Cranial Nerve Palsy and Risk of Kidney Cancer: A Nationwide Population-Based Study.

Background and Objective: Understanding whether cranial nerve palsy (CNP) acts as an independent risk factor for kidney cancer could have important implications for patient care, early detection, and potentially the development of preventive strategies for this type of cancer in individuals with CNP. This study aimed to examine the risk of kidney cancer following the onset of ocular motor CNP and assess whether CNP could be considered an independent risk factor for kidney cancer. Materials and Methods: A population-based cohort study was conducted using data from the National Sample Cohort (NSC) database of Korea's National Health Insurance Service which was collected from 2010 to 2017. Follow-up was until kidney cancer development, death, or 31 December 2018. Cox proportional hazard regression analysis was performed to determine hazard ratios (HRs) for kidney cancer according to CNP status. Participants aged 20 years or more diagnosed with CNP from 2010 to 2017 were included. Exclusions comprised individuals with specific pre-existing conditions, inability to match a control group, and missing data, among others. CNP patients were age-sex matched in a 1:5 ratio with control cases. The primary outcome was incidence of kidney cancer during the follow-up period. Results: This study comprised 118,686 participants: 19,781 in the CNP group, and 98,905 in the control group. Compared to the control group, participants with CNP had a higher risk of kidney cancer (adjusted HR in model 4, 1.599 [95% CI, 1.116-2.29]). After a 3-year lag period, the CNP group had a significantly higher risk (adjusted HR in model 4, 1.987 [95% CI, 1.252-3.154]). Conclusions: Ocular motor CNP may be an independent risk factor for kidney cancer, as indicated by a higher incidence of kidney cancer in CNP patients. Further research is needed to elucidate the underlying mechanisms and explore potential preventive measures for kidney cancer in patients with ocular motor CNP.

Ocular Motor Cranial Nerve Palsies and Increased Risk of Primary Malignant Brain Tumors: South Korean National Health Insurance Data.

The aim of this study was to investigate the association between ocular motor cranial nerve palsies (OMCNP) and the occurrence of primary malignant brain tumors in a Korean population, using the national sample cohort database from Korea National Health Insurance Service (KNHIS). KNHIS data between 2010 and 2017 were analyzed. Our sample encompassed 118,686 participants, including 19,781 from a recently diagnosed OMCNP cohort and 98,905 from a matched control cohort through a 1:5 propensity score matching based on age and gender. To counteract the issue of reverse causation, we integrated a one-year time lag in our sensitivity analysis. Study participants were followed up until 31 December 2019. Cox proportional hazard regression analysis was used to compute the adjusted hazard ratio (HR) for primary malignant brain tumors according to the OMCNP diagnosis. Additionally, we performed a subgroup analysis to discern effects of various factors on the association between OMCNP and primary malignant brain tumors. HR for primary malignant brain tumors was 3.272 (95% confidence interval [CI]: 2.294 to 4.665) in the OMCNP cohort compared to the control cohort in a fully adjusted model for age, sex, socio-economic status, smoking, drinking, regular physical exercise, hypertension, diabetes, dyslipidemia, obesity, chronic kidney disease, and human immunodeficiency virus infection. Further subgroup analysis revealed that the risk of primary malignant brain tumors was significantly increased in women with OMCNP compared to men with OMCNP (HR: 5.118 in women vs. 2.441 in men, p = 0.0440), and in those aged <65 years than in those aged ≥65 years (HR: 6.951 in age < 65 years vs. 1.899 in age ≥ 65 years, p = 0.0006). Our population-based cohort study demonstrated a significantly increased risk of subsequent primary malignant brain tumors in patients with OMCNP. Particularly, OMCNP-afflicted women aged below 65 manifested a heightened probability of developing primary malignant brain tumors compared to those devoid of OMCNP.

Dynamic Changes in Metabolic Status Are Associated With Risk of Ocular Motor Cranial Nerve Palsies.

