Dual inhibition of CPT1A and G6PD suppresses glioblastoma tumorspheres.

PURPOSE: Limited treatment options are currently available for glioblastoma (GBM), an extremely lethal type of brain cancer. For a variety of tumor types, bioenergetic deprivation through inhibition of cancer-specific metabolic pathways has proven to be an effective therapeutic strategy. Here, we evaluated the therapeutic effects and underlying mechanisms of dual inhibition of carnitine palmitoyltransferase 1A (CPT1A) and glucose-6-phosphate dehydrogenase (G6PD) critical for fatty acid oxidation (FAO) and the pentose phosphate pathway (PPP), respectively, against GBM tumorspheres (TSs). METHODS: Therapeutic efficacy against GBM TSs was determined by assessing cell viability, neurosphere formation, and 3D invasion. Liquid chromatography-mass spectrometry (LC-MS) and RNA sequencing were employed for metabolite and gene expression profiling, respectively. Anticancer efficacy in vivo was examined using an orthotopic xenograft model. RESULTS: CPT1A and G6PD were highly expressed in GBM tumor tissues. Notably, siRNA-mediated knockdown of both genes led to reduced viability, ATP levels, and expression of genes associated with stemness and invasiveness. Similar results were obtained upon combined treatment with etomoxir and dehydroepiandrosterone (DHEA). Transcriptome analyses further confirmed these results. Data from LC-MS analysis showed that this treatment regimen induced a considerable reduction in the levels of metabolites associated with the TCA cycle and PPP. Additionally, the combination of etomoxir and DHEA inhibited tumor growth and extended survival in orthotopic xenograft model mice. CONCLUSION: Our collective findings support the utility of dual suppression of CPT1A and G6PD with selective inhibitors, etomoxir and DHEA, as an efficacious therapeutic approach for GBM.

S-nitrosylated PARIS Leads to the Sequestration of PGC-1α into Insoluble Deposits in Parkinson's Disease Model.

Neuronal accumulation of parkin-interacting substrate (PARIS), a transcriptional repressor of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), has been observed in Parkinson's disease (PD). Herein, we showed that PARIS can be S-nitrosylated at cysteine 265 (C265), and S-nitrosylated PARIS (SNO-PARIS) translocates to the insoluble fraction, leading to the sequestration of PGC-1α into insoluble deposits. The mislocalization of PGC-1α in the insoluble fraction was observed in S-nitrosocysteine-treated PARIS knockout (KO) cells overexpressing PARIS WT but not S-nitrosylation deficient C265S mutant, indicating that insolubility of PGC-1α is SNO-PARIS-dependent. In the sporadic PD model, α-synuclein preformed fibrils (α-syn PFFs)-injected mice, we found an increase in PARIS, SNO-PARIS, and insoluble sequestration of PGC-1α in substantia nigra (SN), resulting in the reduction of mitochondrial DNA copy number and ATP concentration that were restored by N(ω)-nitro-L-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor. To assess the dopaminergic (DA) neuronal toxicity by SNO-PARIS, lentiviral PARIS WT, C265S, and S-nitrosylation mimic C265W was injected into the SN of either PBS- or α-syn PFFs-injected mice. PARIS WT and C265S caused DA neuronal death to a comparable extent, whereas C265W caused more severe DA neuronal loss in PBS-injected mice. Interestingly, there was synergistic DA loss in both lenti-PARIS WT and α-syn PFFs-injected mice, indicating that SNO-PARIS by α-syn PFFs contributes to the DA toxicity in vivo. Moreover, α-syn PFFs-mediated increment of PARIS, SNO-PARIS, DA toxicity, and behavioral deficits were completely nullified in neuronal NOS KO mice, suggesting that modulation of NO can be a therapeutic for α-syn PFFs-mediated neurodegeneration.

Arachnoid Remodeling by Clipping Technique Facilitates Surgical Maneuverability during Transsphenoidal Surgery for Pituitary Macroadenoma.

