A novel surgical approach using the "lateral corridor" for minimally invasive oblique lumbar interbody fusion at L5-S1: a clinical series and technical note.

PURPOSE: The minimally invasive oblique lumbar interbody fusion (MI-OLIF) L5-S1 was introduced to overcome the limitations of conventional fusion techniques, however, MI-OLIF is not possible using the standard method due to vascular structures in some cases. We aimed to introduce the "lateral corridor" and report the details of the surgical technique with a clinical case series. METHODS: We utilized the lateral access route of the left common iliac vein and named it the "lateral corridor", to distinguish the technique from the standard technique (central corridor). The type and frequency of branch vessels that required additional manipulations were reviewed, and the frequency of intraoperative vascular injury was investigated. RESULTS: Among the 107 patients who underwent MI-OLIF L5-S1, 26 patients (24.3%) who received the "lateral corridor" technique were included. Branch vessel ligation was required in 42.3% of the patients. The types of branch vessels that required ligation were seven cases (26.9%) of the iliolumbar vein (ILV) and six cases (23.1%) of ascending lumbar vein (ALV). The ILV and ALV were ligated in two cases. None of the patients developed intraoperative vascular injuries. CONCLUSION: We introduced the "lateral corridor" as an alternative approach for MI-OLIF L5-S1, implemented it in 24.3% of the patient cohort, and reported favorable outcomes devoid of vascular complications. The "lateral corridor" necessitated ligation of the ILV or ALV in 42.3% of cases. The "lateral corridor" approach appears to be a promising surgical technique, offering feasibility even in instances where the vascular anatomy precludes the employment of the conventional approach.

Multiple Cerebral Infarctions and Rhabdomyolysis After Sildenafil Citrate (Viagra®) Intoxication: A Case Report.

BACKGROUND: Sildenafil citrate (Viagra®) is used to treat male erectile dysfunction; however, little is known about the effects of sildenafil overdose and intoxication. We report a patient who presented with cerebral infarction and rhabdomyolysis after intentional sildenafil intoxication. CASE REPORT: A 61-year-old man visited the Emergency Department complaining of dysarthria about 1 h after taking more than 30 sildenafil tablets with the intention to commit suicide. Dysarthria and dizziness were observed, but there were no other neurological symptoms. The creatine kinase level was elevated to 3118 U/L, and the patient was diagnosed with rhabdomyolysis. Brain magnetic resonance imaging revealed multiple scattered acute cerebral infarctions in both midbrain artery branches. At 4 h post-intoxication, the dysarthria had improved and we initiated dual antiplatelet therapy for cerebral infarction. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should be able to anticipate and treat complications like cerebral infarction and rhabdomyolysis after sildenafil intoxication.

SYMPATHETIC NERVE ENTRAPMENT POINT INJECTION AS AN ADJUVANT TREATMENT FOR INTRACTABLE CLUSTER HEADACHE: A CASE REPORT.

BACKGROUND: Cluster headache (CH) is characterized by severe unilateral pain ranging from the orbital to the temporal regions with ipsilateral autonomic manifestations. Although most patients respond to drugs or oxygen inhalation, some do not. In this case report, we introduce sympathetic nerve entrapment point injection (SNEPI), a new adjuvant treatment for CH. CASE REPORT: We introduce two CH patients who did not respond well to pharmacological treatment or 100% oxygen inhalation, but who improved after SNEPI. Patient 1, a 42-year-old man, visited the Emergency Department (ED) with severe periorbital right frontal headache accompanied by ipsilateral rhinorrhea, conjunctival injection, and eyelid edema. The symptoms did not fully respond to drugs or oxygen inhalation, but improved after SNEPI into the tender point of the splenius capitis (SC) muscle; there was no further pain for 1 month thereafter. Patient 2, a 26-year-old woman, presented to the ED complaining of severe headache in the right supraorbital-temporal-occipital region with ipsilateral lacrimation and conjunctival congestion. The patient was taking various drugs for CH, but there was no improvement; the symptoms improved dramatically after SNEPI into the tender points of the SC and paraspinal deep muscles (levels T1-2), and the pain was well managed with reduced drug doses for 3 months. Why Should an Emergency Physician Be Aware of This? CH can cause severe acute pain, and sometimes pharmacological treatment or oxygen inhalation is not effective. SNEPI, which is inexpensive and can be easily performed, may be considered as an adjuvant treatment for intractable CH in the ED.

