HIGH PLOIDY2-mediated SUMOylation of transcription factor ARR1 controls two-component signaling in Arabidopsis.

Cytokinins regulate plant growth, development, and responses to environmental stresses such as cold via phosphorelay from cytokinin receptors to the ARABIDOPSIS RESPONSE REGULATORs (ARRs). However, the molecular mechanisms underlying the activation of type-B ARR transcriptional activity in Arabidopsis (Arabidopsis thaliana) remain unclear. Here, we show that the E3 SUMO ligase HIGH PLOIDY2 SUMOylates ARR1, a type-B ARR, at K236, triggering its activation. Cold- or cytokinin-induced phosphorylation of ARR1 at D89 is crucial for its interaction with HPY2. Lysine 236 is critical for ARR1's transactivation without compromising its DNA-binding ability, while D89 is crucial for ARR1's binding to target gene promoters. Cytokinin enhances ARR1's chromatin binding, but cold does not. ARR1 K236 plays a critical role in promoting histone H3 acetylation in response to both cytokinin and cold without affecting chromatin binding. The K236R mutation in ARR1 reduces target gene expression and alters cytokinin and cold response phenotypes. This study unveils a mechanism of ARR1 activation wherein phosphorylated ARR1 interacts with HPY2 and binds to chromatin in response to cytokinin. Cold triggers a phosphorelay targeting chromatin-bound ARR1. HPY2 then catalyzes ARR1 SUMOylation at K236, enhancing histone H3 acetylation and leading to transcriptional activation of ARR1 in response to both cold and cytokinin.

Lung transplantation in pulmonary sarcoidosis.

Sarcoidosis is a systemic inflammatory disease of unknown etiology and variable clinical course. Pulmonary sarcoidosis is the most common presentation and accounts for most morbidity and mortality related to sarcoidosis. While sarcoidosis generally has good outcomes, few patients experience chronic disease. A minority of patients progress to a specific phenotype of sarcoidosis referred to advanced pulmonary sarcoidosis (APS) which includes advanced fibrosis, pulmonary hypertension and respiratory failure, leading to high morbidity and mortality. In patients with advanced disease despite medical therapy, lung transplantation may be the last viable option for improvement in quality of life. Though post-transplant survival is similar to that of other end-stage lung diseases, it is imperative that patients are evaluated and referred early to transplant centers with experience in APS. A multidisciplinary approach and clinical experience are crucial in detecting the optimal timing of referral, initiating comprehensive transplantation evaluation and listing, discussing surgical approach, and managing perioperative and post-transplant care. This review article seeks to address these aspects of lung transplantation in APS.

ROOT MERISTEM GROWTH FACTOR1 (RGF1)-RGF1 INSENSITIVE 1 peptide-receptor pair inhibits lateral root development via the MPK6-PUCHI module in Arabidopsis.

ROOT MERISTEM GROWTH FACTOR1 (RGF1) and its receptors RGF1 INSENSITIVEs (RGIs) regulate primary root meristem activity via a mitogen-activated protein kinase (MPK) signaling cascade in Arabidopsis. However, it is unknown how RGF1 regulates lateral root (LR) development. Here, we show that the RGF1-RGI1 peptide-receptor pair negatively regulates LR development via activation of PUCHI encoding AP2/EREBP. Exogenous RGF1 peptides inhibited LR development of the wild type. However, the rgi1 mutants were partially or fully insensitive to RGF1 during LR development, whereas four other rgi single mutants, namely rgi2, rgi3, rgi4, and rgi5, were sensitive to RGF1 in inhibiting LR formation. Consistent with this, the red fluorescent protein (RFP) signals driven by the RGF1 promoter were detected at stage I and the following stages, overlapping with RGI1 expression. PUCHI expression was significantly up-regulated by RGF1 but completely inhibited in rgi1. LR development of puchi1-1 was insensitive to RGF1. PUCHI expression driven by the RGI1 promoter reduced LR density in both the wild type and rgi1,2,3. Further, mpk6, but not mpk3, displayed significantly down-regulated PUCHI expression and insensitive LR development in response to RGF1. Collectively, these results suggest that the RGF1-RGI1 module negatively regulates LR development by activating PUCHI expression via MPK6.