OBJECTIVE: Pituitary adenomas frequently extend into the suprasellar space. After a suprasellar tumor is removed, the superiorly extended arachnoid becomes redundant and sinks down into the intrasellar space which often hiders visualization and accessibility to the hidden space behind the evaginated arachnoid. We introduced arachnoid remodeling by clipping technique, and evaluated its usefulness and safety during TSS. METHODS: Total 223 patients who underwent arachnoid remodeling with our new clipping technique were included. Redundant arachnoid was clipped along the dural edge with multiple 2.6-mm titanium clips until the redundant arachnoid membrane no longer blocked the surgical route. To check for possible deterioration of hormonal function by this technique, we assessed anterior pituitary function of 166 patients who underwent arachnoid remodeling by clipping and compared this with those of other 429 control patients. RESULTS: Our technique greatly enhanced the accessibility and visualization of intrasellar and parasellar spaces, both of which are generally hindered by redundant arachnoid during transsphenoidal surgery (TSS). We found no difference in anterior pituitary function between a clip-assisted arachnoid remodeling group and the control group, implying that this technique does not result in hypopituitarism. CONCLUSION: During TSS for pituitary adenomas with suprasellar extension, arachnoid remodeling by clipping technique is very useful and convenient for the management of the redundant arachnoid membrane to enhance visualization and surgical accessibility.

Pedicled frontal periosteal rescue flap via eyebrow incision for skull base reconstruction (SevEN-002).

PURPOSE: Cerebrospinal fluid (CSF) leakage is one of the major complications after endoscopic endonasal surgery. The reconstructive nasoseptal flap is widely used to repair CSF leakage. However, it could not be utilized in all cases; thus, there was a need for an alternative. We developed a pericranial rescue flap that could cover both sellar and anterior skull base defects via the endonasal approach. A modified surgical technique that did not violate the frontal sinus and cause cosmetic problems was designed using the pericranial rescue flap. METHODS: We performed 12 cadaveric dissections to investigate the applicability of the lateral pericranial rescue flap. An incision was made, extending from the middle to the lateral part of the eyebrow. The pericranium layer was dissected away from the galea layer, from the supraorbital region towards the frontoparietal region. With endoscopic assistance, the periosteal flap was raised, the flap base was the pericranium layer at the eyebrow incision. After a burr-hole was made in the supraorbital bone, the pericranial flap was inserted via the intradural or extradural pathway. RESULTS: The mean size of the pericranial flap was 11.5 cm × 3.2 cm. It was large enough to cross the midline and cover the dural defects of the anterior skull base, including the sellar region. CONCLUSION: We demonstrated a modified endoscopic technique to repair the anterior skull base defects. This minimally invasive pericranial flap may resolve neurosurgical complications, such as CSF leakage.

Electrophysiological Monitoring of Neurochemical-Based Neural Signal Transmission in a Human Brain-Spinal Cord Assembloid.

Combining human brain organoids holds great potential in recapitulating the human brain's histological features and modeling neural disorders. However, current combined-brain organoid models focus on the internal interactions between different brain regions. In this study, we develop an engineered brain-spinal cord assembloid (eBSA) by coculturing cerebral organoids (COs) and motor neuron spheroids (MNSs). By connecting COs and MNSs, we generate a terminal for signal transfer from the brain to the whole body by mimicking the brain-spinal cord connection. After the formation of COs from human induced pluripotent stem cells and MNSs from human neural stem cells, MNSs are prepatterned into specific CO regions and assembled to form an eBSA. Caffeine serves as a neurochemical model to demonstrate neural signal transmission. When the MNSs in the eBSA contact the multielectrode array, the eBSA successfully shows an increased neural spiking speed on the motor neuron region by caffeine treatment, which means that neural stimulation signals transfer from the COs to MNSs. The neural stimulation effects of caffeine are tested on the MNSs only to prove the eBSA system's neural signal transmission, and there were no stimulus effects. Our results demonstrate that the eBSA system can monitor a caffeine-mediated excitatory signal as an output signal from the brain to the spinal cord. We believe that the eBSA system can be utilized as a screening platform to validate the stimulus signal transfer by neurochemicals. In addition, the accumulation of understanding of the neural signal transfer from CNS to PNS will provide better knowledge for controlling muscle actuators with the nervous system.

