Assessment of zinc, manganese, copper, and magnesium intake levels in Koreans using the Korean Total Diet Study.

This study evaluated zinc, manganese, copper, and magnesium intake levels in Koreans using the Korean Total Diet Study, targeting 92-93% of the Korean diet. Representative foods were collected from 9 cities, resulting in 1344-1368 samples. Results showed adequate intake for most minerals, but high proportions of adults and adolescents didn't meet recommended levels. Infants had high levels of zinc and manganese intake, posing possible health concerns. This is the first comprehensive assessment of these nutrients in Korea and is significant for considering all age groups, including infants, by analyzing nutrient content for table-ready (cooked) samples of foods. It is hoped that the Korean Total Diet Survey will be expanded to assess a wider range of nutrients for better nutrient intake assessment in Korea. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01394-y.

Survival Outcomes in Premenopausal Patients With Invasive Lobular Carcinoma.

Importance: The disparate prognostic implications between invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have been demonstrated. However, information on premenopausal patients remains insufficient. Objective: To examine long-term survival outcomes of ILC and IDC in premenopausal patients using national databases. Design, Setting, and Participants: This cohort study used the Surveillance, Epidemiology, and End Results (SEER), Korean Breast Cancer Registry (KBCR), and Asan Medical Center Research (AMCR) databases to identify premenopausal patients with stage I to III ILC or IDC between January 1, 1990, and December 31, 2015. The median follow-up time was 90 (IQR, 40-151) months in the SEER database, 94 (IQR, 65-131) months in the KBCR database, and 120 (IQR, 86-164) months in the AMCR database. Data were analyzed from January 1 to May 31, 2023. Main Outcomes and Measures: The primary outcome was breast cancer-specific survival (BCSS), which was analyzed according to histological type, and the annual hazard rate was evaluated. Survival rates were analyzed using a log-rank test and a Cox proportional hazards regression model with time-varying coefficients. Multivariable analysis was performed by adjusting for tumor characteristics and treatment factors. Results: A total of 225 938 women diagnosed with IDC or ILC and younger than 50 years were identified. Mean (SD) age at diagnosis was 42.7 (5.3) years in the SEER database, 41.8 (5.5) years in the KBCR database, and 41.8 (5.5) years in the AMCR database. In terms of race (available for the SEER database only), 12.4% of patients were Black, 76.1% were White, 11.0% were of other race (including American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander), and 0.5% were of unknown race). Patients with ILC had better BCSS in the first 10 years after diagnosis than those with IDC (hazard ratios [HRs], 0.73 [95% CI, 0.68-0.78] in the SEER database, 1.20 [95% CI, 0.91-1.58] in the KBCR database, and 0.50 [95% CI, 0.29-0.86] in the AMCR database), although BCSS was worse after year 10 (HRs, 1.80 [95% CI, 1.59-2.02] in the SEER database, 2.79 [95% CI, 1.32-5.88] in the KBCR database, and 2.23 [95% CI, 1.04-4.79] in the AMCR database). Similar trends were observed for hormone receptor-positive tumors (HRs, 1.55 [95% CI, 1.37-1.75] in the SEER database, 2.27 [95% CI, 1.01-5.10] in the KBCR database, and 2.12 [95% CI, 0.98-4.60] in the AMCR database). Considering the annual hazard model of BCSS, IDC events tended to decline steadily after peaking 5 years before diagnosis. However, the annual peak event of BCSS was observed 5 years after diagnosis for ILC, which subsequently remained constant. Conclusions and Relevance: These findings suggest that premenopausal women with ILC have worse BCSS estimates than those with IDC, which can be attributed to a higher late recurrence rate of ILC than that of IDC. Histological subtypes should be considered when determining the type and duration of endocrine therapy in premenopausal women.

Evaluating the effect of age on postoperative and clinical outcomes in patients admitted to the intensive care unit after gastrointestinal cancer surgery.

