Statistical methods for handling nondetected results in food chemical monitoring data to improve food risk assessments.

Chemical risk assessment is important for risk management, and estimates of chemical exposure must be as accurate as possible. Chemical concentrations in food below the limit of detection are known as nondetects and result in left-censored data. During statistical analysis, the method used for handling values below the limit of detection is important. Many risk assessors employ widely used substitution methods to treat left-censored data, as recommended by international organizations. The National Institute of Food and Drug Safety Evaluation of South Korea also recommends these methods, which are currently used for chemical exposure assessments. However, these methods have statistical limitations, and international organizations recommend more advanced alternative statistical approaches. In this study, we assessed the validity of currently used statistical methods for handling nondetects. To identify the most suitable statistical method for handling nondetection, we created virtual data and conducted simulation studies. Based on both simulation and case studies, the Maximum Likelihood Estimation (MLE) and Robust Regression on Order Statistics (ROS) methods were found to be the best options. The statistical values obtained from these methods were similar to those obtained from the commonly used 1/2 Limit of Detection (LOD) substitution method for nondetection treatment. In three case studies, we compared the various methods based on the root mean squared error. The data for all case studies were from the same source, to avoid heterogeneity. Across various sample sizes and nondetection rates, the mean and 95th percentile values for all treatment methods were similar. However, "lognormal maximum likelihood estimation" method was not suitable for estimating the mean. Risk assessors should consider statistical processing of monitoring data to reduce uncertainty. Currently used substitution methods are effective and easy to apply to large datasets with nondetection rates <80%. However, advanced statistical methods are required in some circumstances, and national guidelines are needed regarding their use in risk assessments.

Adsorption of Hg(II) on polyethyleneimine-functionalized carboxymethylcellulose beads: Characterization, toxicity tests, and adsorption experiments.

Mercury (Hg) is widely used in many industrial processes and is released into the environment. Therefore, efficient removal of Hg from water is of vital importance worldwide. Here, we explored the adsorption characteristics of Hg(II) on polyethyleneimine-functionalized carboxymethylcellulose (PEI-CMC) beads and studied the toxicity of the beads toward Daphnia magna and Pseudokirchneriella subcapitata. The PEI-CMC beads had an average particle size of 2.04 ± 0.25 mm, a point of zero charge (pHpzc) of 5.8, and a swelling ratio of 2.45. Acute toxicity tests demonstrated that the PEI-CMC beads had no toxic effects on D. magna. The growth inhibition tests revealed that growth inhibition of P. subcapitata could be attributed to adsorption of trace elements in growth media on the PEI-CMC beads. The adsorption experiments exhibited that the Matthews and Weber model best described the kinetic data, whereas the Redlich-Peterson model was well fitted to the isotherm data. The theoretical maximum Hg(II) adsorption capacity of the PEI-CMC beads was 313.1 mg/g. The thermodynamic experiments showed endothermic nature of the Hg(II) adsorption on the PEI-CMC beads at 10-40 °C. The adsorption experiments exhibited that the Hg(II) adsorption capacity decreased gradually as pH increased from 2 to 12. The adsorption of Hg(II) on the PEI-CMC beads can occur through chelation and electrostatic attraction. The FTIR and XPS spectra before and after Hg(II) adsorption confirmed that chelation of neutral Hg(II) species (HgCl2, HgClOH, and Hg(OH)2) can occur with amino and oxygen-containing functional groups on the PEI-CMC beads. Considering species distribution of Hg(II) and the pHpzc of the PEI-CMC beads, electrostatic attraction between the positively-charged beads and anionic Hg(II) species (HgCl3- and HgCl42-) can take place in highly acidic solutions. The PEI-CMC beads were regenerated and reused for Hg(II) adsorption using 0.1 M HCl.

Acetaminophen adsorption to spherical carbons hydrothermally synthesized from sucrose: experimental, molecular, and mathematical modeling studies.