Adaptive designs for IVPT data with mixed scaled average bioequivalence.

In vitro permeation tests (IVPT) offer accurate and cost-effective development pathways for locally acting drugs, such as topical dermatological products. For assessment of bioequivalence, the FDA draft guidance on generic acyclovir 5% cream introduces a new experimental design, namely the single-dose, multiple-replicate per treatment group design, as IVPT pivotal study design. We examine the statistical properties of its hypothesis testing method-namely the mixed scaled average bioequivalence (MSABE). Meanwhile, some adaptive design features in clinical trials can help researchers make a decision earlier with fewer subjects or boost power, saving resources, while controlling the impact on family-wise error rate. Therefore, we incorporate MSABE in an adaptive design combining the group sequential design and sample size re-estimation. Simulation studies are conducted to study the passing rates of the proposed methods-both within and outside the average bioequivalence limits. We further consider modifications to the adaptive designs applied for IVPT BE trials, such as Bonferroni's adjustment and conditional power function. Finally, a case study with real data demonstrates the advantages of such adaptive methods.

Long-Term Clinical and Radiological Outcomes of Minimally Invasive Transforaminal Lumbar Interbody Fusion: 10-Year Follow-up Results.

BACKGROUND: Many studies have reported that minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) provides satisfactory treatment comparable to other fusion methods. However, in the case of MI-TLIF, there are concerns about the long-term outcome compared to conventional bilateral PLIF due to the small amount of disc removal and the lack of autogenous bone graft. Long-term follow-up studies are still lacking as most of the previous reports have follow-up periods of up to 5 years. METHODS: Thirty patients who underwent MI-TLIF were followed up for > 10 years (mean, 11.1 years). Interbody fusion rates were determined using a modified Bridwell grading system. Adjacent segment disease (ASD) was defined as radiological adjacent segment degeneration (R-ASDeg) as seen on plain X-rays; reoperated adjacent segment disease referred to the subsequent need for revision surgery. Clinical outcomes after surgery were assessed based on back and leg pain as well as the Oswestry disability index (ODI). RESULTS: The overall radiological fusion rate, at the 1-, 5-, and 10-year follow-up was 77.1%, 91.4%, and 94.3%, respectively. The incidence of R-ASDeg 1, 5, and 10 years after surgery was 6.7%, 16.7%, and 43.3% at the proximal adjacent segment and 4.8%, 14.3%, and 28.6% at the distal adjacent segment, respectively. R-ASDeg at either the proximal or distal segment was determined in 50.0% of the patients 10 years postoperatively. All clinical parameters improved significantly during follow-up, although the ODI and the visual analog scale (VAS) for leg pain at the 10-year follow-up were significantly worse in the R-ASDeg group than in the other patients (P = 0.009, P = 0.040). CONCLUSION: MI-TLIF improved both clinical and radiological outcomes, and the improvements were maintained for up to 10 years after surgery. However, R-ASDeg developed in up to 50% of the patients within 10 years, and both leg pain on the VAS and the ODI were worse in patients with R-ASDeg.

Vitamin D Receptor Activation in Liver Macrophages Protects Against Hepatic Endoplasmic Reticulum Stress in Mice.