Effect of dexamethasone and ramosetron on the prevention of postoperative nausea and vomiting in low-risk patients: a randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND: Several studies have investigated the effect of antiemetics on postoperative nausea and vomiting (PONV) in high-risk groups. However, few studies have investigated the effect of antiemetics in patients at low risk of developing PONV. METHODS: In this prospective, randomized, double-blinded trial, 177 patients undergoing surgery under general anesthesia were randomly allocated to three groups. Patients allocated to group C (control group) received 2 mL of intravenous 0.9% saline, those allocated to group R (ramosetron group) received 0.3 mg of intravenous ramosetron, and those allocated to group DR (ramosetron plus dexamethasone group) received 5 mg of intravenous dexamethasone and 0.3 mg of intravenous ramosetron. RESULTS: Finally, 174 patients completed the study, and the types of surgeries were orthopedic (n = 80), rhinologic (n = 47), urologic (n = 29), and others (n = 18). The incidence of PONV up to 48 h postoperatively was significantly lower in group DR than in group C. The incidence of PONV up to 0-1 h postoperatively was significantly lower in groups R and DR than in group C. The usage pattern of rescue antiemetics was consistent with the incidence of PONV. The percentage of patients requiring rescue analgesics 0-1 h postoperatively was significantly lower in groups R and DR than in group C. CONCLUSIONS: The combination of dexamethasone and ramosetron demonstrated a superior effect in preventing PONV for 48 h after surgery under general anesthesia than saline in patients at low risk of developing PONV. Compared with saline injections, ramosetron injections yielded better outcomes for the incidence of PONV and the use of rescue antiemetics and rescue analgesics 0-1 h postoperatively. TRIAL REGISTRATION: Clinical trial registration number: criskorea@korea.kr, KCT0006749.

Children's experiences of intravenous injection using the draw, write, and tell method: A mixed-methods study.

PURPOSES: This study aimed to explore children's perceptions and experiences of receiving intravenous (IV) injections and the self-reported pain scores and management strategies that can support children while receiving IV injections. DESIGN AND METHODS: This mixed-methods study included 17 children aged 4-11 years who presented to the outpatient clinic of a pediatric hospital and received IV injections. Data were collected using the draw, write, and tell method (DWT) and Facial Pain Rating Scale. Descriptive statistics and content analyses were performed. RESULTS: The children's self-reported mean pain score was 4.82, indicating moderate pain. Many expressions indicated that IV injections were painful or caused tingling or stinging sensations. A vague fear of needles in addition to pain was identified after listening to the children and analyzing their own interpretation of drawings. Three main themes were identified: (1) physical and emotional experiences, (2) parents as my secure base, and (3) comfort and relief strategies. CONCLUSIONS: Children expressed their experiences during IV injections, the alleviation of their pain and fear, and their suggestions for comfort and relief strategies visually, auditorily, and verbally. Parents played an important role in supporting their children and reducing pain, anxiety, and distress related to the IV procedure. PRACTICE IMPLICATIONS: The DWT, as an arts-based and child-centered approach, is a useful and valid method to understand children's experience related to the IV injection. Children experience comfort and relief within a family-centered care context during IV injection. Nurses should promote children's and parents' participation in the development of strategies to reduce the negative effects of IV injections in children.

Color gamut change by optical crosstalk in high-resolution organic light-emitting diode microdisplays.

Herein, the color gamut change by optical crosstalk between sub-pixels in high-resolution full-color organic light-emitting diode (OLED) microdisplays was numerically investigated. The color gamut of the OLED microdisplay decreased dramatically as the pixel density of the panel increased from 100 pixels per inch (PPI) to 3000 PPI. In addition, the increase in thickness of the passivation layer between the bottom electrode and the top color filter results in a decrease in the color gamut. We also calculated the color gamut change depending on the pixel structures in the practical OLED microdisplay panel, which had an aspect ratio of 32:9 and a pixel density of 2,490 PPI. The fence angle and height, refractive index of the passivation layer, black matrix width, and white OLED device structure affect the color gamut of the OLED microdisplay panel because of the optical crosstalk effect.

Optimal initial diet in mild acute pancreatitis: A comprehensive meta-analysis of randomized control trials.