BACKGROUND: To investigate whether recovery from or development of metabolic syndrome (MetS) in a population is associated with an altered risk for ocular motor cranial nerve palsy (CNP). METHODS: This cohort study included 4,233,273 adults without a history of ocular motor cranial nerve palsy (ocular motor CNP) who underwent 2 consecutive biennial health screenings provided by the Korean National Health Insurance System between 2009 and 2011. They were followed up until December 31, 2018. Participants were categorized into a MetS-free, MetS-developed, MetS-recovered, or MetS-chronic group. A multivariable Cox proportional hazard regression model was used. Model 3 was adjusted for age, sex, smoking status, alcohol consumption, and physical activity. RESULTS: Compared with the MetS-free group, the MetS-chronic group had the highest risk of ocular motor CNP (hazard ratio [HR]: 1.424; 95% confidential interval [CI]: 1.294-1.567, Model 3), followed by the MetS-developed group (HR: 1.198, 95% CI: 1.069-1.343), and the MetS-recovered group (HR: 1.168, 95% CI: 1.026-1.311) after adjusting for potential confounders. The hazard ratio of ocular motor CNP in men with chronic MetS was 1.566 (95% CI, 1.394-1.761) while that of women with chronic MetS was 1.191 (95% CI, 1.005-1.411). Among age groups, those in their 30s and 40s showed the highest association between dynamic MetS status and ocular motor CNP. CONCLUSIONS: In our study, recovering from MetS was associated with a reduced risk of ocular motor CNP compared with chronic MetS, suggesting that ocular motor CNP risk could be managed by changing MetS status.

Ocular motility disorders following coronavirus disease-19 vaccination.

PURPOSE: To describe clinical manifestations and short-term prognosis of ocular motility disorders following coronavirus disease-2019 (COVID-19) vaccination. METHODS: Ocular motility disorders were diagnosed by clinical assessment, high-resolution magnetic resonance imaging, and laboratory testing. Clinical manifestations, short-term prognosis, and rate of complete recovery were analyzed. RESULTS: Sixty-three patients (37 males, 26 females) with a mean age of 61.6 ± 13.3 years (range, 22-81 years) were included in this study. Among 61 applicable patients with sufficient information regarding medical histories, 38 (62.3%) had one or more significant underlying past medical histories including vasculopathic risk factors. The interval between initial symptoms and vaccination was 8.6 ± 8.2 (range, 0-28) days. Forty-two (66.7%), 14 (22.2%), and 7 (11.1%) patients developed symptoms after the first, second, and third vaccinations, respectively. One case of internuclear ophthalmoplegia, 52 cases of cranial nerve palsy, two cases of myasthenia gravis, six cases of orbital diseases (such as myositis, thyroid eye disease, and IgG-related orbital myopathy), and two cases of comitant vertical strabismus with acute onset diplopia were found. Among 42 patients with follow-up data (duration: 62.1 ± 40.3 days), complete improvement, partial improvement, no improvement, and exacerbation were shown in 20, 15, 3, and 4 patients, respectively. CONCLUSION: This study provided various clinical features of ocular motility disorders following COVID-19 vaccination. The majority of cases had a mild clinical course while some cases showed a progressive nature. Close follow-up and further studies are needed to elucidate the underlying mechanisms and long-term prognosis.

Predicting visual outcomes after decompression of pituitary tumours based on stratified inner-retinal layer thickness and age.

PURPOSE: The purpose of the study was to evaluate the potential role of stratified preoperative optical coherence tomography (OCT) measurements and age in predicting postoperative visual field (VF) improvement among adult patients with chiasmal compression due to pituitary tumours after decompression surgery. METHODS: Postoperative visual outcomes were analysed using mean deviation of the VF test. Eyes were divided into three groups based on preoperative OCT parameters including peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness: groups 1, 2 and 3 with pRNFL thickness <65 µm, 65 µm or more but <85 µm, and 85 µm or more, respectively. The GCIPL thickness was also divided into three groups based on values ranging from 55 to 77 µm. Each group was further categorized according to age: 20 years or older but younger than 40 years, 40 years or older but younger than 60, and 60 years or older. RESULTS: This study included 197 eyes of 197 patients with chiasmal compression due to pituitary tumours. No patient showed complete VF recovery in group 1 with a preoperative pRNFL thickness <65 µm or a GCIPL thickness <55 µm regardless of age. These groups showed the worst VF outcome (pRNFL, p = 0.0001; GCIPL, p < 0.0001). However, a significant recovery in VF (greater than 2 dB) was observed in 45% of group 1 patients based on pRNFL thickness and in 61.54% of group 1 patients according to GCIPL thickness. In groups 2 and 3 with a preoperative pRNFL thickness of 65 µm or more and a GCIPL thickness of 55 µm or more, the rate of complete VF recovery decreased as subjects' ages increased. Group 3 with a preoperative pRNFL thickness of 85 µm or more and a GCIPL thickness of 77 µm or more were 2.5-fold and 4.0-fold more likely to completely recover VF, respectively, compared with group 2. CONCLUSIONS: Stratified preoperative pRNFL and GCIPL thicknesses measured via OCT in different age categories are effective biomarkers for predicting visual functional outcomes.