BACKGROUND AND AIMS: Hepatic endoplasmic reticulum (ER) stress, whether triggered by intrinsic or extrinsic factors, can be resolved by the unfolded protein response (UPR). Sustained UPR activation leads to cell death and inflammatory response and contributes to liver disease progression. Hepatic tissue macrophages are key players in orchestrating liver inflammation, and ER stress can enhance macrophage activation. However, it is not well defined how the interplay between ER stress and inflammation is regulated during hepatic stress response. APPROACH AND RESULTS: Here we demonstrate that vitamin D receptor (VDR) activation mitigates hepatic ER stress response, whereas VDR knockout mice undergo persistent UPR activation and apoptosis in response to chemical ER stress inducer. Moreover, VDR deficiency promotes hepatic macrophage infiltration and increases gene expression and systematic levels of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor α. VDR expression is induced in hepatic macrophages by ER stress, and VDR plays a dual regulatory role in macrophages by protecting against ER stress and promoting anti-inflammatory polarization. Co-culture with VDR-activated bone marrow-derived macrophages suppresses UPR target genes in primary hepatocytes treated with ER stress inducers. Thus, the immunomodulatory functions of VDR in macrophages are critical in hepatic ER stress resolution in mice. CONCLUSIONS: VDR signaling in macrophages regulates a shift between proinflammatory and anti-inflammatory activation during ER stress-induced inflammation to promote hepatic ER stress resolution.

Methyl-Sensing Nuclear Receptor Liver Receptor Homolog-1 Regulates Mitochondrial Function in Mouse Hepatocytes.

BACKGROUND AND AIMS: Liver receptor homolog-1 (LRH-1; NR5A2) is a nuclear receptor that regulates metabolic homeostasis in the liver. Previous studies identified phosphatidylcholines as potential endogenous agonist ligands for LRH-1. In the liver, distinct subsets of phosphatidylcholine species are generated by two different pathways: choline addition to phosphatidic acid through the Kennedy pathway and trimethylation of phosphatidylethanolamine through phosphatidylethanolamine N-methyl transferase (PEMT). APPROACH AND RESULTS: Here, we report that a PEMT-LRH-1 pathway specifically couples methyl metabolism and mitochondrial activities in hepatocytes. We show that the loss of Lrh-1 reduces mitochondrial number, basal respiration, beta-oxidation, and adenosine triphosphate production in hepatocytes and decreases expression of mitochondrial biogenesis and beta-oxidation genes. In contrast, activation of LRH-1 by its phosphatidylcholine agonists exerts opposite effects. While disruption of the Kennedy pathway does not affect the LRH-1-mediated regulation of mitochondrial activities, genetic or pharmaceutical inhibition of the PEMT pathway recapitulates the effects of Lrh-1 knockdown on mitochondria. Furthermore, we show that S-adenosyl methionine, a cofactor required for PEMT, is sufficient to induce Lrh-1 transactivation and consequently mitochondrial biogenesis. CONCLUSIONS: A PEMT-LRH-1 axis regulates mitochondrial biogenesis and beta-oxidation in hepatocytes.

Optimal sessions of hyperbaric oxygen therapy in patients with carbon monoxide poisoning: A prospective observational study.

INTRODUCTION: Hyperbaric oxygen (HBO) therapy may be a useful treatment to prevent the development of delayed neuropsychiatric sequelae (DNS) in patients with acute carbon monoxide (CO) poisoning. However, there is no clear consensus regarding the optimal number of HBO therapy sessions in patients with CO poisoning. Here, we compared the development of DNS after 3 and > 3 sessions of HBO therapy in patients with acute CO poisoning. METHODS: This prospective observational study recruited 299 patients with CO poisoning. Demographic and clinical information were obtained, including comorbidities, vital signs, and symptoms. Patients were divided into two groups according to whether they received 3 or > 3 sessions of HBO therapy (3 HBO vs. >3 HBO). A propensity score-matching process was used to balance potential prognostic factors in both groups. RESULTS: Of the 299 patients with acute CO poisoning enrolled in this study, 183 (59.0%) were included in the analysis. Patients were excluded for the following reasons: age < 18 years, not underwent HBO therapy, discharged against medical advice, and loss to follow-up. The overall rate of DNS development was 17.5%. The >3 HBO group had a higher incidence of DNS development compared to the 3 HBO group (36.3% vs. 16.3%; p = 0.09). Propensity score-matching analysis revealed similar incidences of DNS (31.3% vs. 28.1%, respectively; p > 0.99). CONCLUSIONS: There is a critical need to determine the optimal number of HBO therapy sessions for patients with acute CO poisoning. This study showed no difference in DNS development after 3 and > 3 sessions of HBO therapy.