OBJECTIVE: We performed a comprehensive systematic review and meta-analysis comparing initiation of full solid diet (FSD) versus stepwise diet to better define the management of patients with mild acute pancreatitis (AP). METHODS: Electronic databases were searched through August 2, 2021 for trials comparing initial FSD versus stepwise advancement in patients with mild AP on length of hospital stay (LOHS). We stratified by whether diet was initiated early (within 24 h or immediately upon presence of bowel sounds). RESULTS: We identified seven RCTs that compared LOHS in AP patients who received initial oral intake with solid diet versus stepwise diet. Across the studies a total of 305 patients were randomized to immediate FSD and 308 patients to sequential advancement. Patients who were initiated on a FSD had a significant reduction in total LOHS (Standardized Mean Difference (SMD) -0.52 [95% CI -0.69, -0.36]). There was no difference in post refeeding abdominal pain, tolerance of diet, or necessity to cease diet between the two groups. Sub-analysis of three studies that initiated FSD early reduced total LOHS (OR -0.95 [95% CI -1.26, -0.65]) compared to those who received graded diet advancement as well as higher likelihood of tolerating the assigned diet (OR 6.8 [95% CI 1.2, 39.2]). CONCLUSIONS: Our meta-analysis shows that initiation of FSD reduces total LOHS in patients with mild AP and does not increase post refeeding abdominal pain. Though additional high-quality studies are needed, these findings support initial solid diet for AP and consideration of feeding within the first 24 h.

The Roles and Associated Mechanisms of Adipokines in Development of Metabolic Syndrome.

Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.

Impact of water consumption on renal function in the general population: a cross-sectional analysis of KNHANES data (2008-2017).

BACKGROUND: The renoprotective effect of water intake remains unclear. We aimed to investigate the relationship between water intake and renal impairment in the Korean general population, focusing on individual differences in body fluid distribution and risk of chronic dehydration. METHODS: We conducted a cross-sectional analysis of the 2008-2017 Korea National Health and Nutrition Examination Survey (KNHANES). Adult participants who had body weight and serum creatinine data and had answered 24-h recall nutritional survey were included. Four water intake groups were defined by daily total water intake per body weight: lowest (< 20 mL/kg/day), low-moderate (20-29.9 mL/kg/day), high-moderate (30-49.9 mL/kg/day), and highest (≥ 50 mL/kg/day). We assessed the risk of renal impairment (estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2) according to water intake. RESULTS: In total of 50,113 participants, 3.9% had renal impairment. The risk of renal impairment gradually decreased as water intake increased. After adjustment of sodium intake, the trend of renoprotective effect was remained in low-moderate and high-moderate water intake group compared to low intake group, whereas no significant impact was observed with the highest water intake due to concurrent intake of high sodium. In subgroup analysis, the renoprotective effect of water intake was significant in the participants with elderly, male and daily sodium intake over 2 g/day. CONCLUSIONS: High daily water intake is renoprotective. Our data may provide an important basis for determining the amount of water intake needed to prevent renal impairment, considering variations in body weight, body composition and risk of chronic dehydration.

Effectiveness of one-on-one coaching in improving pressurized metered dose inhaler (pMDI) technique among COPD patients: a prospective clinical study.

BACKGROUND: Incorrect use of inhalers among asthma and COPD patients is very prevalent. Yet, no single intervention is considered standard of care. We aimed to conduct a COPD-specific investigation of active one-on-one coaching as the educational intervention to improve pressurized metered dose inhaler (pMDI) technique and COPD symptoms management. METHODS: COPD patients who have pMDI in their treatment regimen were enrolled in this prospective study using the Global Initiative for Chronic Obstructive Lung Disease criteria. After rapid cognitive screen, inhaler technique was assessed and an active one-on-one coaching was provided utilizing the 12-step American Thoracic Society instructions. Patients' inhaler technique was assessed and scored again at their regular follow-up visits. RESULTS: One hundred and one patients participated in the study. The percentage of pMDI misuse decreased from 43.5% pre-teaching to 12.9% post-teaching (binomial test p value < 0.001). The mean number of errors decreased from 3.1 errors pre-teaching to 1.7 errors post-teaching (paired t-test p value < 0.001). The number needed to treat was 3.3 patients to prevent one misuse. Patients with an impaired cognitive function were more likely to have inhaler misuse in general and less likely to improve their technique when provided training. CONCLUSIONS: This study reveals that many COPD patients have incorrect pMDI techniques that can be improved with a short training in the clinic. TRIAL REGISTRATION: Not applicable.

Pediatric Postoperative Pain Management in Korea: Parental Attitudes Toward Pain and Analgesics, Self-Efficacy, and Pain Management.