BACKGROUND: This study aimed to compare postoperative and clinical outcomes according to age and analyze the effect of age on mortality in patients admitted to the intensive care unit immediately after gastrointestinal cancer surgery. METHODS: A total of 477 patients admitted to the intensive care unit after gastrointestinal cancer surgery between March 2018, and February 2020, were classified into 3 groups according to age: young (<65 years), older (65-79 years), and oldest (≥80 years) groups. We compared their disease severity scores as well as postoperative and clinical outcomes including mortality. RESULTS: The young group comprised 167 (35.0%) patients, the older group 222 (46.5%) patients, and the oldest group 88 (18.4%) patients. There was a significant difference in the American Society of Anesthesiologists score, but not in the Acute Physiology and Chronic Health Evaluation II score, among the groups. The younger the age, the higher was the rate of vasopressor use; however, there were no significant differences in other postoperative and clinical outcomes, such as mechanical ventilation, length of hospital stay, length of intensive care unit stay, form of discharge, intensive care unit re-admission rate, in-hospital mortality, and in-30 days mortality. No significant differences in in-hospital survival, in-30 days survival, and overall survival were observed among the 3 groups. CONCLUSION: The comorbidities of patients increase with age; however, there was no significant difference in postoperative and clinical outcomes related to age. Thereby, the older population can successfully undergo major operations if adequate perioperative management is provided.

Systematic profiling of the chicken gut microbiome reveals dietary supplementation with antibiotics alters expression of multiple microbial pathways with minimal impact on community structure.

BACKGROUND: The emergence of antimicrobial resistance is a major threat to global health and has placed pressure on the livestock industry to eliminate the use of antibiotic growth promotants (AGPs) as feed additives. To mitigate their removal, efficacious alternatives are required. AGPs are thought to operate through modulating the gut microbiome to limit opportunities for colonization by pathogens, increase nutrient utilization, and reduce inflammation. However, little is known concerning the underlying mechanisms. Previous studies investigating the effects of AGPs on the poultry gut microbiome have largely focused on 16S rDNA surveys based on a single gastrointestinal (GI) site, diet, and/or timepoint, resulting in an inconsistent view of their impact on community composition. METHODS: In this study, we perform a systematic investigation of both the composition and function of the chicken gut microbiome, in response to AGPs. Birds were raised under two different diets and AGP treatments, and 16S rDNA surveys applied to six GI sites sampled at three key timepoints of the poultry life cycle. Functional investigations were performed through metatranscriptomics analyses and metabolomics. RESULTS: Our study reveals a more nuanced view of the impact of AGPs, dependent on age of bird, diet, and intestinal site sampled. Although AGPs have a limited impact on taxonomic abundances, they do appear to redefine influential taxa that may promote the exclusion of other taxa. Microbiome expression profiles further reveal a complex landscape in both the expression and taxonomic representation of multiple pathways including cell wall biogenesis, antimicrobial resistance, and several involved in energy, amino acid, and nucleotide metabolism. Many AGP-induced changes in metabolic enzyme expression likely serve to redirect metabolic flux with the potential to regulate bacterial growth or produce metabolites that impact the host. CONCLUSIONS: As alternative feed additives are developed to mimic the action of AGPs, our study highlights the need to ensure such alternatives result in functional changes that are consistent with site-, age-, and diet-associated taxa. The genes and pathways identified in this study are therefore expected to drive future studies, applying tools such as community-based metabolic modeling, focusing on the mechanistic impact of different dietary regimes on the microbiome. Consequently, the data generated in this study will be crucial for the development of next-generation feed additives targeting gut health and poultry production. Video Abstract.

Assessment of dietary exposure to heterocyclic amines based on the Korean total diet study.

Heterocyclic amines (HCAs) are contaminants in proteinaceous foods produced by cooking at high temperatures. This study was the first assessment of exposure to HCAs using the Korean total diet study. Twelve HCAs were analysed in 1,232 pooled samples using six isotope-labelled internal standards and HPLC-MS/MS. The daily intake of HCAs in the Korean population was estimated based on the concentration of HCAs in the total diet study samples and individual food consumption data from the Korean National Health and Nutrition Examination Survey. Among HCAs, the intake of ß-carbolines, such as harman and norharman, was the highest, followed by the intake of PhIP. The primary sources of HCA intake were meat, fish, shellfish, and beverages, including alcohol. The margin of exposure to PhIP was 2,349,000 at the average level and 373,000 at the 95th percentile in the Korean population. The estimated daily intake of all HCAs in the Korean population was considered safe.