18F-FET PET/CT as a Diagnostic Tool for Brain Abscess.

ABSTRACT: A 49-year-old man presented with sudden right-sided weakness and seizure. Brain MRI identified a lobulated mass with diffusion restriction and irregular wall enhancement in the left parietal lobe. 18F-FET (O-(2-[18F]fluoroethyl)-l-tyrosine) PET/CT was performed, which identified a cystic mass in the left parietal lobe accompanied by FET uptake. Compartmentalized uptake was also confirmed throughout the left parietal lobe. Considering the relatively low target-to-background ratio and uptake observed in the entire left parietal lobe, the lesion was more likely to be a brain abscess than a tumor. The pathologic diagnosis after mass removal was acute and chronic inflammation with abscess.

α-Synuclein A53T Binds to Transcriptional Adapter 2-Alpha and Blocks Histone H3 Acetylation.

α-Synuclein (α-syn) is a hallmark amyloidogenic protein component of Lewy bodies in dopaminergic neurons affected by Parkinson's disease (PD). Despite the multi-faceted gene regulation of α-syn in the nucleus, the mechanism underlying α-syn crosstalk in chromatin remodeling in PD pathogenesis remains elusive. Here, we identified transcriptional adapter 2-alpha (TADA2a) as a novel binding partner of α-syn using the BioID system. TADA2a is a component of the p300/CBP-associated factor and is related to histone H3/H4 acetylation. We found that α-syn A53T was more preferentially localized in the nucleus than the α-syn wild-type (WT), leading to a stronger disturbance of TADA2a. Indeed, α-syn A53T significantly reduced the level of histone H3 acetylation in SH-SY5Y cells; its reduction was also evident in the striatum (STR) and substantia nigra (SN) of mice that were stereotaxically injected with α-syn preformed fibrils (PFFs). Interestingly, α-syn PFF injection resulted in a decrease in TADA2a in the STR and SN of α-syn PFF-injected mice. Furthermore, the levels of TADA2a and acetylated histone H3 were significantly decreased in the SN of patients with PD. Therefore, histone modification through α-syn A53T-TADA2a interaction may be associated with α-syn-mediated neurotoxicity in PD pathology.

ZNF746/PARIS promotes the occurrence of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer to cause liver cancer related deaths worldwide. Zinc finger protein 746 (ZNF746), initially identified as a Parkin-interacting substrate (PARIS), acts as a transcriptional repressor of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in Parkinson's disease. As recent studies reported that PARIS is associated with cancer onset, we investigated whether PARIS is associated with HCC. We found an increase in insoluble parkin and PARIS accumulation in the liver of diethylnitrosamine (DEN)-injected mice, leading to the downregulation of PGC-1α and nuclear respiratory factor 1 (NRF1). Interestingly, the occurrence of DEN-induced tumors was significantly alleviated in the livers of DEN-injected PARIS knockout mice compared to DEN-injected wild-type mice, suggesting that PARIS is involved in DEN-induced hepatocellular tumorigenesis. Moreover, H2O2-treated Chang liver cells showed accumulation of PARIS and downregulation of PGC-1α and NRF1. Thus, these results suggest that PARIS upregulation by oncogenic stresses can promote cancer progression by suppressing the transcriptional level of PGC-1α, and the modulation of PARIS can be a promising therapeutic target for HCC.

Angioleiomyoma in the Orbital Apex: A Case Report.