PURPOSES: This study aimed to explore parental attitudes toward children's pain and analgesic drugs and parental self-efficacy and use of pain relief strategies in children's postoperative pain management in Korea, and to identify the relationships among these variables. DESIGN AND METHODS: A cross sectional descriptive study was conducted. Participants were 124 parents of hospitalized children (aged 4-9 years) undergoing tonsillectomy in Korea. RESULTS: A considerable proportion of parents held misconceptions about how children express pain. For example, 87.9% of parents perceived that children always tell their parents when they are in pain. Moreover, parents reported significant attitudinal barriers to analgesic use with 60.5% of parents believed that side effects are something to worry about when giving children pain medication. Parental attitudes to use analgesics were significantly different by children's gender, family income, and length of hospital stay. Emotional support methods such as touch, parental presence, and comfort/reassurance were the frequently used, whereas cognitive-behavioral approaches such as distraction were less frequently used nonpharmacological pain relief strategies. A parent's self-efficacy in managing children's pain significantly correlated with the appropriate use of analgesics and parental use of pain relief strategies. CONCLUSIONS: Promoting parental self-efficacy in postoperative pain management is important. Educational interventions focused on behavioral changes of parents, including practical guidance for pharmacological and nonpharmacological pain relief strategies, are needed. PRACTICE IMPLICATIONS: Providing parents with proper, effective education about children's postoperative pain management should not only provide accurate information but should also enhance parents' self-efficacy in assessing and managing children's pain.

Comparison of General and Spinal Anaesthesia on Systemic Inflammatory Response in Patients Undergoing Total Knee Arthroplasty: A Propensity Score Matching Analysis.

Background and Objectives: Some of the postoperative complications following orthopaedic surgeries are associated with a systemic inflammatory response (SIR), which varies depending on the anaesthetic technique. We aimed to compare the effects of general and spinal anaesthesia on the SIR after total knee arthroplasty (TKA), based on C-reactive protein (CRP) levels, the platelet-lymphocyte ratio (PLR), and the neutrophil-lymphocyte ratio (NLR). Materials and Methods: Patients who underwent TKA between January 2014 and December 2018 were included. Electronic medical records of the patients were retrospectively reviewed and analysed. To reduce the impact of potential confounding factors, we performed propensity score matching according to the anaesthetic technique. Results: A total of 1311 TKA cases were analysed. After propensity score matching, the maximal CRP value and changes in CRP levels in the general anaesthesia group were higher than those in the spinal anaesthesia group. However, the maximal NLR and PLR and the changes in NLR and PLR were not different between the two groups. There were no differences in postoperative clinical outcomes. Conclusion: Spinal anaesthesia tended to induce a lower inflammatory response than general anaesthesia when considering CRP levels in patients undergoing TKA. However, the effects of anaesthetic techniques on the overall outcomes were not significant.

Effects of hyperthermia on the effective concentration of rocuronium and sugammadex-mediated reversal in isolated phrenic nerve hemidiaphragm preparations of rats.

BACKGROUND: Hyperthermia is relatively rare during general anesthesia; however, a few studies have been conducted on hyperthermia and the neuromuscular blockade (NMB) induced by rocuronium, and the reversal of NMB by sugammadex. We investigated the effect of hyperthermia status on the NMB induced by rocuronium, and its reversal by sugammadex, in isolated phrenic nerve hemidiaphragm (PNHD) preparations of the rat. METHODS: Thirty-three male Sprague-Dawley rat PNHD preparations were randomly assigned to three groups at different temperatures (36 °C, 38 °C, and 40 °C; each group, n = 11, in Krebs solution). The train-of-four (TOF) and twitch height responses were checked mechanomyographically. The PNHD were treated with progressively increasing doses of rocuronium and three effective concentrations (ECs), EC50, EC90, and EC95, of rocuronium were analyzed in each group via nonlinear regression analysis. Then, sugammadex was administered in doses equimolar to rocuronium. Thereafter, the T1 height (%), TOFR (%) and the duration index were measured. RESULTS: The EC of rocuronium (EC50, EC90, and EC95) decreased significantly in accordance with increasing temperature. The groups at 36 °C and 40 °C showed clear differences in all areas (all P < 0.001). Moreover, the T1 height (%) and the duration index upon sugammadex administration showed faster recovery results in the36 °C than the 38 °C and 40 °C groups. CONCLUSION: A rise of temperature from 38 °C to 40 °C in rat PNHD preparations proportionally enhanced the NMB induced by rocuronium. In addition, equimolar doses of sugammadex to the administered rocuronium showed a slower recovery time as the temperature rises.

Targeting ß-catenin overcomes MEK inhibition resistance in colon cancer with KRAS and PIK3CA mutations.