Hyperbaric Oxygen Therapy Did Not Prevent Delayed Neuropsychiatric Sequelae in a Prospective Observational Study With Propensity Score Matching in 224 Patients With Acute Carbon Monoxide Toxicity.

BACKGROUND: It is important to prevent the development of delayed neuropsychiatric sequelae (DNS) in acute carbon monoxide (CO) intoxication, but no effective treatment has been clearly identified. Hyperbaric oxygen (HBO) therapy is one of the treatment options in acute CO poisoning; however, whether it can prevent the development of DNS is controversial. OBJECTIVES: The purpose of this study is to compare the effectiveness of normobaric oxygen (NBO) and HBO in preventing DNS. METHODS: This prospective observational study was conducted on all patients with CO poisoning admitted to the emergency department of a tertiary hospital from 2016 to 2019. We followed-up patients to determine whether symptoms of DNS occurred at ≤6 months. We matched the propensity score to an equivalent distribution of potential covariates. RESULTS: A total of 224 patients with CO poisoning were enrolled in this study. NBO was used for 26 patients and HBO for 198 patients. DNS occurred in 40 patients. There were significant differences between the NBO and HBO groups in terms of carboxyhemoglobin, loss of consciousness, dizziness, chest pain, hospitalization, and length of hospital stay. The incidence of DNS was 19.2% in the HBO group, which was higher than the 7.7% observed in the NBO group, but the difference was not significant (p = 0.18). After propensity score matching, the incidence of DNS did not differ between the NBO and HBO groups (8.3% vs. 10.4%, p > 0.99). CONCLUSION: There was no difference in the incidence of DNS between groups receiving HBO and NBO in acute CO intoxication.

Synthesis and Single-Particle Surface-Enhanced Raman Scattering Study of Plasmonic Tripod Nanoframes with Y-Shaped Hot-Zones.

Herein, plasmonic metal tripod nanoframes with three-fold symmetry were synthesized in a high yield (∼83%), and their electric field distribution and single-particle surface-enhanced Raman scattering (SERS) were studied. We realized such complex frame morphology by synthesizing analogous tripod nanoframes through multiple transformations. The precise control of the Au growth pattern led to uniform tripod nanoframes embedded with circle or line-shaped hot spots. The linear-shaped nanogaps ("Y"-shaped hot-zone) of the frame structures can strongly and efficiently confine the electric field, allowing for strong SERS signals. Coupled with a high synthetic yield of the targeted frame structure, strong and uniform SERS signals were obtained inside the nanoframe gaps. Remarkably, quite reproducible SERS signals were obtained with these structures-the SERS enhancement factors with an average value of 7.9 × 107 with a distribution of enhancement factors from 2.2 × 107 to 2.2 × 108 for 45 measured individual particles.

Neurological symptoms improved by hyperbaric oxygen therapy in a post-cardiac arrest patient due to carbon monoxide poisoning: a case report.

Background: Carbon monoxide (CO) poisoning and cardiac arrest can cause neurological complications such as mental deterioration and movement disorders through ischemic brain injury. We report a case in which neurological sequelae after cardiac arrest caused by CO poisoning improved after hyperbaric oxygen (HBO2) therapy. Case report: A 43-year-old male visited the hospital with cardiac arrest due to CO poisoning. He developed neurological sequelae including mental deterioration and myoclonus after recovering spontaneous circulation. Anticonvulsant therapy was used after target temperature management but did not have a positive effect on neurological symptoms. However, after HBO2 therapy the patient's neurological symptoms improved, and he was discharged a month later. Conclusion: HBO2 therapy may be considered when neurological sequelae persist after cardiac arrest due to CO poisoning.