Ganglion cell inner plexiform layer thickness measured by optical coherence tomography to predict visual outcome in chiasmal compression.

We evaluated the prognostic value of the preoperative macular ganglion cell inner plexiform layer (mGCIPL) thickness along with peripapillary retinal nerve fiber layer (pRNFL) thickness measured by optical coherence tomography (OCT) and estimated an optimal cut-off value to predict postoperative visual field (VF) recovery in adult patients with chiasmal compression after decompression surgery. Two hundred forty eyes of 240 patients aged 20 years or older for which preoperative high-definition Cirrus OCT parameters and pre- and postoperative visual function data were available. The prognostic power of pRNFL and mGCIPL thicknesses for complete postoperative VF recovery or significant VF improvement (improvement ≥ 2 dB in the mean deviation) were assessed. The cut-off values for OCT parameters for VF recovery were estimated. The study found that the higher the preoperative pRNFL and mGCIPL thicknesses, the higher the probability of complete postoperative VF recovery (p = 0.0378 and p = 0.0051, respectively) or significant VF improvement (p = 0.0436 and p = 0.0177, respectively). The area under the receiver operating characteristic analysis of preoperative OCT parameters demonstrated that the mGCIPL thickness showed an area under the curve (AUC) of more than 0.7 for complete VF recovery after decompression surgery (AUC = 0.725, 95% CI: 0.655, 0.795), and the optimal mGCIPL thickness cut-off value for complete VF recovery was 77.25 µm (sensitivity 69% and specificity 69%). Preoperative mGCIPL thickness was a powerful predictor of visual functional outcome after decompression surgery for chiasmal compression.

Parafoveal and peripapillary vessel density in pediatric and juvenile craniopharyngioma patients.

We assessed the retinal microvascular alterations detected by optical coherence tomography angiography (OCT-A) in pediatric and juvenile craniopharyngioma (CP) patients with chiasmal compression. We included 15 eyes of 15 pediatric or juvenile CP patients and 18 eyes of 18 healthy subjects. The evaluation of vessel density from the superficial retinal capillary plexus (SRCP), the deep retinal capillary plexus, and the radial peripapillary capillary (RPC) segments was obtained by OCT-A. The association between vessel density measures and functional and structural measurements was also analyzed. There were significant reductions in the nasal sector of the SRCP (p < 0.0001) and all sectors of the RPC segment vessel density (nasal, temporal, and superior; p < 0.0001, inferior; p = 0.0015) in CP patients postoperatively compared to the healthy subjects. The peripapillary retinal nerve fiber layer (r = 0.6602, p = 0.0074) and ganglion cell-inner plexiform layer thicknesses (r = 0.7532, p = 0.0030) were associated with RPC segment vessel density. Visual acuity (r = - 0.5517, p = 0.0330) and temporal visual field sensitivity loss (r = 0.5394, p = 0.0465) showed an association with SRCP vessel density. In pediatric and juvenile patients with CP, parafoveal and peripapillary vascular changes following chiasmal compression were observed. The changes in vascular structures were closely related to structural and functional outcomes.

Factors affecting the health-promoting behavior of thyroid cancer survivors: comparison by stage of cancer survivorship.