First report of Colombian datura virus in Brugmansia suaveolens in Korea.

Brugmansia suaveolens, known as angel's trumpet, is a perennial ornamental shrub in the Solanaceae with large fragrant flowers. In June 2018, a leaf sample of B. suaveolens that showed virus-like symptoms including chlorotic spots, yellowing and mottle on leaves was collected from a greenhouse in Seongnam, South Korea for disease diagnosis (Supplementary Figure S1a, b). Disease incidence in the greenhouse was greater than 80% for about 2,000 B. suaveolens plants. To identify a causal virus, transmission electron microscopy (TEM) was used to analyze symptomatic leaf samples using leaf dips and thin section methods. Filamentous virus particles and pinwheel structures were observed, indicating the presence of a potyvirus (Supplementary Figure S1c, d). To confirm the TEM results, a symptomatic leaf sample was further analyzed by reverse-transcription polymerase chain reaction (RT-PCR) using species-specific detection primers for three potyviruses that infect Brugmansia spp.: Colombian datura virus (CDV), Brugmansia mosaic virus (BruMV), and Brugmansia suaveolens mottle virus (BsMoV) (Lucinda et al, 2008; Park et al., 2014; Verma et al., 2014). The sample was positive only for CDV. CDV is transmitted by aphids in a nonpersistent manner and mechanical inoculation and can infect plants in the Solanaceae family including tomato and tobacco (Kahn and Bartels 1968; Schubert et al. 2006; Verhoeven et al. 1996) and has been designated a quarantine virus in Korea. Additional analysis of 13 symptomatic B. suaveolens plants from the infected greenhouse found that all samples except one were infected with CDV. To isolate CDV from B. suaveolens, leaf extracts from symptomatic samples were mechanically inoculated on an assay host, Nicotiana tabacum cv. BY via three single-lesion passages followed by propagation in N. benthamiana. For the bioassay of the CDV isolate (CDV-AT-Kr), sap from infected N. benthamiana was mechanically inoculated on 31 indicator plants, including B. suaveolens (Supplementary Table S2). CDV-AT-Kr induced chlorotic local lesions, necrotic local lesions, mottle, and/or mosaic systemically in 10 Nicotiana spp., and mottle and yellowing in tomato. On inoculated B. suaveolens, te mild mottle symptom was reproduced. No symptoms were observed in pepper or Datura stramonium. These results were confirmed by RT-PCR. To characterize CDV-AT-Kr genetically, the complete genome sequence of CDV-AT-Kr was obtained by RT-PCR using specific primers (Supplementary Table S3) and deposited in GenBank (accession no. MW075268). The CDV-AT-Kr RNA consists of 9,620 nt, encoding a polyprotein of 3,076 aa. BLASTn analysis showed that CDV-AT had maximum nucleotide identities of 98.9% at the complete genome level with a CDV isolate (accession no. JQ801448) from N. tabacum in the UK. To our knowledge, this is the first report of CDV infection in B. suaveolens in Korea and the second report in the world of the complete genome sequence. As B. suaveolens is cultivated by vegetative propagation, production and maintenance of virus-free, healthy B. suaveolens is needed. In addition, as new CDV hosts have been repeatedly reported (Pacifico et al., 2016; Salamon et al., 2015; Tomitaka et al., 2014; Verma et al., 2014), we are monitoring nationwide occurrence to prevent the spread of the virus to other crops.

High-frequency Cochlear Nerve Deficit Region: Relationship With Deaf Duration and Cochlear Implantation Performance in Postlingual Deaf Adults.