A 56-year woman presented eyeball pain and blurred vision. MRI revealed a small well-delineated solid tumor in the apex of right orbit with optic nerve compression. Intraoperatively, the tumor was found very fibrous, hypervascular and adhesive to surrounding structures. The tumor was completely removed with the combination of endoscopic and microscopic technique. Patient experienced transient oculomotor nerve palsy, which completely recovered 3 months after surgery. Herein we report a rare case of angioleiomyoma in the orbital apex.

Label-free detection of γ-aminobutyric acid based on silicon nanowire biosensor.

γ-Aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the central nervous system (CNS), which acts as a major biomarker for neurological disorders such as Parkinson's disease and Meningitis. To this end, the precise measurement of GABA molecule arisen as an important subject for the effective diagnosis and treatment of neurological disorders. However, yet highly sensitive biosensor systems which can analyze a wide range of GABA molecule in a fast response manner have not been reported. In this study, for the first time, a silicon nanowire field-effect transistor (FET) device based immunosensor was developed to detect GABA molecule. Zig-zag shaped silicon nanowires has been fabricated by electron beam lithography and the electrical property p-type FET device was validated through semiconductor analyzer. The optimal immobilizing condition of antibody against GABA molecule was determined by the fluorescent signal measurement. Various concentrations of GABA ranging from 970 fM to 9.7 µM were sensitively measured by conductance change on silicon nanowire-based through the immunoreactions. Further, owing to the ease of miniaturization and label-free system, we believe that the suggested device system has a potential to be utilized for an implantable biosensor to detect neurotransmitter in the brain and can create new opportunities in the field of diagnosis and treatment of neurological disorders.

Anti-diabetic properties of different fractions of Korean red ginseng.

ETHNOPHARMACOLOGICAL RELEVANCE: Korean red ginseng (KRG) has been traditionally used to treat diabetes. Ginsenosides are considered as the major bioactive components mediating anti-diabetic effects of KRG. However, considering that ginsenosides account for only about 3-4% of ginsengs, other fractions of KRG may also carry potential anti-diabetic effects. There is no study reporting the differentiated effects of ginsenosides (Spn) and non-saponin fractions (NSpn) of KRG on glycemic control. AIM OF THE STUDY: We investigated the effects of KRG, Spn, and NSpn on the indications of glycemic control and sought to elucidate physiological factors contributing their effects. MATERIALS AND METHODS: Human T2DM mimicking Nagoya-Shibata-Yasuda (NSY/hos) mice were given KRG, Spn, or NSpn admixed in rodent diet at 200 mg/kg/day for 24 weeks. Glycemic and obesity indications, blood lipid profile, systematic and local oxidative stress markers in metabolically important organs, and systematic inflammatory markers were assessed. Molecular assessments associated with glycemic control in liver and skeletal muscle were further performed. RESULTS: KRG attenuated deterioration in glucose homeostasis as evidenced by significantly lower fasting blood glucose from 22nd week and AUC during GTT at the end of the experiment compare to control. Spn enhanced insulin secretion in response to glucose stimulation and reduced protein level of glycogen phosphorylase in liver. On the other hand, NSpn ameliorated oxidative stress and inflammation. Some beneficial effects of Spn and NSpn were reflected in KRG treated mice. KRG also attenuated the accumulation of malondialdehyde in skeletal muscle and, accordingly, enhanced insulin responsiveness compare to control. CONCLUSION: Anti-diabetic properties of KRG are not solely determined by the contents of ginsenosides but the harmonic functions of its different fractions.

Electrical Property of Graphene and Its Application to Electrochemical Biosensing.

Graphene, a single atom thick layer of two-dimensional closely packed honeycomb carbon lattice, and its derivatives have attracted much attention in the field of biomedical, due to its unique physicochemical properties. The valuable physicochemical properties, such as high surface area, excellent electrical conductivity, remarkable biocompatibility and ease of surface functionalization have shown great potentials in the applications of graphene-based bioelectronics devices, including electrochemical biosensors for biomarker analysis. In this review, we will provide a selective overview of recent advances on synthesis methods of graphene and its derivatives, as well as its application to electrochemical biosensor development. We believe the topics discussed here are useful, and able to provide a guideline in the development of novel graphene and on graphene-like 2-dimensional (2D) materials based biosensors in the future.