Acetaminophen (AAP) is an analgesic and non-steroidal anti-inflammatory drug and a micropollutant that has been detected in waterbodies worldwide. Here, we explore the characteristics of AAP adsorption onto spherical carbons (SCs) hydrothermally synthesized from pure sucrose as a carbon source. In one-factor-at-a-time experiments, the adsorption capacity of AAP remained relatively constant between pH 2 and 10 but became negligible at pH 12. The Raman, FTIR, and XPS spectra illustrate that hydrogen bonding, π-π interactions, and n-π* interactions could contribute to the AAP adsorption onto the SCs. CHEM3D modeling was used to explore hydrogen-bond formation, π-π interactions, n-π* interactions, and electrostatic repulsion between AAP and the SCs. In view of the pHpzc of the SCs (3.1) and the pKa of AAP (10.96), electrostatic repulsion could occur between negatively charged SCs and anionic AAP above pH 10. In consideration of the average pore diameter of the SCs (1.89 nm) and the AAP molecular size (8.94 Å × 7.95 Å × 4.93 Å), a pore-filling mechanism could contribute to the adsorption. A pseudo-second-order model was best fitted to the kinetic data (equilibrium time = 6 h), whereas the Liu isotherm was most suitable for the equilibrium data (maximum adsorption capacity = 92.0 mg/g). Adsorption of AAP to the SCs was exothermic at 10-40 °C. The SCs were regenerated and reused for AAP adsorption using a methanol. Multiple-factor-at-once (MFAO) experiments (input variables: pH, temperature, adsorbent dosage, and initial AAP concentration; output: AAP adsorption capacity) were used to develop response surface methodology (RSM, quartic regression) and artificial neural network (ANN, topology 4:11:9:1) models. Analyses using additional MFAO experimental data reveal that the predictive ability of the ANN model (R2 = 0.890) was better than that of the RSM model (R2 = 0.764). Based on the weight values of the ANN model, the relative importance of the input variables on the output was quantified in the order of initial AAP concentration (100%) > adsorbent dosage (92.3%) > temperature (77.6%) > pH (43.6%).

CD34dim cells identified as pluripotent stem cell-derived definitive hemogenic endothelium purified using bone morphogenetic protein 4.

Hemogenic endothelium (HE) plays a pivotal and inevitable role in haematopoiesis and can generate all blood and endothelial lineage cells in the aorta-gonad-mesonephros of mouse embryos. Whether definitive HE can prospectively isolate pure HE from human pluripotent stem cells that can spontaneously differentiate into heterogeneous cells remains unknown. Here, we identified and validated a CD34dim subpopulation with hemogenic potential. We also purified CD34 cells with a CXCR4- CD73- phenotype as a definitive HE population that generated haematopoietic stem cells and lymphocytes. The frequency of CXCR4- CD73- CD34dim was evidently increased by bone morphogenetic protein 4, and purified HE cells differentiated into haematopoietic cells with myeloid and T lymphoid lineages including Vδ2+ subset of γ/δ T cells. We developed a simple method to purify HE cells that were enriched in CD34dim cells. We uncovered an initial step in differentiating haematopoietic lineage cells that could be applied to basic and translational investigations into regenerative medicine.

Characterization of ibuprofen removal by calcined spherical hydrochar through adsorption experiments, molecular modeling, and artificial neural network predictions.

Ibuprofen (IPF) is one of the most prescribed nonsteroidal anti-inflammatory drugs in recent times, but it is not readily removed in conventional wastewater treatments. Here, we investigate the adsorption characteristics of IPF onto calcined spherical hydrochar (CSH), which was synthesized through hydrothermal carbonization of sucrose followed by calcination. The adsorption experiments show that the equilibration time for IPF was 360 min, and a pseudo-second-order model was best fitted to the kinetic data. The isotherm data were best described by the Liu model with a theoretical maximum adsorption capacity of 95.6 mg/g. The thermodynamic data indicate the endothermic nature of the adsorption at 10-40 °C. The CSH was favorably regenerated and reused using methanol. In pH experiments, the IPF adsorption capacity declined gradually as pH rose from 2 to 8, dropped rapidly at pH 10, and became negligible at pH 12. The IPF adsorption to the CSH could occur through various adsorption mechanisms. Hydrogen-bond formation, π-π interactions, n-π* interactions, and electrostatic repulsion were explored and visualized with molecular modeling using CHEM3D. The Raman, FTIR, and XPS spectra suggest that π-π interactions could take place between the CSH and IPF. Considering the pKa value of IPF (4.91) and pHiep of the CSH (3.21), electrostatic repulsion between the negatively-charged CSH and anionic IPF could play a negative role in the adsorption. A pore-filling mechanism could contribute to the adsorption in view of the molecular size of IPF (9.43 Å × 7.75 Å × 6.23 Å) and the average pore diameter of the CSH (2.27 nm). In addition, hydrophobic interactions could be involved in the adsorption. Multi-factor adsorption experiments were executed with pH, temperature, CSH dosage, and initial IPF concentrations as input variables and IPF removal rate as an output variable, and an artificial neural network (ANN) model with a topology of 4:9:11:1 was developed to sufficiently describe the adsorption data (R > 0.99). Further analyses with additional experimental data confirm that the ANN model possessed good predictability for multi-factor adsorption.