OBJECTIVE: To analyze the changes of cochlear nerve diameter and the presence of a cochlear nerve deficit at a high-frequency region and investigate their effects on cochlear implant (CI) performance in postlingual deaf adults. STUDY DESIGN: Retrospective. SETTING: Tertiary care academic center. PATIENTS: Eighty-three postlingual deaf adults with no labyrinthine anomalies or cognitive deficits who received a CI with perimodiolar electrodes from a single manufacturer. MAIN OUTCOMES AND MEASURES: We evaluated the changes of cochlear nerve diameter and the presence of a "tail sign," defined as identifiable nerve fibers originating from the far basal turn of the cochlea, which represents the presence of cochlear nerve at a high-frequency region in magnetic resonance imaging, on monosyllabic word recognition scores. RESULTS: The cochlear nerve diameter showed a positive correlation with word recognition scores (maximum diameter, R2 = 0.26, p < 0.01; minimum diameter, R2 = 0.26, p < 0.01), but a negative correlation with deaf duration. Recipients with a positive tail sign performed better (73 ±â€Š19%) than those without (45 ±â€Š24%, p < 0.01). A positive tail sign was more commonly found in good performers (52 of 62, 84%) than in poor performers (5 of 21, 24%, p < 0.01). CONCLUSIONS: Favorable outcomes could be anticipated in postlingual deaf adults with a large cochlear nerve diameter and positive tail sign. A presence of cochlear nerve at a high-frequency region may be an imaging marker for predicting good CI performance.

Cortical reorganization following auditory deprivation predicts cochlear implant performance in postlingually deaf adults.

Long-term hearing loss in postlingually deaf (PD) adults may lead to brain structural changes that affect the outcomes of cochlear implantation. We studied 94 PD patients who underwent cochlear implantation and 37 patients who were MRI-scanned within 2 weeks after the onset of sudden hearing loss and expected with minimal brain structural changes in relation to deafness. Compared with those with sudden hearing loss, we found lower gray matter (GM) probabilities in bilateral thalami, superior, middle, inferior temporal cortices as well as the central cortical regions corresponding to the movement and sensation of the lips, tongue, and larynx in the PD group. Among these brain areas, the GM in the middle temporal cortex showed negative correlation with disease duration, whereas the other areas displayed positive correlations. Left superior, middle temporal cortical, and bilateral thalamic GMs were the most accurate predictors of post-cochlear implantation word recognition scores (mean absolute error [MAE] = 10.1, r = .82), which was superior to clinical variables used (MAE: 12.1, p < .05). Using the combined brain morphological and clinical features, we achieved the best prediction of the outcome (MAE: 8.51, r = .90). Our findings suggest that the cross-modal plasticity allowing the superior temporal cortex and thalamus to process other modal sensory inputs reverses the initially lower volume when deafness becomes persistent. The middle temporal cortex processing higher-level language comprehension shows persistent negative correlations with disease duration, suggesting this area's association with degraded speech comprehensions due to long-term deafness. Morphological features combined with clinical variables might play a key role in predicting outcomes of cochlear implantation.

Psychological Impact of Quarantine on Caregivers at a Children's Hospital for Contact with Case of COVID-19.

Quarantine often provokes negative psychological consequences. Thus, we aimed to identify the psychological and behavioral responses and stressors of caregivers quarantined with young patients after a close contact to a coronavirus disease 2019 case at a children's hospital. More than 90% of the caregivers reported feelings of worry and nervousness, while some of them reported suicidal ideations (4.2%), and/or homicidal ideations (1.4%). Fear of infection of the patient (91.7%) and/or oneself (86.1%) were most frequently reported stressors. A multidisciplinary team including infection control team, pediatrician, psychiatrist, nursing staff and legal department provided supplies and services to reduce caregiver's psychological distress. Psychotropic medication was needed in five (6.9%), one of whom was admitted to the psychiatry department due to suicidality. Quarantine at a children's hospital makes notable psychological impacts on the caregivers and a multidisciplinary approach is required.