Molecular mechanisms of biogenesis of apoptotic exosome-like vesicles and their roles as damage-associated molecular patterns.

Recent research has led to contradictory notions regarding the conventional theory that apoptotic cell death can evoke inflammatory or immunogenic responses orchestrated by released damage-associated patterns (DAMPs). By inducing IL-1ß from bone marrow-derived macrophages in an effort to determine the inflammatory mediators released from apoptotic cells, we found that exosomal fractions called "apoptotic exosome-like vesicles" (AEVs) prepared from apoptotic-conditioned medium were the main inflammatory factors. These AEVs showed characteristics of exosomes in their size, density, morphology, and protein expression but had unique marker proteins, sphingosine-1-phosphate receptors 1 and 3 (S1PR1 and 3). Their biogenesis was completely dependent on cellular sphingosine-1-phosphate (S1P)/S1PRs signaling from multiple fine spindles of plasma membrane accompanied by F-actin, S1PR1, S1PR3, and CD63 at the early apoptotic phase and progressing to the maturation of F-actin-guided multivesicular endosomes mediated by Gßγ subunits of S1PRs downstream. S1P-loaded S1PRs on AEVs were critical factors for inducing IL-1ß via NF-κB transcriptional factor and p38 MAPK, possibly through the RHOA/NOD2 axis, in differentiating macrophages. The AEVs induced genes of proinflammatory cytokines, chemokines, and mediators in both in vitro and in vivo models. In conclusion, AEVs could be key inflammatory mediators, acting as DAMPs that could explain the pathogeneses of various chronic inflammations, autoimmune diseases, or cancers in the future.

Bifunctional Au@Bi2 Se3 Core-Shell Nanoparticle for Synergetic Therapy by SERS-Traceable AntagomiR Delivery and Photothermal Treatment.

For the first time, topological insulator bismuth selenide nanoparticles (Bi2 Se3 NP) are core-shelled with gold (Au@Bi2 Se3 ) i) to represent considerably small-sized (11 nm) plasmonic nanoparticles, enabling accurate bioimaging in the near-infrared region; ii) to substantially improve Bi2 Se3 biocompatibility, iii) water dispersibility, and iv) surface functionalization capability through straightforward gold-thiol interaction. The Au@Bi2 Se3 is subsequently functionalized for v) effective targeting of SH-SY5Y cancer cells, vi) disrupting the endosome/lysosome membrane, vii) traceable delivery of antagomiR-152 and further synergetic oncomiR knockdown and photothermal therapy (PTT). Unprecedentedly, it is observed that the Au shell thickness has a significant impact on evoking the exotic plasmonic features of Bi2 Se3 . The Au@Bi2 Se3 possesses a high photothermal conversion efficiency (35.5%) and a remarkable surface plasmonic effect (both properties are approximately twofold higher than those of 50 nm Au nanoparticles). In contrast to the siRNA/miRNA delivery methods, the antagomiR delivery is based on strand displacement, in which the antagomiR-152 is displaced by oncomiR-152 followed by a surface-enhanced Raman spectroscopy signal drop. This enables both cancer cell diagnosis and in vitro real-time monitoring of the antagomiR release. This selective PTT nanoparticle can also efficiently target solid tumors and undergo in vivo PTT, indicating its potential clinical applications.

Vestibular schwannoma atypically invading temporal bone.