Subcritical Water Hydrolysis of Comb Pen Shell (Atrina pectinata) Edible Parts to Produce High-Value Amino Acid Products.

Artina pectinata (Comb pen shell, CPS) is a high-protein source that contains a variety of essential amino acids. Subcritical water hydrolysis (SWH) was used to recover amino acids from the posterior adductor muscle (PAM), anterior adductor muscle (ADM), and mantle. The temperatures ranged from 120 °C to 200 °C, and the pressure and time of hydrolysis were 3 MPa and 30 min, respectively. Further characterization of the hydrolysates was performed to ascertain amino acid profiles and biofunctional properties. The hydrolysates contained more free amino acids than the untreated samples. Antioxidant activity of treated samples increased as SW temperatures increased. At 200 °C, those inhibiting ACE had a maximum antihypertensive activity of 200 °C in 1% PAM, ADM, and mantle with 85.85 ± 0.67, 84.55 ± 0.18, and 82.15 ± 0.85%, respectively, compared to 97.57 ± 0.67% in 1% standard captopril. Perhaps the most significant finding was the predominance of taurine in the three parts following SW treatment at 120 °C. The hydrolysates may be of considerable interest for use in food or energy drinks. SWH demonstrates efficacy in recovering amino acids, particularly taurine, from edible parts of A. pectinata.

Extraction of edible oils and amino acids from eel by-products using clean compressed solvents: An approach of complete valorization.

Green extraction methodologies using supercritical carbon dioxide (SC-CO2) and subcritical water were used to valorize Conger myriaster skin (CMS). The omega-3 fatty acid content in CMS oil extracted using SC-CO2 was 18.62 ± 0.08%, and vitamin A, D, E, and K2 contents were 467.38 ± 0.46 µg/100 g, 8.31 ± 0.02 mg/100 g, 143.42 ± 4.61 mg/100 g, and 1.27 ± 0.05 mg/100 g, respectively. De-oiled CMS was hydrolyzed using subcritical water at temperatures ranging from 160 to 280 °C. Total protein, total sugar, and Maillard reaction product contents reached maximum values of 409.31 ± 2.86 mg bovine serum albumin (BSA)/g at 190 °C, 8.31 ± 0.31 mg glucose/g at 280 °C, and 0.240 ± 0.003 (Abs420nm) at 220 °C, respectively. The highest antioxidant activity was observed at 280 °C. Free amino acids were abundant in the hydrolysates. Oil extraction from CMS using supercritical and subcritical fluids represents an effective and economical source of functional materials.

Medial prefrontal cortex and anteromedial thalamus interaction regulates goal-directed behavior and dopaminergic neuron activity.

The prefrontal cortex is involved in goal-directed behavior. Here, we investigate circuits of the PFC regulating motivation, reinforcement, and its relationship to dopamine neuron activity. Stimulation of medial PFC (mPFC) neurons in mice activated many downstream regions, as shown by fMRI. Axonal terminal stimulation of mPFC neurons in downstream regions, including the anteromedial thalamic nucleus (AM), reinforced behavior and activated midbrain dopaminergic neurons. The stimulation of AM neurons projecting to the mPFC also reinforced behavior and activated dopamine neurons, and mPFC and AM showed a positive-feedback loop organization. We also found using fMRI in human participants watching reinforcing video clips that there is reciprocal excitatory functional connectivity, as well as co-activation of the two regions. Our results suggest that this cortico-thalamic loop regulates motivation, reinforcement, and dopaminergic neuron activity.

Decision Tree Algorithm-Based Prediction of Vulnerability to Depressive and Anxiety Symptoms in Caregivers of Children With Glaucoma.

