Suppressing the Maintenance of Information in Working Memory Alters Long-term Memory Traces.

The sensory recruitment hypothesis conceptualizes information in working memory as being activated representations of information in long-term memory. Accordingly, changes made to an item in working memory would be expected to influence its subsequent retention. Here, we tested the hypothesis that suppressing information from working memory, which can reduce short-term access to that information, may also alter its long-term neural representation. We obtained fMRI data (n = 25; 13 female / 12 male participants) while participants completed a working memory removal task with scene images as stimuli, followed by a final surprise recognition test of the examined items. We applied a multivariate pattern analysis to the data to quantify the engagement of suppression on each trial, to track the contents of working memory during suppression, and to assess representational changes afterward. Our analysis confirms previous reports that suppression of information in working memory involves focused attention to target and remove unwanted information. Furthermore, our findings provide new evidence that even a single dose of suppression of an item in working memory can (if engaged with sufficient strength) produce lasting changes in its neural representation, particularly weakening the unique, item-specific features, which leads to forgetting. Our study sheds light on the underlying mechanisms that contribute to the suppression of unwanted thoughts and highlights the dynamic interplay between working memory and long-term memory.

Primary Intracranial Ewing Sarcoma With an Unusual Presentation: A Case Report.

Primary extraosseous intracranial Ewing sarcoma (ES) is an extremely rare disease, limited to the pediatric population, that primarily originates in the skull. Here, we present an unusual case of adult Ewing's sarcoma originating from the brain parenchyma. The 50-year-old male patient visited our hospital with severe headache lasting 3 weeks. MRI presented 6.1×6.2×5.2 cm sized heterogeneously enhanced mass containing peritumoral edema in the right frontal lobe. The patient underwent right frontal craniotomy, at which time the gray and red masses adhered to the surrounding brain parenchyma. The mass was completely resected using neuronavigation and electrophysiological monitoring. Histopathological examination revealed ES-compatible findings of small round cell tumor and CD-99 positive membranous immunostaining. Next generation sequencing revealed translocation and fusion of EWSR1 and FLI1, consistent with a confirmed diagnosis of ES. Consequently, the patient underwent postoperative radiotherapy. The present case revealed adult primary intracranial ES arising from the frontal lobe. Although its etiology remains poorly understood, intraparenchymal ES should be included in the differential diagnosis of parenchymal brain tumors.

Typology and implications of verified attacks on health care in Ukraine in the first 18 months of war.

Attacks on health care are part of the spectrum of threats that health care endures during conflict. Protecting health care services against attacks depends on understanding the nature and types of attacks that occur during conflict. The World Health Organisation has implemented the Surveillance System for Attacks on Health Care (SSA) in Ukraine since 2020, and the system has continued to monitor and report on attacks on health care during the war in Ukraine. This study aims to analyse the data reported through the SSA for the first 18 months of the war. This paper involves a retrospective, descriptive study based on the analysis of publicly available SSA data of all incidents of attacks on health care in Ukraine reported through the SSA between February 24th 2022 and August 24th 2023. Out of the 1503 verified attacks, 37% occurred in the initial six weeks of the war. Attacks involving violence with heavy weapons were among the most common incidents reported (83%). The reported attacks were associated with a total of 113 deaths and 211 injuries among health care workers and patients: 32 (2%) attacks were associated with a death of a health care worker or patient, and 63 (4%) were associated with an injury. Health transports facing attacks had a higher probability of experiencing casualties than other health resources (p<0.0001, RR 3.1, 95%CI 1.9-4.9). In conclusion, the burden of attacks on health care in Ukraine was high and sustained over the course of the first 18 months of the war. Reported casualties were not homogenously distributed among attack incidents, but occurred in a set of high-casualty incidents. Health transports were found to be particularly vulnerable. In addition to continued calls for a cessation of hostilities, prevention, protection, mitigation, and reconstruction strategies are urgently required.

Reference Standards for C-Peptide in Korean Population: A Korean Endocrine Hormone Reference Standard Data Center Study.

BACKGRUOUND: The Korean Endocrine Hormone Reference Standard Data Center (KEHRS DC) has created reference standards (RSs) for endocrine hormones since 2020. This study is the first of its kind, wherein the KEHRS DC established RSs for serum Cpeptide levels in a healthy Korean population. METHODS: Healthy Korean adults were recruited from May 2021 to September 2023. After excluding participants according to our criteria, serum samples were collected; each participant could then choose between fasting glucose only or fasting glucose plus an oral glucose tolerance test (OGTT). If their sample showed high glucose (≥100 mg/dL) or hemoglobin A1c (HbA1c) (≥5.70%), their C-peptide levels were excluded from analyzing the RSs. RESULTS: A total of 1,532 participants were recruited; however, only the data of 1,050 participants were analyzed after excluding those whose samples showed hyperglycemia or high HbA1c. Post-30-minute OGTT data from 342 subjects and post-120-minute OGTT data from 351 subjects were used. The means±2 standard deviations and expanded uncertainties of fasting, post-30-minute and 120-minute OGTT C-peptide levels were 1.26±0.82 and 0.34-3.18, 4.74±3.57 and 1.14-8.33, and 4.85±3.58 and 1.25-8.34 ng/mL, respectively. Serum C-peptide levels correlated with obesity, serum glucose levels, and HbA1c levels. CONCLUSION: The RSs for serum C-peptide levels established in this study are expected to be useful in both clinical and related fields.