Silver Double Nanorings with Circular Hot Zone.

Silver double nanorings with circular intra-nanogaps between two nanorings of different diameters were synthesized without a linker molecule to confine an incident electromagnetic field in a single entity. We used on-demand, rational, and systematic multi-stepwise reactions consisting of (1) selective etching of gold, (2) rim-on deposition of platinum, (3) eccentric growth of gold, and (4) concentric growth of silver. The resulting silver double nanorings exhibited a high degree of homogeneity in both shape and size, with strongly coupled circular hot zones (or "hot halos", referring to the circular intra-nanogaps capable of focusing the near electromagnetic field) resulting from strong surface plasmon coupling between the inner and outer nanorings. Remarkably, these silver double nanorings exhibited strong, stable, and reproducible single-particle surface-enhanced Raman scattering signals without blinking. The signals appeared independently of polarization directions, which is a unique feature of a circular hot halo. The estimated enhancement factor was between 2 × 108 and 7 × 108. The measured limit of detection was 10-7 M in bulk concentration, and the signal appeared 570 s after sample exposure.

Quantitative Surface-Enhanced Raman Spectroscopy Analysis through 3D Superlattice Arrays of Au Nanoframes with Attomolar Detection.

This paper reports a methodology for synthesizing and ordering gold nanoframes into three-dimensional (3D) arrays with a controlled thickness, leading to homogeneous plasmonic superstructures, with which quantitative analysis via surface-enhanced Raman spectroscopy (SERS) has been successfully demonstrated. Because this preparation method allows for systematic control of nanoframe film thickness and the resulting 3D plasmonic superstructure, which exhibits a unique nanoporous network of hot-spots, detection limits down to 10-18 M, corresponding to ≈6000 molecules, have been measured. Compared to analogous solid nanoparticle superstructures, the nanoframe superstructures with their unique nanoporous architecture effectively dissipate the heat inevitably generated by laser excitation during measurement, effectively suppressing the formation of carbonaceous materials and therefore their accompanying fluorescence interference, especially important for low concentration detection.

The difference of subcutaneous digital nerve block method efficacy according to injection location.

INTRODUCTION: Finger injuries are commonly attended to in the emergency department, and digital nerve block is a frequently performed procedure for such injuries. This study compared the efficacy levels of the subcutaneous method according to the different injection sites. METHOD: This was a simulation study for medical students who rendered medical service at the emergency department. One group performed subcutaneous injection of lidocaine at the volar side of the metacarpophalangeal (MCP) joint, while another group injected at the volar side of the proximal interphalangeal (PIP) joint. The time to anesthesia was measured at 30-s intervals. Pain at the injection site was measured using the numeric rating scale (NRS), while the length from the fingertip to the injection site and the circumference of the injection site were measured. RESULTS: A total of 82 participants were included, with 41 under the MCP joint group and the rest under the PIP joint group. The mean length from the fingertip to the needling point was 3.62 ±â€¯0.63 cm in the PIP joint group and 5.90 ±â€¯0.65 cm in the MCP joint group, while the mean circumference of the needling point was 4.93 ±â€¯0.51 and 5.61 ±â€¯0.58 cm, and the mean time to anesthesia was 2.55 ±â€¯1.11 and 3.79 ±â€¯1.28 min (p-value < 0.001), respectively. The median value of NRS was 4 in both groups (p-value = 0.921). Length was correlated with the time to anesthesia (p-value = 0.018). CONCLUSION: Injection into the PIP joint showed the same anesthetic effect as injection into the MCP joint, but this effect occurred faster in the former.

Tracheal Irrigation Without Bronchoscopy as an Alternative Emergent Treatment of Blood Aspiration.