PURPOSE: Development and validation of a decision tree model (DTM) for prediction of mental health status in Korean caregivers of children with glaucoma. DESIGN: Cross-sectional study. METHODS: Caregivers of children younger than 18 years with diagnosed primary childhood glaucoma (n = 42), secondary childhood glaucoma (n = 51), and glaucoma suspect (GS; n = 36) were prospectively enrolled at Seoul National University Children's Hospital, Seoul, Korea. The participants completed 2 questionnaires, the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder (GAD-7) Assessment. A DTM analysis for discrimination of those with moderate-to-severe depressive (PHQ-9 score ≥10) and anxiety (GAD-7 score ≥11) symptoms was performed with recursive partitioning algorithms based on the obtained clinical, demographic, and socioeconomic data. RESULTS: The mean PHQ-9 and GAD-7 scores did not significantly differ among the 3 groups (P = .823 for PHQ-9 score; P = .730 for GAD-7 score). The DTM's balanced accuracies were 0.875 (95% CI = 0.778-0.972) for the PHQ-9 score and 0.880 (95% CI = 0.800-0.960) for theGAD-7 score. The DTM of the PHQ-9 revealed that in caregivers of children with glaucoma, depressive symptoms should be strongly suspected when (1) the child has undergone more than 2 glaucoma surgeries; or (2) the visual acuity (VA, converted to logarithm of minimum angle of resolution [logMAR]) in the better eye is worse than 0.4 if the child has had only 1 or no surgery. CONCLUSIONS: Evaluation of the number of glaucoma surgeries and VA in the better eye can be a useful decision support tool in predicting mental illness in caregivers of children with glaucoma.

Ocular Manifestations, Visual Field Pattern, and Visual Field Test Performance in Traumatic Brain Injury and Stroke.

PURPOSE: To analyze ocular manifestations, visual field (VF) pattern, and VF test performance in traumatic brain injury (TBI) and stroke patients. METHODS: This retrospective, cross-sectional study included 118 patients (236 eyes) with TBI and stroke who had undergone VF testing by standard automated perimetry with the central 24-2 threshold test. Clinical features including best-corrected visual acuity (BCVA), intraocular pressure (IOP), ocular manifestations, and VF test results including VF defect pattern, reliability, and global indices were analyzed and compared between the TBI and stroke patients. RESULTS: In TBI patients, ocular manifestations included strabismus (11.1%), cataract (4.2%), and glaucoma suspect (2.8%), whereas in stroke patients, cataract (15.2%), strabismus (8.5%), diabetic retinopathy (4.9%), extraocular movement (EOM) limitation (3.0%), glaucoma suspect (3.0%), nystagmus (2.4%), drusen (1.2%), and vitreous hemorrhage (1.2%) were found. The VF test results showed that 47 eyes (85.5%) in TBI and 86 (65.2%) in stroke had VF defect; in TBI, the scattered pattern was the most common (56.4%), followed by homonymous hemianopsia (14.5%), homonymous quadrantanopia (10.9%), and total defect (3.6%), whereas in stroke, homonymous hemianopsia was the most common (31.8%), followed by scattered pattern (16.7%), homonymous quadrantanopia (12.1%), and total defect (4.5%). Only 15 eyes (27.3%) in TBI and 32 (24.2%) in stroke showed reliable VF indices. The mean deviation (MD) was -10.5 ± 7.1 dB in TBI and -9.5 ± 6.8 dB in stroke, and the pattern standard deviation (PSD) was 4.9 ± 3.3 dB in TBI and 6.1 ± 3.9 dB in stroke, without statistically significant differences between the two groups. CONCLUSION: Various ocular manifestations were found, and a considerable proportion of patients were experiencing VF defects and showed unreliable VF test performance. Our findings suggest that accurate evaluation and rehabilitation of visual function should be a matter of greater concern and emphasis in the management of TBI and stroke patients, besides systemic diseases.

Genetic Risk and Phenotype Correlation of Primary Open-Angle Glaucoma Based on Rho-Kinase Gene Polymorphisms.