Vestibular schwannoma (VS) usually present the widening of internal auditory canal (IAC), and these bony changes are typically limited to IAC, not extend to temporal bone. Temporal bone invasion by VS is extremely rare. We report 51-year-old man who revealed temporal bone destruction beyond IAC by unilateral VS. The bony destruction extended anteriorly to the carotid canal and inferiorly to the jugular foramen. On histopathologic examination, the tumor showed typical benign schwannoma and did not show any unusual vascularity or malignant feature. Facial nerve was severely compressed and distorted by tumor, which unevenly eroded temporal bone in surgical field. Vestibular schwannoma with atypical invasion of temporal bone can be successfully treated with combined translabyrinthine and lateral suboccipiral approach without facial nerve dysfunction. Early detection and careful dissection of facial nerve with intraoperative monitoring should be considered during operation due to severe adhesion and distortion of facial nerve by tumor and eroded temporal bone.

Granular cell tumor in the pituitary stalk: a case report.

Granular cell tumors (GCTs) have been reported in various tissues, especially the skin and subcutaneous soft tissue of the head and neck. We report a 60-year-old man who presented with intermittent headache and dizziness for 3 months, but no other neurological symptoms. Magnetic resonance imaging (MRI) showed the presence of a mass in the pituitary stalk, and contrast-enhanced MRI showed nodular enhancement in this region. The lesion was completely excised microscopically via a frontotemporal (pterional) approach. On pathological examination, a final diagnosis of a typical GCT was made.

Association of nasal inflammation and lower airway responsiveness in schoolchildren based on an epidemiological survey.

BACKGROUND/AIMS: We sought to increase our understanding of the rhinitis-asthma relationship and improve strategies for the treatment of patients with these diseases. The aim of this study was to identify a connection between upper airway inflammation and lower airway responsiveness. METHODS: We counted eosinophils on nasal smears, and performed spirometry, allergic skin tests, and methacholine challenge tests in 308 schoolchildren plus a questionnaire on respiratory symptoms. The methacholine concentration causing a 20% fall in forced expiratory volume in 1 second (PC20 < 25 mg/mL) was used as the threshold of bronchial hyperresponsiveness (BHR). RESULTS: In total, 26% of subjects had positive nasal eosinophils on a smear, and 46.2% of subjects had BHR at < 25 mg/mL methacholine PC20. Nasal symptoms were higher in subjects with than without nasal eosinophils (p = 0.012). Asthma symptoms did not differ between subjects with and without nasal eosinophils. Nasal eosinophils were higher in subjects with atopy than those without (p = 0.006), and there was no difference in PC20 methacholine according to atopy (15.5 ± 1.07 vs. 17.5 ± 0.62; p > 0.05). No difference in BHR was detected when comparing subjects with and without nasal eosinophils. There were significant differences in the PC20 between subjects with greater than 50% nasal eosinophils and without nasal eosinophils (11.01 ± 2.92 mg/mL vs. 17.38 ± 0.61 mg/mL; p < 0.001). CONCLUSIONS: These findings demonstrated that nasal eosinophilic inflammation might contribute to lower airway responsiveness in schoolchildren, based on an epidemiological survey.

Construction of an infectious cDNA clone of genotype 1 avian hepatitis E virus: characterization of its pathogenicity in broiler breeders and demonstration of its utility in studying the role of the hypervariable region in virus replication.

A full-length infectious cDNA clone of the genotype 1 Korean avian hepatitis E virus (avian HEV) (pT11-aHEV-K) was constructed and its infectivity and pathogenicity were investigated in leghorn male hepatoma (LMH) chicken cells and broiler breeders. We demonstrated that capped RNA transcripts from the pT11-aHEV-K clone were translation competent when transfected into LMH cells and infectious when injected intrahepatically into the livers of chickens. Gross and microscopic pathological lesions underpinned the avian HEV infection and helped characterize its pathogenicity in broiler breeder chickens. The avian HEV genome contains a hypervariable region (HVR) in ORF1. To demonstrate the utility of the avian HEV infectious clone, several mutants with various deletions in and beyond the known HVR were derived from the pT11-aHEV-K clone. The HVR-deletion mutants were replication competent in LMH cells, although the deletion mutants extending beyond the known HVR were non-viable. By using the pT11-aHEV-K infectious clone as the backbone, an avian HEV luciferase reporter replicon and HVR-deletion mutant replicons were also generated. The luciferase assay results of the reporter replicon and its mutants support the data obtained from the infectious clone and its derived mutants. To further determine the effect of HVR deletion on virus replication, the capped RNA transcripts from the wild-type pT11-aHEV-K clone and its mutants were injected intrahepatically into chickens. The HVR-deletion mutants that were translation competent in LMH cells displayed in chickens an attenuation phenotype of avian HEV infectivity, suggesting that the avian HEV HVR is important in modulating the virus infectivity and pathogenicity.