PURPOSE: The purpose of this study was to identify differences in factors affecting health-promoting behaviors according to the survival stage of thyroid cancer survivors. METHODS: This descriptive cross-sectional study analyzed data from 354 thyroid cancer survivors after diagnosis. The survivors were divided into three stages: (1) the acute stage (< 2 years after diagnosis), (2) extended stage (2-5 years after diagnosis), and (3) permanent stage (≥ 5 years after diagnosis). To measure health-promoting behavior, the revised Korean version of the Health Promoting Lifestyle Profile questionnaires was used. The factors affecting the health-promoting behavior included social support, self-efficacy, fear of recurrence, and symptoms. Multiple regression analysis was used to analyze factors affecting the health-promoting behavior according to survival stage. RESULT: The factors affecting the health-promoting behavior of thyroid cancer survivors differed by survival stage. In the acute stage, the factors of health-promoting behavior were self-efficacy (t = 4.76, p < .001) and social support (t = 3.54, p < .001). In the extended stage, symptoms (t = - 3.65, p < .001), social support (t = 2.61, p = .011), fear of recurrence (t = 2.18, p = .032), and receipt of radioiodine treatment (t = - 2.18, p = .032) were found to be significant variables that affected health-promoting behaviors. In the permanent stage, social support (t = 2.79, p = .007), receipt of radioiodine treatment (t = - 3.21, p = .002), and age (t = - 2.77, p = .007) were significant variables that affected health-promoting behaviors. CONCLUSION: The experience of thyroid cancer survivors varies as they progress through the survival stages; thus, health-promotion interventions should be tailored to each survival stage.

Association of Obesity and Incidence of Third, Fourth, and Sixth Cranial Nerve Palsies.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess the association between obesity and the development of third, fourth, and sixth cranial nerve palsy (CNP). METHODS: We analyzed a cohort of 4,067,842 adults aged between 20 and 90 years who underwent health checkups within the National Health Insurance Service between January 1 and December 31, 2009. The participants were followed until December 31, 2017. Cox proportional hazards regression analysis was used to determine the adjusted hazard ratios (HRs) for CNP. Model 3 (the main analysis model) was adjusted for age, sex, smoking status, alcohol consumption, and physical activity. Model 4 was additionally adjusted for hypertension, dyslipidemia, and diabetes mellitus in the setting of model 3. RESULTS: A total of 5,835 individuals were diagnosed with CNP during the follow-up period (7.3 years). General obesity (body mass index [BMI] ≥25 kg/m2) was associated with an increased risk of CNP compared to individuals without general obesity (model 3, HR 1.248, 95% CI 1.184-1.315; model 4, HR 1.162, 95% CI 1.102-1.227). Abdominal obesity (waist circumference [WC] ≥90 cm in men and ≥85 cm in women) also showed an increased HR compared to individuals without abdominal obesity (model 3, 1.239, 95% CI 1.170-1.313; model 4, HR 1.127, 95% CI 1.062-1.196). Compared to the group without either type of obesity, the group with only abdominal obesity (model 3, HR 1.167, 95% CI 1.035-1.317), the group with only general obesity (HR 1.19, 95% CI 1.14-1.24), and the group with both obesity types (HR 1.317, 95% CI 1.236-1.404) showed increased HRs for CNP. CONCLUSION: Based on our population-based cohort study, both general and abdominal obesity increased the risk of CNP. Also, the combination of general and abdominal obesity may further increase the risk of CNP.

Association between metabolic syndrome and incidence of ocular motor nerve palsy.

To assess the association between metabolic syndrome (MetS) and the development of third, fourth, and sixth cranial nerve palsy (CNP). Health checkup data of 4,067,842 individuals aged between 20 and 90 years provided by the National Health Insurance Service (NHIS) of South Korea between January 1, 2009, and December 31, 2009, were analyzed. Participants were followed up to December 31, 2017. Hazard ratio (HR) and 95% confidence interval (CI) of CNP were estimated using Cox proportional hazards regression analysis after adjusting for potential confounders. Model 1 included only incident CNP as a time-varying covariate. Model 2 included model 1 and individual's age and sex. Model 3 included model 2, smoking status, alcohol consumption, and physical activity of individuals. We identified 5,835 incident CNP cases during the follow-up period (8.22 ± 0.94 years). Individuals with MetS (n = 851,004) showed an increased risk of CNP compared to individuals without MetS (n = 3,216,838) after adjustment (model 3: HR = 1.35, 95% CI 1.273-1.434). CNP incidence was positively correlated with the number of MetS components (log-rank p < 0.0001). The HR of CNP for males with MetS compared to males without MetS was higher than that of females with MetS compared to females without MetS (HR: 1.407, 95% CI 1.31-1.51 in men and HR: 1.259, 95% CI 1.13-1.40 in women, p for interaction = 0.0017). Our population-based large-scale cohort study suggests that MetS and its components might be risk factors for CNP development.