BACKGROUND: Tracheobronchial foreign body aspiration can cause mild symptoms but may also become dangerous enough to cause death. Bronchoscopy is the first choice for the diagnosis and the removal of aspirated foreign bodies. So, when bronchoscopy is not available, the situation might get challenging. CASE REPORT: A 62-year-old man was waiting for emergent surgery for traumatic epidural hematoma in the Emergency Department (ED). Endotracheal intubation was performed for surgery and airway maintenance. However, oxygen saturation dropped and respiratory arrest was expected. As emergent bronchoscopy could not be performed, the emergency physician decided to irrigate the trachea by using 0.9% normal saline in the ED. After three rounds of irrigation, vital signs including oxygen saturation improved and the patient could undergo neurosurgical surgery. The patient was subsequently discharged with improved health. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Bronchoscopy is the first choice for the treatment and diagnosis in cases of bronchial aspiration of blood, such as that caused by epistaxis. However, in emergency situations, such as deteriorating vital signs due to aspiration of life-threatening amounts of blood from epistaxis, using blind tracheal irrigation as an alternative tool when bronchoscopy is not available can help in achieving clinically acceptable results.

Drug Discovery Targeting the Disorder-To-Order Transition Regions through the Conformational Diversity Mimicking and Statistical Analysis.

Intrinsically disordered proteins exist as highly dynamic conformational ensembles of diverse forms. However, the majority of virtual screening only focuses on proteins with defined structures. This means that computer-aided drug discovery is restricted. As a breakthrough, understanding the structural characteristics of intrinsically disordered proteins and its application can open the gate for unrestricted drug discovery. First, we segmented the target disorder-to-order transition region into a series of overlapping 20-amino-acid-long peptides. Folding prediction generated diverse conformations of these peptides. Next, we applied molecular docking, new evaluation score function, and statistical analysis. This approach successfully distinguished known compounds and their corresponding binding regions. Especially, Myc proto-oncogene protein (MYC) inhibitor 10058F4 was well distinguished from others of the chemical compound library. We also studied differences between the two Methyl-CpG-binding domain protein 2 (MBD2) inhibitors (ABA (2-amino-N-[[(3S)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]-acetamide) and APC ((R)-(3-(2-Amino-acetylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester))). Both compounds bind MBD2 through electrostatic interaction behind its p66α-binding site. ABA is also able to bind p66α through electrostatic interaction behind its MBD2-binding site while APC-p66α binding was nonspecific. Therefore, structural heterogeneity mimicking of the disorder-to-order transition region at the peptide level and utilization of the new docking score function represent a useful approach that can efficiently discriminate compounds for expanded virtual screening toward intrinsically disordered proteins.

Physician Confidence in Artificial Intelligence: An Online Mobile Survey.

BACKGROUND: It is expected that artificial intelligence (AI) will be used extensively in the medical field in the future. OBJECTIVE: The purpose of this study is to investigate the awareness of AI among Korean doctors and to assess physicians' attitudes toward the medical application of AI. METHODS: We conducted an online survey composed of 11 closed-ended questions using Google Forms. The survey consisted of questions regarding the recognition of and attitudes toward AI, the development direction of AI in medicine, and the possible risks of using AI in the medical field. RESULTS: A total of 669 participants completed the survey. Only 40 (5.9%) answered that they had good familiarity with AI. However, most participants considered AI useful in the medical field (558/669, 83.4% agreement). The advantage of using AI was seen as the ability to analyze vast amounts of high-quality, clinically relevant data in real time. Respondents agreed that the area of medicine in which AI would be most useful is disease diagnosis (558/669, 83.4% agreement). One possible problem cited by the participants was that AI would not be able to assist in unexpected situations owing to inadequate information (196/669, 29.3%). Less than half of the participants(294/669, 43.9%) agreed that AI is diagnostically superior to human doctors. Only 237 (35.4%) answered that they agreed that AI could replace them in their jobs. CONCLUSIONS: This study suggests that Korean doctors and medical students have favorable attitudes toward AI in the medical field. The majority of physicians surveyed believed that AI will not replace their roles in the future.