BACKGROUND: Mitogen-activated protein kinases (MEK 1/2) are central components of the RAS signalling pathway and are attractive targets for cancer therapy. These agents continue to be investigated in KRAS mutant colon cancer but are met with significant resistance. Clinical investigations have demonstrated that these strategies are not well tolerated by patients. METHODS: We investigated a biomarker of response for MEK inhibition in KRAS mutant colon cancers by LC-MS/MS analysis. We tested the MEK inhibitor in PIK3CA wild(wt) and mutant(mt) colon cancer cells. In addition, we tested the combinational effects of MEK and TNKS inhibitor in vitro and in vivo. RESULTS: We identified ß-catenin, a key mediator of the WNT pathway, in response to MEK inhibitor. MEK inhibition led to a decrease in ß-catenin in PIK3CA wt colon cancer cells but not in mt. Tumour regression was promoted by combination of MEK inhibition and NVP-TNS656, which targets the WNT pathway. Furthermore, inhibition of MEK promoted tumour regression in colon cancer patient-derived xenograft models expressing PIK3CA wt. CONCLUSIONS: We propose that inhibition of the WNT pathway, particularly ß-catenin, may bypass resistance to MEK inhibition in human PIK3CA mt colon cancer. Therefore, we suggest that ß-catenin is a potential predictive marker of MEK inhibitor resistance.

Asynchronous Alterations of Muscle Force and Tendon Stiffness Following 8 Weeks of Resistance Exercise with Whole-Body Vibration in Older Women.

This study aimed to examine whether muscle force and tendon stiffness in a muscle-tendon complex alter synchronously following 8-week whole-body vibration (WBV) training in older people. Forty older women aged 65 years and older were randomly assigned into control (CON, n = 15) and whole-body vibration (WBV) training groups (exposure time, n = 13; vibration intensity, n = 12). For the training groups, a 4-week detraining period was completed following the training period. Throughout the training/detraining period, force of the medial gastrocnemius (MG) muscle and stiffness of the Achilles tendon were assessed four times (0, 4, 8, and 12 weeks) using a combined system of dynamometer and ultrasonography. While muscle force gradually increased throughout the training period (p < .05), a significant increase in tendon stiffness was observed after 8 weeks (p < .05). These findings indicated that, during the early phase of WBV training, muscle force and tendon stiffness changed asynchronously, which might be a factor in possible musculotendinous injuries.

Cellular Localization of Wheat High Molecular Weight Glutenin Subunits in Transgenic Rice Grain.

Rice (Oryza sativa L.) is a primary global food cereal. However, when compared to wheat, rice has poor food processing qualities. Dough that is made from rice flour has low viscoelasticity because rice seed lacks storage proteins that are comparable to gluten protein from wheat. Thus, current research efforts aim to improve rice flour processing qualities through the transgenic expression of viscoelastic proteins in rice seeds. In this study, we characterized the transgenic expression of wheat glutenin subunits in rice seeds. The two genes 1Dx5_KK and 1Dy10_JK, which both encode wheat high-molecular-weight glutenin subunits that confer high dough elasticity, were cloned from Korean wheat cultivars KeumKang and JoKyung, respectively. These genes were inserted into binary vectors under the control of the rice endosperm-specific Glu-B1 promoter and were expressed in the high-amylose Korean rice cultivar Koami (Oryza sativa L.). Individual expression of both glutenin subunits was confirmed by SDS-PAGE and immunoblot analyses performed using T3 generation of transgenic rice seeds. The subcellular localization of 1Dx5_KK and 1Dy10_JK in the rice seed endosperm was confirmed by immunofluorescence analysis, indicating that the wheat glutenin subunits accumulate in protein body-II and novel protein body types in the rice seed. These results contribute to our understanding of engineered seed storage proteins in rice.

Graphene mode-locked femtosecond Cr2+:ZnS laser with ~300 nm tuning range.

Graphene has proved to be an excellent broadband saturable absorber for mode-locked operation of ultrafast lasers. However, for the mid-infrared (mid-IR) range where broadly tunable sources are in great needs, graphene-based broadly tunable ultrafast mid-IR lasers have not been demonstrated so far. Here, we report on passive mode-locking of a mid-IR Cr:ZnS laser by utilizing a transmission-type monolayer graphene saturable absorber and broad spectral tunability between 2120 nm and 2408 nm, which is the broadest tuning bandwidth ever reported for graphene mode-locked mid-IR solid-state lasers. The recovery time of the saturable absorber is measured to be ~2.4 ps by pump-probe technique at a wavelength of 2350 nm. Stably mode-locked Cr:ZnS laser delivers Fourier transform-limited 220-fs pulses with a pulse energy of up to 7.8 nJ.