Clinical predictors of cybersickness in virtual reality (VR) among highly stressed people.

The use of virtual reality (VR) in the treatment of psychiatric disorders is increasing, and cybersickness has emerged as an important obstacle to overcome. However, the clinical factors affecting cybersickness are still not well understood. In this study, we investigated clinical predictors and adaptation effect of cybersickness during VR application in highly stressed people. Eighty-three healthy adult participants with high stress level were recruited. At baseline, we conducted psychiatric, ophthalmologic, and otologic evaluations and extracted physiological parameters. We divided the participants into two groups according to the order of exposure to VR videos with different degrees of shaking and repetitively administered the Simulator Sickness Questionnaire (SSQ) and the Fast Motion sickness Scale (FMS). There was no significant difference in changes in the SSQ or the FMS between groups. The 40-59 years age group showed a greater increase in FMS compared to the 19-39 years age group. Smoking was negatively associated with cybersickness, and a high Positive Affect and Negative Affect Schedule score was positively associated with cybersickness. In conclusion, changing the intensity of shaking in VR did not affect cybersickness. While smoking was a protective factor, more expression of affect was a risk factor for cybersickness.

Inner and outer retinal layer thickness alterations in pediatric and juvenile craniopharyngioma.

We evaluated postoperative retinal thickness in pediatric and juvenile craniopharyngioma (CP) patients with chiasmal compression using optical coherence tomography (OCT) auto-segmentation. We included 18 eyes of 18 pediatric or juvenile patients with CP and 20 healthy controls. Each thickness of the macular retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor layer was compared between the CP patients and healthy controls. There was significant thinning in the macular RNFL (estimates [µm], superior, - 10.68; inferior, - 7.24; nasal, - 14.22), all quadrants of GCL (superior, - 16.53; inferior, - 14.37; nasal, - 24.34; temporal, - 9.91) and IPL (superior, - 11.45; inferior, - 9.76; nasal, - 15.25; temporal, - 4.97) in pediatric and juvenile CP patients postoperatively compared to healthy control eyes after adjusting for age and refractive errors. Thickness reduction in the average and nasal quadrant of RNFL, GCL, and IPL was associated with peripapillary RNFL thickness, and reduced nasal quadrant GCL and IPL thicknesses were associated with postoperative visual field defects. In pediatric and juvenile patients with CP, decreased inner retinal layer thickness following chiasmal compression was observed. The changes in retinal structures were closely related to peripapillary RNFL thinning and functional outcomes.

Changes in parafoveal and peripapillary perfusion after decompression surgery in chiasmal compression due to pituitary tumors.

We evaluated changes in parafoveal and peripapillary vessel density in chiasmal compression after decompression surgery using optical coherence tomography angiography (OCT-A). Sixty-two eyes with chiasmal compression for which preoperative and postoperative (4-6 months) OCT, OCT-A, visual field (VF), and comprehensive ophthalmic data were available, and 44 healthy eyes were evaluated. Vessel densities of the superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), and radial peripapillary capillary (RPC) segment were assessed using OCT-A. The postoperative measurements were compared with preoperative data. Preoperative peripapillary retinal nerve fiber layer, macular ganglion cell-inner plexiform layer thickness, and vessel densities of SRCP and RPC segments in patients' eyes were significantly reduced compared to those of healthy controls (P < 0.0001, P < 0.0001, P = 0.0052, and P = 0.0085, respectively). Vessel densities were significantly decreased in the SRCP (P < 0.0001), DRCP (P = 0.0017), and RPC segments (P < 0.0001) after surgery compared to the preoperative values. Significant associations between the postoperative SRCP and DRCP vessel density changes and preoperative SRCP (r = - 0.3195, P = 0.0114) and DRCP (r = - 0.5165, P < 0.0001) vessel densities were found, respectively. There were also significant associations between postoperative SRCP vessel density changes and VF changes (r = - 0.2586, P = 0.0424). These findings indicate that decreased perfusion around the optic nerve head and on the macula associated with chiasmal compression could further progress after decompression surgery. Further functional and longer-term clinical studies are needed to elucidate the clinical implications of these findings.