Long-term Change in the Speech Perception Ability in Pediatric Cochlear Implants and the Effect of the Age at Implantation.

OBJECTIVE: We analyzed the long-term changes in speech perception ability of pediatric cochlear implants (CIs) to evaluate the effect of the age at the time of surgery. STUDY DESIGN: Retrospective. SETTING: Tertiary care academic center. PATIENTS: One hundred fourteen prelingually deaf children with CI use duration >10 years. MAIN OUTCOME MEASURES: Categories of auditory performance (CAP) scores and monosyllabic word recognition scores using the Asan-Samsung Korean word list (ASK-WRS) and a conventional word list (KS-WRS) were the main outcomes. Outcomes were compared according to the age at surgery (group I, 1-2 yr; II, 2.1-3 yr; III, 3.1-7 yr; IV, 7.1-13 yr). RESULTS: CAP scores reached plateaus at 2.6 to 3.3 years post-CI; groups I to III showed better scores than group IV. The maximum CAP score was obtained in all children of groups I to III and in 65% of group IV. ASK-WRSs reached plateaus at 3.2 to 4.8 years post-CI. Younger patients at CI operation showed better ASK-WRSs (97, 93, 90, and 54% in groups I-IV, respectively), but the differences were not significant (I versus II and II versus III). Ceiling effect (perfect score) was observed in early groups (67, 44, 30, and 0% in groups I-IV). KS-WRSs, which is a challenging test, reached plateaus at 7.2 to 8.4 years postsurgery with no ceiling effect. Early implantees showed significantly better scores (88, 82, 73, and 46% in groups I-IV). CONCLUSIONS: Speech perception ability after CI showed audiological age-specific improvement evaluated by various test methods. The most challenging test demonstrated long-term performance differences by the age at CI operation.

Activity-expression profiling of glucose-6-phosphate dehydrogenase in tissues of normal and diabetic mice.

Glucose-6-phosphate dehydrogenase (G6PD) plays a principal role in the regulation of oxidative stress by modulating the nicotinamide adenine dinucleotide phosphate pool and is expected to be associated with metabolic diseases such as diabetes mellitus (DM). However, it is unclear whether hyperglycemia increases G6PD activity levels in DM because suitable assays for quantifying the activity in a high-throughput manner are lacking. Using liquid droplet arrays tailored to analyze tissue lysates, we performed G6PD activity profiling in eight tissues of normal and diabetic mice: brain, heart, kidney, liver, lung, muscle, spleen, and thyroid. Diabetic mice exhibited significantly higher G6PD activities in the kidney, liver, spleen, and thyroid than normal mice; no significant difference was found in the brain, heart, lung, or muscle. We also performed G6PD expression profiling in the eight tissues using Western blot analysis. Diabetic mice showed significantly elevated G6PD expression levels in the kidney, lung, spleen, and thyroid compared with normal mice; no significant difference was found in the brain, heart, liver, or muscle. An analysis of G6PD activity-expression profiles demonstrated tissue-specific changes in response to hyperglycemia. Thus, our approach would be helpful for understanding the role of G6PD in tissue-based pathogenesis of diabetic complications.

Accumulation of genetic variants associated with immunity in the selective breeding of broilers.

BACKGROUND: To satisfy an increasing demand for dietary protein, the poultry industry has employed genetic selection to increase the growth rate of broilers by over 400% in the past 50 years. Although modern broilers reach a marketable weight of ~ 2 kg in a short span of 35 days, a speed twice as fast as a broiler 50 years ago, the expedited growth has been associated with several negative detrimental consequences. Aside from heart and musculoskeletal problems, which are direct consequences of additional weight, the immune response is also thought to be altered in modern broilers. RESULTS: Given that identifying the underlying genetic basis responsible for a less sensitive innate immune response would be economically beneficial for poultry breeding, we decided to compare the genomes of two unselected meat control strains that are representative of broilers from 1957 and 1978, and a current commercial broiler line. Through analysis of genetic variants, we developed a custom prioritization strategy to identify genes and pathways that have accumulated genetic changes and are biologically relevant to immune response and growth performance. Our results highlight two genes, TLR3 and PLIN3, with genetic variants that are predicted to enhance growth performance at the expense of immune function. CONCLUSIONS: Placing these new genomes in the context of other chicken lines, reveal genetic changes that have specifically arisen in selective breeding programs that were implemented in the last 50 years.