Rho-associated coiled-coil kinase (ROCK) signaling can affect glaucoma risk by regulating trabecular meshwork outflow. We investigated the effect of ROCK gene polymorphism on the risks of primary open-angle glaucoma (POAG) and POAG-related phenotypes including intraocular pressure (IOP) in a Korean population. A total of 24 single-nucleotide polymorphisms (SNPs) from ROCK1 and ROCK2 were selected and genotyped for 363 POAG patients and 213 healthy controls. Among the 363 POAG patients, 282 were normal-tension glaucoma (NTG, baseline IOP ≤ 21 mmHg) and 81 were high-tension glaucoma (HTG, baseline IOP > 21 mmHg). The SNPs rs288979, rs1006881, rs35996865, rs10083915, and rs11873284 in ROCK1 (tagged to each other, r2 = 1) were nominally associated with risk of HTG (OR = 0.52, p = 0.045). However, there were no SNPs that were significantly associated with the risk of NTG. In the genotype-phenotype correlation analysis, the SNPs rs2230773 and rs3771106 in ROCK2 were significantly correlated with central corneal thickness (CCT)-adjusted IOP (p = 0.024) and axial length (AXL; p = 0.024), respectively. The present data implicated the role of ROCK in POAG development, and as such, can serve as a good reference for upcoming Rho/ROCK-pathway-related studies on POAG.

Amino Acid Profiles and Biopotentiality of Hydrolysates Obtained from Comb Penshell (Atrina pectinata) Viscera Using Subcritical Water Hydrolysis.

The recovery of amino acids and other important bioactive compounds from the comb penshell (Atrina pectinata) using subcritical water hydrolysis was performed. A wide range of extraction temperatures from 140 to 290 °C was used to evaluate the release of proteins and amino acids. The amount of crude protein was the highest (36.14 ± 1.39 mg bovine serum albumin/g) at 200 °C, whereas a further increase in temperature showed the degradation of the crude protein content. The highest amount of amino acids (74.80 mg/g) was at 230 °C, indicating that the temperature range of 170-230 °C is suitable for the extraction of protein-rich compounds using subcritical water hydrolysis. Molecular weights of the peptides obtained from comb penshell viscera decreased with the increasing temperature. SDS-PAGE revealed that the molecular weight of peptides present in the hydrolysates above the 200 °C extraction temperature was ≤ 1000 Da. Radical scavenging activities were analyzed to evaluate the antioxidant activities of the hydrolysates. A. pectinata hydrolysates also showed a particularly good antihypertensive activity, proving that this raw material can be an effective source of amino acids and marine bioactive peptides.

Metal-organic framework MIL-100(Fe) for dye removal in aqueous solutions: Prediction by artificial neural network and response surface methodology modeling.

In this study, a metal organic framework MIL-100(Fe) was synthesized for rhodamine B (RB) removal from aqueous solutions. An experimental design was conducted using a central composite design (CCD) method to obtain the RB adsorption data (n = 30) from batch experiments. In the CCD approach, solution pH, adsorbent dose, and initial RB concentration were included as input variables, whereas RB removal rate was employed as an output variable. Response surface methodology (RSM) and artificial neural network (ANN) modeling were performed using the adsorption data. In RSM modeling, the cubic regression model was developed, which was adequate to describe the RB adsorption according to analysis of variance. Meanwhile, the ANN model with the topology of 3:8:1 (three input variables, eight neurons in one hidden layer, and one output variable) was developed. In order to further compare the performance between the RSM and ANN models, additional adsorption data (n = 8) were produced under experimental conditions, which were randomly selected in the range of the input variables employed in the CCD matrix. The analysis showed that the ANN model (R2 = 0.821) had better predictability than the RSM model (R2 = 0.733) for the RB removal rate. Based on the ANN model, the optimum RB removal rate (>99.9%) was predicted at pH 5.3, adsorbent dose 2.0 g L-1, and initial RB concentration 73 mg L-1. In addition, pH was determined to be the most important input variable affecting the RB removal rate. This study demonstrated that the ANN model could be successfully employed to model and optimize RB adsorption to the MIL-100(Fe).

Impact of imatinib or dasatinib coadministration on in vitro preantral follicle development and oocyte acquisition in cyclophosphamide-treated mice.