Longitudinal Changes in the Retinal Microstructures of Eyes With Chiasmal Compression.

OBJECTIVE: To test the hypothesis that there was a temporal change in the retinal microstructure after decompression surgery for chiasmal compression, the 1-year longitudinal changes in the inner and outer retinal thickness after decompression surgery were analyzed using spectral-domain optical coherence tomography (SD-OCT) with linear mixed-effects models. METHODS: SD-OCT was obtained from 87 eyes with chiasmal compression and compared to 100 healthy controls. The preoperative and 1-year postoperative longitudinal changes in the retinal layer thickness were measured. The thickness of each of the following retinal layers was analyzed: the macular retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), the inner plexiform layer (IPL), the inner nuclear layer, the outer plexiform layer, the outer nuclear layer, and the photoreceptor layer. RESULTS: The RNFL, GCL, and IPL showed thinning at a rate of 1.068 µm/y (95% confidence interval [CI], 0.523, 1.613), 1.189 µm/y (95% CI 0.452, 1.925), and 1.177 µm/y (95% CI 0.645, 1.709), respectively, after decompression surgery. The preoperative thickness of the intraretinal layer was associated with postoperative visual field recovery (RNFL, odds ratio [OR] 1.221, 95% CI 1.058, 1.410; GCL, OR 1.133, 95% CI 1.024, 1.254; and IPL, OR 1.174, 95% CI 1.002, 1.376). CONCLUSIONS: The changes in retinal microstructure persisted and progressed in eyes with chiasmal compression after decompression surgery. The findings provide insight into the biological and anatomical sequelae following chiasmal compression. The preoperative thickness of the inner retinal layers was associated with postoperative visual field recovery.

Correction: Factors affecting online health community participation behavior in patients with thyroid cancer.

[This corrects the article DOI: 10.1371/journal.pone.0235056.].

Factors affecting online health community participation behavior in patients with thyroid cancer.

Globally, cancer patients obtain much of their disease information online. Online health communities allow patients to share questions and information about diseases. However, there have been few studies on the factors affecting online health community participation behavior in cancer patients. Online social networking is associated with mental health problems, and patients with thyroid cancer experience high levels of distress, anxiety and depression. The purpose of this study was to investigate factors associated with use of online health communities by patients with thyroid cancer to understand the characteristics of patients participating in such online communities. A questionnaire survey was completed by 114 thyroid cancer patients admitted for surgery at a general hospital in Seoul, Korea. General characteristics, clinical characteristics, attitude toward cancer, distress, and anxiety and depression scores of patients who joined an online health community (user group) and patients who did not (non-user group) were compared. The factors affecting online health community participation were education (p = 0.049), tumor size (p = 0.010), attitude toward cancer (p = 0.022), and anxiety and depression (p = 0.021). The average score of satisfaction with the online health community was 4.25 of 5. The user group had larger tumors, a high awareness of the risk of thyroid cancer, and high levels of anxiety and depression. Patients who actively used the online health community have relatively larger cancer size and had higher levels of mental stress. As such patients are often very anxious and depend heavily on the gathered information, the quality of this information is important. Healthcare professionals need to develop appropriate interventions for patients participating in the online health community.

Hippocampal Lipocalin 2 Is Associated With Neuroinflammation and Iron-Related Oxidative Stress in ob/ob Mice.