Hepatic FXR/SHP axis modulates systemic glucose and fatty acid homeostasis in aged mice.

The nuclear receptors farnesoid X receptor (FXR; NR1H4) and small heterodimer partner (SHP; NR0B2) play crucial roles in bile acid homeostasis. Global double knockout of FXR and SHP signaling (DKO) causes severe cholestasis and liver injury at early ages. Here, we report an unexpected beneficial impact on glucose and fatty acid metabolism in aged DKO mice, which show suppressed body weight gain and adiposity when maintained on normal chow. This phenotype was not observed in single Fxr or Shp knockouts. Liver-specific Fxr/Shp double knockout mice fully phenocopied the DKO mice, with lower hepatic triglyceride accumulation, improved glucose/insulin tolerance, and accelerated fatty acid use. In both DKO and liver-specific Fxr/Shp double knockout livers, these metabolic phenotypes were associated with altered expression of fatty acid metabolism and autophagy-machinery genes. Loss of the hepatic FXR/SHP axis reprogrammed white and brown adipose tissue gene expression to boost fatty acid usage. CONCLUSION: Combined deletion of the hepatic FXR/SHP axis improves glucose/fatty acid homeostasis in aged mice, reversing the aging phenotype of body weight gain, increased adiposity, and glucose/insulin tolerance, suggesting a central role of this axis in whole-body energy homeostasis. (Hepatology 2017;66:498-509).

Liver receptor homolog-1 is a critical determinant of methyl-pool metabolism.

UNLABELLED: Balance of labile methyl groups (choline, methionine, betaine, and folate) is important for normal liver function. Quantitatively, a significant use of labile methyl groups is in the production of phosphatidylcholines (PCs), which are ligands for the nuclear liver receptor homolog-1 (LRH-1). We studied the role of LRH-1 in methyl-pool homeostasis and determined its metabolic effects using the methionine and choline-deficient (MCD) diet, which depletes methyl groups and results in a deleterious decrease in the PC-to-phosphatidylethanolamine ratio. We found that MCD diet-fed, liver-specific LRH-1 knockout mice (Lrh-1(-/-) ) do not show the expected decreased methyl-pool and PC/phosphatidylethanolamine ratio and are resistant to the hepatitis and fibrosis normally induced by the diet. Adaptive responses observed in wild-type mice on the MCD diet were also observed in Lrh-1(-/-) mice on a normal diet. This includes reduced expression of the highly active glycine-n-methyltransferase and the biliary phospholipid floppase multidrug-resistance protein 2 (Mdr2/Abcb4), resulting in reduced consumption of methyl groups and biliary PC secretion. In vitro studies confirm that Gnmt and Mdr2 are primary LRH-1 target genes. Additional similarities between hepatic gene expression profiles in MCD diet-fed wild-type and untreated Lrh-1(-/-) mice suggest that methyl-pool deficiency decreases LRH-1 activity, and this was confirmed by in vitro functional results in cells maintained in MCD medium. CONCLUSION: LRH-1 is a novel transcriptional regulator of methyl-pool balance; when the methyl-pool is depleted, decreased LRH-1 transactivation suppresses expression of key genes to minimize loss of labile methyl groups. (Hepatology 2016;63:95-106).

Highly improved reliability of amber light emitting diode with Ca -α-SiAlON phosphor in glass formed by gas pressure sintering for automotive applications.

Phosphor in glass (PiG) with 40 wt% of Ca-α-SiAlON phosphor and 60 wt% of Pb-free silicate glass was synthesized and mounted on a high-power blue LED to make an amber LED for automotive applications. Gas pressure sintering was applied after the conventional sintering process was used to achieve fully dense PiG plates. Changes in photoluminescence spectra and color coordination were inspected by varying the thickness of the plates that were mounted after optical polishing and machining. A trade-off between luminous flux and color purity was observed. The commercial feasibility of amber PiG packaged LED, which can satisfy international regulations for automotive components, was successfully demonstrated by examining the practical reliability under 85% humidity at an 85°C condition.