Hepatocellular carcinoma-targeted drug discovery through image-based phenotypic screening in co-cultures of HCC cells with hepatocytes.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide and is associated with substantial mortality. Because HCCs have strong resistance to conventional chemotherapeutic agents, novel therapeutic strategies are needed to improve survival in HCC patients. METHODS: Here, we developed a fluorescence image-based phenotypic screening system in vitro to identify HCC-specific drugs in co-cultures of HCC cells with hepatocytes. To this end, we identified two distinctive markers of HCC, CHALV1 and AFP, which are highly expressed in HCC cell lines and liver cancer patient-derived materials. We applied these markers to an HCC-specific drug screening system. RESULTS: Through pilot screening, we identified three anti-folate compounds that had HCC-specific cytotoxicity. Among them, pyrimethamine exhibited the greatest HCC-specific cytotoxicity. Interestingly, pyrimethamine significantly increased the size and number of lysosomes and subsequently induced the release of cathepsin B from the lysosome to the cytosol, which triggered caspase-3-dependent apoptosis in Huh7 (HCC) but not Fa2N-4 cells (immortalized hepatocytes). Importantly, Fa2N-4 cells had strong resistance to pyrimethamine relative to Huh7 cells in 2D and 3D culture systems. CONCLUSION: These results demonstrate that this in vitro image-based phenotypic screening platform has the potential to be widely adopted in drug discovery research, since we promptly estimated anticancer activity and hepatotoxicity and elucidated functional roles of pyrimethamine during the apoptosis process in HCC.

Effects of formaldehyde on mitochondrial dysfunction and apoptosis in SK-N-SH neuroblastoma cells.

Methanol ingestion is neurotoxic in humans due to its metabolites, formaldehyde and formic acid. Here, we compared the cytotoxicity of methanol and its metabolites on different types of cells. While methanol and formic acid did not affect the viability of the cells, formaldehyde (200-800 µg/mL) was strongly cytotoxic in all cell types tested. We investigated the effects of formaldehyde on oxidative stress, mitochondrial respiratory functions, and apoptosis on the sensitive neuronal SK-N-SH cells. Oxidative stress was induced after 2 h of formaldehyde exposure. Formaldehyde at a concentration of 400 µg/mL for 12 h of treatment greatly reduced cellular adenosine triphosphate (ATP) levels. Confocal microscopy indicated that the mitochondrial membrane potential (MMP) was dose-dependently reduced by formaldehyde. A marked and dose-dependent inhibition of mitochondrial respiratory enzymes, viz., NADH dehydrogenase (complex I), cytochrome c oxidase (complex IV), and oxidative stress-sensitive aconitase was also detected following treatment with formaldehyde. Furthermore, formaldehyde caused a concentration-dependent increase in nuclear fragmentation and in the activities of the apoptosis-initiator caspase-9 and apoptosis-effector caspase-3/-7, indicating apoptosis progression. Our data suggests that formaldehyde exerts strong cytotoxicity, at least in part, by inducing oxidative stress, mitochondrial dysfunction, and eventually apoptosis. Changes in mitochondrial respiratory function and oxidative stress by formaldehyde may therefore be critical in methanol-induced toxicity.

YAG Laser Membranotomy for Subinternal Limiting Membrane Hemorrhage.

PURPOSE: To report the use of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser internal limiting membranotomy to successfully treat the first reported case of subinternal limiting membrane (sub-ILM) hemorrhage that developed after coil embolization of a cerebral aneurysm. CASE REPORT: A 59-year-old Korean woman visited our clinic complaining of central scotoma in her left eye, which developed shortly after stent-assisted coil embolization of an unruptured internal carotid artery aneurysm. Fundus examination revealed a sub-ILM hemorrhage in her left eye, and after 2 days, a Nd:YAG laser membranotomy was performed with a single 4.5-mJ burst. There was a marked reduction in the sub-ILM hemorrhage 1 day after Nd:YAG laser membranotomy, and after 1 month, her best-corrected visual acuity improved to 20/20, with complete resolution of the sub-ILM hemorrhage. CONCLUSIONS: Sub-ILM hemorrhage can develop after coil embolization of a cerebral aneurysm, and Nd:YAG laser internal limiting membranotomy can be a useful noninvasive treatment alternative to surgical intervention.