Changes in biomechanical properties of the cornea and intraocular pressure after myopic laser in situ keratomileusis using a femtosecond laser for flap creation determined using ocular response analyzer and Goldmann applanation tonometry.

PURPOSE: To compare intraocular pressure (IOP) measurements before and after laser in situ keratomileusis (LASIK) using a femtosecond laser for flap creation, and to identify factors that may influence the preoperative and postoperative IOP, and the change in IOP after LASIK. METHODS: Forty eyes from 20 patients who underwent treatment for myopia using a femtosecond laser for flap creation were enrolled in this study. The IOP and corneal biomechanical markers were prospectively measured preoperatively and 1 month after LASIK with Goldmann applanation tonometry (GAT) and the ocular response analyzer (ORA). Manifest refraction spherical equivalent, central corneal thickness, ablation depth, and mean corneal curvature (K reading) were also recorded. RESULTS: After LASIK, there was a significant reduction in the IOP measurement with respect to the corneal-compensated intraocular pressure (IOPcc) (Δ=-0.67±2.07 mm Hg), Goldmann-correlated pressure (IOPg) (Δ=-3.92±2.19 mm Hg), and GAT (Δ=-2.6±2.51). Multiple regression analysis revealed that the corneal hysteresis (CH) and corneal resistance factor (CRF) are statistically significant predictors of IOPcc, IOPg, and GAT (P<0.000). In this analysis, the preoperative manifest refraction spherical equivalent, CH, and CRF were significant predictors of ΔIOPcc (adjusted R²=0.401) and ΔIOPg (adjusted R²=0.386). The preoperative SE and central corneal thickness significantly predicted ΔGAT (adjusted R²=0.464). CONCLUSIONS: ORA provides a more complete measurement of IOP after LASIK with a femtosecond laser than GAT because ORA provides greater knowledge of the corneal biomechanics in terms of CH and CRF.

Long-term outcomes of cytomegalovirus reactivation in patients with moderate to severe ulcerative colitis: a multicenter study.

BACKGROUND/AIMS: Cytomegalovirus (CMV) reactivations are frequently observed in patients with active ulcerative colitis (UC), and ganciclovir therapy is effective in patients with steroid-refractory UC. This study aimed to determine the long-term outcomes of CMV reactivation and the long-term therapeutic efficacy of ganciclovir treatment. METHODS: This retrospective multicenter study included a cohort of 72 patients with moderate-to-severe UC who were evaluated for CMV reactivation at the time of their initial UC flare. Colectomy, disease relapse, and the recurrence rate of CMV reactivation were investigated. RESULTS: The mean duration of follow-up for the 72 patients was 43.16±19.78 months (range, 1 to 67 months). The cumulative colectomy (log-rank, p=0.025) and disease flare-up rates (log-rank, p=0.048) were significantly higher in the CMV-positive group. Of the 11 patients who were successfully treated with ganciclovir in the initial treatment, three patients (27.3%) experienced CMV reactivation, and six patients (54.5%) experienced poor outcomes, such as the need for colectomy or a steroid-dependent state. CONCLUSIONS: The patients who had CMV-reactivated UC showed poor outcomes at the long-term follow-up, and the long-term efficacy of ganciclovir therapy was marginal. Careful assessment is necessary for patients who exhibit evidence of CMV reactivation.