Unplanned conversion during minimally invasive liver resection for hepatocellular carcinoma: risk factors and surgical outcomes.

PURPOSE: Unplanned conversion is sometimes necessary during minimally invasive liver resection (MILR) of hepatocellular carcinoma (HCC). The aims of this study were to compare surgical outcomes of planned MILR and unplanned conversion and to investigate the risk factors after unplanned conversion. METHODS: We retrospectively analyzed 286 patients who underwent MILR with HCC from January 2006 to December 2017. All patients were divided into a MILR group and an unplanned conversion group. The clinicopathologic characteristics and outcomes were compared between the 2 groups. In addition, surgical outcomes in the conversion group were compared with the planned open surgery group (n = 505). Risk factors for unplanned conversion were analyzed. RESULTS: Of the 286 patients who underwent MILR, 18 patients (6.7%) had unplanned conversion during surgery. The unplanned conversion group showed statistically more blood loss, higher transfusion rate and postoperative complication rate, and longer hospital stay compared to the MILR group, whereas no such difference was observed in comparison with the planned open surgery group. There were no significant differences in overall and disease-free survival among 3 groups. The right-sided sectionectomy (right anterior and posterior sectionectomy), central bisectionectomy and tumor size were risk factors of unplanned conversion. CONCLUSION: Unplanned conversion during MILR for HCC was associated with poor perioperative outcomes, but it did not affect long-term oncologic outcomes in our study. In addition, when planning right-sided sectionectomy or central bisectionectomy for a large tumor (more than 5 cm), we should recommend open surgery or MILR with an informed consent for unplanned open conversions.

Validation of analytical methods for heterocyclic amines in seven food matrices using high-performance liquid chromatography-tandem mass spectrometry.

Heterocyclic amines (HCAs) are potent mutagens generated by the high temperatures of the cooking process. The purpose of this study was to develop and validate analytical methods for HCAs determination using high-performance liquid chromatography-tandem mass spectrometry in seven food matrices: corn oil, milk, 20% ethanol, pork, flat fish, sea mustard (Undaria pinnatifida), and radish. Six isotopically labelled internal standards were used for quantitation, and Chem Elut and Oasis hydrphilic-liphophilic balance cartridges were applied for sample preparation to remove interferences. Calibration curves showed good linearity (R2 > 0.99) in all matrices. The ranges of the method detection limit and method quantitation limit were 0.009-2.35 ng g-1 and 0.025-7.13 ng g-1, respectively. The recoveries ranged from 67.5% to 119.6%. The coefficients of variation ranged from 0.3% to 15.1% for intra-day and ranged from 0.8% to 19.1% for inter-day. The methods were applied to 24 total diet study samples for HCAs quantitation. These results indicate that the established methods are reliable for determining HCAs in various foods.

Changes in Cortical Auditory Evoked Potentials by Ipsilateral, Contralateral and Binaural Speech Stimulation in Normal-Hearing Adults.

OBJECTIVES: Cortical auditory evoked potentials (CAEPs) have been used to examine auditory cortical development or changes in patients with hearing loss. However, there have been no studies analyzing CAEP responses to the different sound stimulation by different stimulation sides. We characterized changes in normal CAEP responses by stimulation sides in normal-hearing adults. METHODS: CAEPs from the right auditory cortex were recorded in 16 adults following unilateral (ipsilateral and contralateral) and bilateral sound stimulation using three speech sounds (/m/, /g/, and /t/). Amplitudes and latencies of the CAEP peaks in three conditions were compared. RESULTS: Contralateral stimulation elicited larger P2-N1 amplitudes (sum of P2 and N1 amplitudes) than ipsilateral stimulation regardless of the stimulation sounds, mostly due to the larger P2 amplitudes obtained, but elicited comparable P2-N1 amplitudes to bilateral stimulation. Although the P2-N1 amplitudes obtained with the three speech sounds were comparable following contralateral stimulation, the /m/ sound elicited the largest P2-N1 amplitude in ipsilateral stimulation condition due to the largest N1 amplitude obtained, whereas /t/ elicited larger a P2-N1 amplitude than /g/ in bilateral stimulation condition due to a larger P2 amplitude. CONCLUSION: Spectrally different speech sounds and input sides are encoded differently at the cortical level in normal-hearing adults. Standardized speech stimuli, as well as specific input sides of speech, are needed to examine normal development or rehabilitation-related changes of the auditory cortex in the future.

