, and pathology showed no significant difference between the two groups. GTR of the FGS group was higher than the non-FGS group (84.4% vs. 60.0%, OR 3.60, 95% CI 1.18-10.28, p < 0.05). The FGS group also showed higher GTR + NTR (EOR ≥ 98%) than the non-FGS group (93.8% vs. 65.7%, OR 7.83, 95% CI 1.86-36.85, p < 0.01). 87.0% of eloquent tumors (Lacroix grade III) in the FGS group achieved GTR + NTR, compared to 52.2% of control group (OR 6.11, 95% CI 1.50-22.78, p < 0.05). For deep-seated tumors, the rate of GTR + NTR in the two groups were 91.7% and 53.3%, respectively (OR 9.62, 95% CI 1.05-116.50, p < 0.05). No significant difference of the preoperative NANO score of the two groups was found. The postoperative NANO score of the FGS group was significantly lower than the non-FGS group (2.56 ± 1.29 vs. 3.43 ± 1.63, p < 0.05). Median OS of the FGS group was 4.2 months longer than the non-FGS group despite no statistical difference (18.2 months vs. 14.0 months, HR 0.63, 95% CI 0.36-1.11, p = 0.112), while PSF was found significantly longer in FGS patients than those of the non-FGS group (11.2 months vs. 7.7 months, HR 0.59, 95% CI 0.35-0.99, p < 0.05).
CONCLUSIONS: Sodium fluorescein-guided surgery for high-grade gliomas in eloquent and deep-seated brain regions enables more extensive resection while preserving neurologic function and improve patient survival.

Fluorescence induced by the excitation of a fluorophore with plane-polarized light has a different polarization depending on the size of the fluorophore-containing reagent and the rate of its rotation. Based on this effect, many analytical systems have been implemented in which an analyte contained in a sample and labeled with a fluorophore (usually fluorescein) competes to bind to antibodies. Replacing antibodies in such assays with aptamers, low-cost and stable oligonucleotide receptors, is complicated because binding a fluorophore to them causes a less significant change in the polarization of emissions. This work proposes and characterizes the compounds of the reaction medium that improve analyte binding and reduce the mobility of the aptamer-fluorophore complex, providing a higher analytical signal and a lower detection limit. This study was conducted on aflatoxin B1 (AFB1), a ubiquitous toxicant contaminating foods of plant origins. Eight aptamers specific to AFB1 with the same binding site and different regions stabilizing their structures were compared for affinity, based on which the aptamer with 38 nucleotides in length was selected. The polymers that interact reversibly with oligonucleotides, such as poly-L-lysine and polyethylene glycol, were tested. It was found that they provide the desired reduction in the depolarization of emitted light as well as high concentrations of magnesium cations. In the selected optimal medium, AFB1 detection reached a limit of 1 ng/mL, which was 12 times lower than in the tris buffer commonly used for anti-AFB1 aptamers. The assay time was 30 min. This method is suitable for controlling almond samples according to the maximum permissible levels of their contamination by AFB1. The proposed approach could be applied to improve other aptamer-based analytical systems.

Analysis of exosomes provides important information for rapid and non-invasive screening of tumors. However, sensitive and convenient detection of exosomes remains technically challenging to date. Herein, a colorimetric aptasensor based on the light-stimulated oxidase-mimicking activity of FITC was constructed for detecting ovarian cancer (OC) exosomes. The aptasensor contained an EpCAM aptamer to capture OC exosomes. Cholesterol and fluorescein (FITC) were used to modify either end of the DNA (DNA anchor). The DNA anchor could combine with exosomes through a hydrophobic reaction between cholesterol and the lipid membrane. FITC oxidized 3,3\',5,5\'-tetramethylbenzidine (TMB) under a 365 nm LED light source in a temporally controllable manner under mild conditions, causing the solution to change from colorless to blue, and the corresponding UV-vis absorbance increased. Based on this principle, the exosomes were qualitatively analyzed by observing the color change with the naked eye. In parallel, the exosome concentration was also detected using UV-vis spectrophotometry. The linear range was from 2 × 105 to 100 × 105 particles per mL with a limit of detection of 1.77 × 105 particles per mL. The developed aptasensor also exhibited favorable selectivity and could discriminate the exosomes from OC cells and normal cells. Besides, the receiver operating characteristic (ROC) curve demonstrates that it is possible to distinguish between patients with OC and healthy donors (HDs) using exosomes as the biomarker. Our technology may expand the applications of DNA-based detection method-enabled OC diagnostic tools.

Amorphous silica particles (ASPs) have been reported to exhibit bioactive properties and are becoming the focus of attention as bioceramics. However, their interactions with proteins in living organisms remain to be understood and need to be investigated in order to achieve wider applications. Our research group found that chlorine (Cl)-containing ASPs are useful for protein immobilization. Photofunctional dyes (fluorescein (FS-), methylene blue (MB+)) that have the carboxy and amino groups as the main functional groups were immobilized on the Cl-containing ASPs via the mechanochemical method as the model molecule and their spectral properties were used to investigate and discuss the organic/inorganic interfacial bonding states. In FS-, the oxygen atoms of the carboxy groups in the molecule were immobilized by the hydrogen bonds with the silanol groups on the ASPs surfaces, indicating that there is an optimum Cl content for the immobilization as the monomer state. In the case of MB+, as the Cl concentration in the ASPs increases, the immobilization via the electrostatic interactions between the Cl in the ASPs and the terminal dimethylamino group, and the hydrogen bonding between the N atoms of the MB+ hetero ring and the particle silanol group were enhanced. These results mainly suggest that the protein adsorption system occurs through the hydrogen bonding between the carboxy groups of the protein and the silanol groups on the particles and via electrostatic interactions between the amino groups of the protein and the dissociated silanol groups and the contained Cl at the particles. Thus, the spectral characterization using dyes as probes is expected to predict the protein interactions with the amorphous silica particles.

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.