Obesity causes brain injuries with inflammatory and structural changes, leading to neurodegeneration. Although increased circulating lipocalin 2 (LCN2) level has been implicated in neurodegenerative diseases, the precise mechanism of neurodegeneration in obesity is not clear. Here, we investigated whether LCN2-mediated signaling promotes neurodegeneration in the hippocampus of leptin-deficient ob/ob mice, which are characterized by obesity, insulin resistance, systemic inflammation, and neuroinflammation. In particular, there was significant upregulation of both LCN2 and matrix metalloproteinase 9 levels from serum and hippocampus in ob/ob mice. Using RNA-seq analysis, we found that neurodegeneration- sortilin-related receptor 1 (Sorl1) and brain-derived neurotrophic factor (Bdnf) genes were significantly reduced in the hippocampus of ob/ob mice. We additionally found that the endosome-related WD repeat and FYVE-domain-containing 1 (Wdfy1) gene were upregulated in ob/ob mice. In particular, iron overload-related mitochondrial ferritin and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) proteins were increased in the hippocampus of ob/ob. Thus, these findings indicate that iron-binding protein LCN2-mediated oxidative stress promotes neurodegeneration in ob/ob mice.

Caloric restriction reverses left ventricular hypertrophy through the regulation of cardiac iron homeostasis in impaired leptin signaling mice.

Leptin-deficient and leptin-resistant mice manifest obesity, insulin resistance, and left ventricular hypertrophy (LVH); however, LVH's mechanisms are not fully understood. Cardiac iron dysregulation has been recently implicated in cardiomyopathy. Here we investigated the protective effects of caloric restriction on cardiac remodeling in impaired leptin signaling obese mice. RNA-seq analysis was performed to assess the differential gene expressions in the heart of wild-type and ob/ob mice. In particular, to investigate the roles of caloric restriction on iron homeostasis-related gene expressions, 10-week-old ob/ob and db/db mice were assigned to ad libitum or calorie-restricted diets for 12 weeks. Male ob/ob mice exhibited LVH, cardiac inflammation, and oxidative stress. Using RNA-seq analysis, we identified that an iron uptake-associated gene, transferrin receptor, was upregulated in obese ob/ob mice with LVH. Caloric restriction attenuated myocyte hypertrophy, cardiac inflammation, fibrosis, and oxidative stress in ob/ob and db/db mice. Furthermore, we found that caloric restriction reversed iron homeostasis-related lipocalin 2, divalent metal transporter 1, transferrin receptor, ferritin, ferroportin, and hepcidin expressions in the heart of ob/ob and db/db mice. These findings demonstrate that the cardioprotective effects of caloric restriction result from the cellular regulation of iron homeostasis, thereby decreasing oxidative stress, inflammation, and cardiac remodeling. We suggest that decreasing iron-mediated oxidative stress and inflammation offers new therapeutic approaches for obesity-induced cardiomyopathy.

Parafoveal and Peripapillary Perfusion Predict Visual Field Recovery in Chiasmal Compression due to Pituitary Tumors.

BACKGROUND: To evaluate the potential of vessel density alterations for predicting postoperative visual field (VF) improvement in chiasmal compression using optical coherence tomography angiography (OCT-A). METHODS: The study investigated 57 eyes of 57 patients diagnosed with pituitary tumors and 42 eyes of 42 age and refractive error matched controls. All eyes with chiasmal compression for which preoperative optical coherence tomography (OCT) and OCT-A, and pre- and postoperative VF data were available. Preoperative vessel densities of superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), and radial peripapillary capillary (RPC) segment were utilized by OCT-A. RESULTS: Preoperative peripapillary retinal nerve fiber layer and ganglion cell layer complex thickness and vessel densities of SRCP and RPC segments in eyes with chiasmal compression were significantly reduced compared with healthy controls (p < 0.001, p < 0.001, p = 0.007, and p = 0.020, respectively). In multivariate regression analysis, preoperative perimetric mean deviation (MD) (p = 0.002) and vessel density of SRCP (p = 0.025) were correlated significantly with postoperative perimetric MD. Spearman's correlation analysis revealed significant correlations between preoperative MD on perimetry (r = 0.443, p = 0.001), vessel densities of SRCP (r = 0.288, p = 0.035) and RPC segment (r = 0.347, p = 0.009), and postoperative perimetric MD. CONCLUSIONS: Structural degeneration referred to as microvascular alterations measured by OCT-A and preoperative VF defects were associated with worse postoperative VF prognosis. Parafoveal and peripapillary vessel densities may serve as a sensitive, structural prognostic factors in the preoperative judgement of chiasmal compression.