The vicious cycle between transglutaminase 2 and reactive oxygen species in hyperglycemic memory-induced endothelial dysfunction.

Clinical trials suggested that the vascular system can remember episodes of poor glycemic control through a phenomenon known as hyperglycemic memory (HGM). HGM is associated with long-term diabetic vascular complications in type 1 and type 2 diabetes, although the molecular mechanism of that association is not clearly understood. We hypothesized that transglutaminase 2 (TGase2) and intracellular reactive oxygen species (ROS) play a key role in HGM-induced vascular dysfunction. We found that hyperglycemia induced persistent oxidative stress, expression of inflammatory adhesion molecules, and apoptosis in the aortic endothelium of HGM mice whose blood glucose levels had been normalized by insulin supplementation. TGase2 activation and ROS generation were in a vicious cycle in the aortic endothelium of HGM mice and also in human aortic endothelial cells after glucose normalization, which played a key role in the sustained expression of inflammatory adhesion molecules and apoptosis. Our findings suggest that the TGase2-ROS vicious cycle plays an important role in HGM-induced endothelial dysfunction.-Lee, J.-Y., Lee, Y.-J., Jeon, H.-Y., Han, E.-T., Park, W. S., Hong, S.-H., Kim, Y.-M., Ha, K.-S. The vicious cycle between transglutaminase 2 and reactive oxygen species in hyperglycemic memory-induced endothelial dysfunction.

Speech Perception Growth Patterns in Prelingual Deaf Children With Bilateral Sequential Cochlear Implantation.

OBJECTIVE: To evaluate speech perception following the first (CI-1) and second (CI-2) cochlear implantation (CI) in children with sequential bilateral CI. STUDY DESIGN: Retrospective. PATIENTS: Seventy children with follow-up for 60 months post CI-1 and 36 months post CI-2. MAIN OUTCOME MEASURES: Word recognition score (WRS) was the main outcome. WRSs were compared by age at CI operation (group A ≤ 3.5 yr, B 3.6-8.6, for CI-1; group I ≤ 3.5 yr, II 3.6-7.0, III 7.1-13, IV > 13, for CI-2). RESULTS: For CI-1, the WRS of group A exceeded 80% at 24 months post procedure, earlier than group B (54 mo). Group A also had a shorter period of CI-1 use up to the WRS plateau than group B. CI-2 showed an initial burst of WRS growth much earlier than CI-1. This initial burst was most robust within 3 months in group II, but modest in group IV. The periods of CI-2 use (11-17 mo) up to the WRS plateau were much shorter than CI-1 (40-64 mo). Group I did not show the best WRS at 1 month post CI but later exceeded the other groups. CONCLUSION: Children received an immediate benefit by a burst of WRS growth from CI-2 earlier than CI-1, even within 3 months, suggesting that CI-1 gets the auditory cortex ready to foster speech processing from CI-2. The CI-2 performance depends on age at CI-2 implantation and on CI-1 performance. Our current findings will be relevant for clinicians who are counselling parents on CI-2 surgery.

Preventive Effects of Thermosensitive Biopolymer-Conjugated C-Peptide against High Glucose-Induced Endothelial Cell Dysfunction.