OBJECTIVE: We investigated the impact of tyrosine kinase inhibitor (imatinib or dasatinib) coadministration with cyclophosphamide (Cp) on preantral follicle development in an in vitro mouse model. METHODS: Seventy-three female BDF1 mice were allocated into four experimental groups: group A, saline; group B, Cp (25 mg/kg); group C, Cp (25 mg/kg) and imatinib (7.5 mg/kg); and group D, Cp (25 mg/kg) and dasatinib (7.5 mg/kg). Preantral follicles were isolated and cultured in vitro up to 12 days. Final oocyte acquisition and spindle integrity of metaphase II (MII) oocytes were assessed. Levels of 17ß-estradiol and anti-Müllerian hormone (AMH) in the final spent media were measured by enzyme-linked immunosorbent assays, and the mRNA levels of Star, Sod1, Mapk3, and Casp3 in the final follicular cells were quantified by real-time polymerase chain reaction. RESULTS: The percentage of MII oocytes per initiated follicle, the proportion of MII oocytes with normal spindles, and the 17ß-estradiol level were similar in all four groups. The median AMH level in group B (7.74 ng/mL) was significantly lower than that in group A (10.84 ng/mL). However, the median AMH levels in group C (9.96 ng/mL) and group D (9.71 ng/mL) were similar to that in group A. The mRNA expression levels of Star, Sod1, Mapk3, and Casp3 were similar in all four groups. CONCLUSION: Coadministration of imatinib or dasatinib with Cp could preserve AMH production capacity in this in vitro mice preantral follicle culture model, and it did not affect MII oocyte acquisition.

Detection of infectious hypodermal and hematopoietic necrosis virus and white spot syndrome virus in whiteleg shrimp (Penaeus vannamei) imported from Vietnam to South Korea.

In this study, whiteleg shrimp (Penaeus vannamei) imported from Vietnam were collected from South Korean markets, and examined for 2 viruses: infectious hypodermal and hematopoietic necrosis virus (IHHNV, recently classified as decapod penstyldensovirus-1), and white spot syndrome virus (WSSV). Among 58 samples, we detected IHHNV in 23 samples and WSSV in 2 samples, using polymerase chain reaction and sequencing analyses. This is the first report of IHHNV and WSSV detection in imported shrimp, suggesting that greater awareness and stricter quarantine policies regarding viruses infecting shrimp imported to South Korea are required.

Effects of dynamic oxygen concentrations on the development of mouse pre- and peri-implantation embryos using a double-channel gas supply incubator system.

OBJECTIVE: We aimed to evaluate the effects of different oxygen conditions (20% [high O2], 5% [low O2] and 5% decreased to 2% [dynamic O2]) on mouse pre- and peri-implantation development using a novel double-channel gas supply (DCGS) incubator (CNC Biotech Inc.) to alter the oxygen concentration during in vitro culture. METHODS: The high-O2 and low-O2 groups were cultured from the one-cell to the blastocyst stage under 20% and 5% oxygen concentrations, respectively. In the dynamic-O2 group, mouse embryos were cultured from the one-cell to the morula stage under 5% O2 for 3 days, followed by culture under 2% O2 to the blastocyst stage. To evaluate peri-implantation development, the blastocysts from the three groups were individually transferred to a fibronectin-coated dish and cultured to the outgrowth stage in droplets. RESULTS: The blastocyst formation rate was significantly higher in the low-O2 and dynamic-O2 groups than in the high-O2 group. The total cell number was significantly higher in the dynamic-O2 group than in the low-O2 and high-O2 groups. Additionally, the apoptotic index was significantly lower in the low-O2 and dynamic-O2 groups than in the high-O2 group. The trophoblast outgrowth rate and spread area were significantly higher in the low-O2 and dynamic-O2 groups than in the high-O2 group. CONCLUSION: Our results showed that a dynamic oxygen concentration (decreasing from 5% to 2%) had beneficial effects on mouse pre- and peri-implantation development. Optimized, dynamic changing of oxygen concentrations using the novel DCGS incubator could improve the developmental competence of in vitro cultured embryos in a human in vitro fertilization and embryo transfer program.

Contact Lens Induced Limbal Stem Cell Deficiency: Clinical Features in Korean Patients.