C-peptide has emerged as a potential drug for treating diabetic complications. However, clinical application of C-peptide is limited by its short half-life during circulation and costly synthesis methods. To overcome these limitations, a biocompatible and thermosensitive biopolymer-C-peptide conjugate composed of human C-peptide genetically conjugated at the C-terminus of nine repeats of lysine-containing elastin-like polypeptide (K9-C-peptide) is generated. K9-C-peptide exhibits reversible thermal phase behavior with a transition temperature dependent on polypeptide concentration. Degradation of K9-C-peptide hydrogel depends on the concentration of four cleavage enzymes as well as the reaction time and frequency of treatments with elastase-2. The preventive effect of K9-C-peptide against high glucose-induced human aortic endothelial cell dysfunction is further investigated. K9-C-peptide inhibits high glucose-induced intracellular reactive oxygen species generation, transglutaminase 2 activation, and apoptosis, similar to the inhibitory effects of human C-peptide. Thus, K9-C-peptide is a potential drug depot for the sustained delivery of C-peptide to treat diabetic complications.

Perturbations of the ZED1 pseudokinase activate plant immunity.

The Pseudomonas syringae acetyltransferase HopZ1a is delivered into host cells by the type III secretion system to promote bacterial growth. However, in the model plant host Arabidopsis thaliana, HopZ1a activity results in an effector-triggered immune response (ETI) that limits bacterial proliferation. HopZ1a-triggered immunity requires the nucleotide-binding, leucine-rich repeat domain (NLR) protein, ZAR1, and the pseudokinase, ZED1. Here we demonstrate that HopZ1a can acetylate members of a family of 'receptor-like cytoplasmic kinases' (RLCK family VII; also known as PBS1-like kinases, or PBLs) and promote their interaction with ZED1 and ZAR1 to form a ZAR1-ZED1-PBL ternary complex. Interactions between ZED1 and PBL kinases are determined by the pseudokinase features of ZED1, and mutants designed to restore ZED1 kinase motifs can (1) bind to PBLs, (2) recruit ZAR1, and (3) trigger ZAR1-dependent immunity in planta, all independently of HopZ1a. A ZED1 mutant that mimics acetylation by HopZ1a also triggers immunity in planta, providing evidence that effector-induced perturbations of ZED1 also activate ZAR1. Overall, our results suggest that interactions between these two RLCK families are promoted by perturbations of structural features that distinguish active from inactive kinase domain conformations. We propose that effector-induced interactions between ZED1/ZRK pseudokinases (RLCK family XII) and PBL kinases (RLCK family VII) provide a sensitive mechanism for detecting perturbations of either kinase family to activate ZAR1-mediated ETI.

Outcome of Cochlear Implantation in Children With Narrow Bony Cochlear Nerve Canal.

OBJECTIVE: To investigate the diameter of the bony cochlear nerve canal (BCNC) as a prognostic indicator of cochlear implantation (CI) in children. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: Two hundred ninety two prelingual deaf children (323 ears) who received CI before the age of 5 years. INTERVENTIONS: CI in pediatric patients. MAIN OUTCOME AND MEASURES: Postoperative auditory performance was analyzed according to the diameter of the BCNC using the Mann-Whitney U test. Using the images of temporal bone computed tomography, patients were grouped according to the diameter of the BCNC: narrow (<1.4 mm, Group 1), normal (Group 2), and other anomalies (Group 3). RESULTS: Group 1 (10.5%) showed a less significant degree of improvement in category of audiological performance (CAP) score than Groups 2 (57.3%) and 3 (32.2%). Scores obtained from both the open-set monosyllabic words and sentence tests were lower in Group 1 than Groups 2 and 3. Of the patients with narrow BCNC, the CAP score of patient with complete stenosis of BCNC (<0.2 mm) was lower than that of patients with BCNC between 0.2 and 0.8 mm, also 0.8 and 1.4 mm. CONCLUSIONS: The improvement in auditory performance was limited in children with narrow BCNC and the narrower the BCNC, the more severe the limitation. However, gradual improvement can be expected and even children with narrow BCNC may be candidates for early CI and rehabilitation.