PURPOSE: To describe the clinical features of Korean patients with contact lens-induced limbal stem cell deficiency (CL-LSCD). METHODS: Medical records of 22 patients who were diagnosed with CL-LSCD between 2014 and 2019 were reviewed retrospectively. Outcome measures included demographics, clinical presentation, treatment, clinical course, and pattern of contact lens (CL) wear. RESULTS: Forty-two eyes of 22 patients were found to have typical changes associated with CL-LSCD. Twenty (91%) patients were women and mean age was 36 ± 12 years. All patients had myopia with mean spherical equivalent of -7.52 ± 3.2 diopter. Twenty (91%) patients had bilateral disease and the location of limbal involvement was diffuse in 20 eyes (47.6%) and partial in 22 eyes (52.4%, superior in 20 eyes and inferior in 2 eyes). Fourteen (63.6%) patients complained of decreased visual acuity. Average period of CL wear was 14 ± 9 years. Four patients used cosmetic colored CLs and four patients had a history of overnight CL wear. All 12 patients who completed follow-up (28 ± 42 weeks) showed improvement in visual acuity and ocular surface condition after cessation of CL wear and medical treatment. Of them, five (42%) patients showed full recovery while seven (58%) showed partial recovery. CONCLUSIONS: If a patient with a history of CL wear for an extended period of time presents with decreased visual acuity, practitioners should perform detailed examinations with suspicion of CL-LSCD, including fluorescein staining. CL-LSCD is usually reversible and close follow-up with conservative treatment is recommended as the initial treatment option.

Basolateral amygdala neurons are activated during threat expectation.

Fear conditioning studies have led to the view that the amygdala contains neurons that signal threat and in turn elicit defensive behaviors through their brain stem and hypothalamic targets. In agreement with this model, a prior unit-recording study in rats performing a seminaturalistic foraging task revealed that many lateral amygdala (LA) neurons are predator responsive. In contrast, our previous study emphasized that most basolateral (BL) amygdala neurons are inhibited at proximity of the predator. However, the two studies used different methods to analyze unit activity, complicating comparisons between them. By applying the same method to the sample of BL neurons we recorded previously, the present study revealed that most principal cells are inhibited by the predator and only 4.5% are activated. Moreover, two-thirds of these cells were also activated by nonthreatening stimuli. In fact, fitting unit activity with a generalized linear model revealed that the only task variables associated with a prevalent positive modulation of BL activity were expectation of the predator's presence and whether the prior trial had been a failure or success. At odds with the threat-coding model of the amygdala, actual confrontation with the predator was usually associated with a widespread inhibition of principal BL neurons. NEW & NOTEWORTHY The basolateral amygdala (BL) is thought to contain neurons that signal threat, in turn eliciting defensive behaviors. In contrast, the present study reports that very few principal BL cells are responsive to threats and that most of them are also activated by nonthreatening stimuli. Yet, expectation of the threat's presence was associated with a prevalent positive modulation of BL activity; actual confrontation with the threat was associated with a widespread inhibition.

Vigilance-Associated Gamma Oscillations Coordinate the Ensemble Activity of Basolateral Amygdala Neurons.

Principal basolateral amygdala (BL) neurons profoundly influence motivated behaviors, yet few of them are activated by emotionally valenced stimuli. Here, we show that a likely explanation for this paradox is the synchronizing influence of the high-gamma rhythm. High-gamma (75-95 Hz) entrained BL firing more strongly than all other rhythms. It was most pronounced during states of increased vigilance, when rats were apprehensive. Relative to behavioral states, high-gamma produced minor changes in firing rates yet dramatic increases in synchrony. Moreover, connected pairs of cells showed similarly high levels of entrainment and synchronization. Unexpectedly, prefrontal- and accumbens-projecting cells, respectively, showed high and low entrainment by high-gamma, indicating that this rhythm differentially synchronizes the activity of BL neurons projecting to specific sites. Overall, our findings suggest that individual BL neurons encode information not only by changing their firing rates, but also by synchronizing their collective activity, amplifying their impact on target structures.

Differential Recruitment of Competing Valence-Related Amygdala Networks during Anxiety.

The basolateral amygdala (BL) is involved in fear and anxiety, but it is currently unclear how the same network supports these two states. To address this question, we trained rats on appetitive and aversive conditioning in different contexts. Distinct groups of BL neurons displayed increased activity during appetitive (CS-R) versus aversive (CS-S) conditioned stimuli (R cells and S cells, respectively), and they were typically inhibited by the other CS. When the CS-S was presented in the safe context, rats entered a long-lasting, anxiety-like state characterized by increased inter-CS freezing and impaired reward seeking. During this state, a subset of BL cells ("state cells") showed sustained shifts in baseline activity whose time course matched that of the behavioral changes. Many state cells with increased firing rates were S cells, whereas R cells only included state cells with reduced firing rates. Thus, anxiety involves persistent activity changes that are differentially expressed by subsets of valence-specific BL neurons.