Alterations in Plasma Lipid Profile before and after Surgical Removal of Soft Tissue Sarcoma.

Soft tissue sarcoma (STS) is a relatively rare malignancy, accounting for about 1% of all adult cancers. It is known to have more than 70 subtypes. Its rarity, coupled with its various subtypes, makes early diagnosis challenging. The current standard treatment for STS is surgical removal. To identify the prognosis and pathophysiology of STS, we conducted untargeted metabolic profiling on pre-operative and post-operative plasma samples from 24 STS patients who underwent surgical tumor removal. Profiling was conducted using ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry. Thirty-nine putative metabolites, including phospholipids and acyl-carnitines were identified, indicating changes in lipid metabolism. Phospholipids exhibited an increase in the post-operative samples, while acyl-carnitines showed a decrease. Notably, the levels of pre-operative lysophosphatidylcholine (LPC) O-18:0 and LPC O-16:2 were significantly lower in patients who experienced recurrence after surgery compared to those who did not. Metabolic profiling may identify aggressive tumors that are susceptible to lipid synthase inhibitors. We believe that these findings could contribute to the elucidation of the pathophysiology of STS and the development of further metabolic studies in this rare malignancy.

Stimulus shapes strategy: Effects of stimulus characteristics and individual differences in academic achievement on the neural mechanisms engaged during the N-back task.

This fMRI study of 126 youth explored whether the neural mechanisms underlying the N-back task, commonly used to examine executive control over the contents of working memory, are associated with individual differences in academic achievement in reading and math. Moreover, the study explored whether these relationships occur regardless of the nature of the stimulus being manipulated in working memory (letters, numbers, nonsense shapes) or whether these relationships are specific to achievement domain and stimulus type (i.e., letters for reading and numbers for math). The results indicated that higher academic achievement in each of reading and math was associated with greater activation of dorsolateral prefrontal cortex in the N-back task regardless of stimulus type (i.e., did not differ for letters and numbers), suggesting that at least some aspects of the neural mechanisms underlying these academic domains are executive in nature. In addition, regardless of level of academic achievement, prefrontal regions were engaged to a greater degree for letters than numbers than nonsense shapes. In contrast, nonsense shapes yielded greater hippocampal activation than letters and numbers. Potential reasons for this pattern of findings are discussed.

OsLRR-RLP2 Gene Regulates Immunity to Magnaporthe oryzae in Japonica Rice.

Rice is an important cereal crop worldwide, the growth of which is affected by rice blast disease, caused by the fungal pathogen Magnaporthe oryzae. As climate change increases the diversity of pathogens, the disease resistance genes (R genes) in plants must be identified. The major blast-resistance genes have been identified in indica rice varieties; therefore, japonica rice varieties with R genes now need to be identified. Because leucine-rich repeat (LRR) domain proteins possess R-gene properties, we used bioinformatics analysis to identify the rice candidate LRR domain receptor-like proteins (OsLRR-RLPs). OsLRR-RLP2, which contains six LRR domains, showed differences in the DNA sequence, containing 43 single-nucleotide polymorphisms (SNPs) in indica and japonica subpopulations. The results of the M. oryzae inoculation analysis indicated that indica varieties with partial deletion of OsLRR-RLP2 showed susceptibility, whereas japonica varieties with intact OsLRR-RLP2 showed resistance. The oslrr-rlp2 mutant, generated using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), showed increased pathogen susceptibility, whereas plants overexpressing this gene showed pathogen resistance. These results indicate that OsLRR-RLP2 confers resistance to rice, and OsLRR-RLP2 may be useful for breeding resistant cultivars.

Neural Systems Underlying the Implementation of Working Memory Removal Operations.

Recently, multi-voxel pattern analysis has verified that information can be removed from working memory (WM) via three distinct operations replacement, suppression, or clearing compared to information being maintained ( Kim et al., 2020). While univariate analyses and classifier importance maps in Kim et al. (2020) identified brain regions that contribute to these operations, they did not elucidate whether these regions represent the operations similarly or uniquely. Using Leiden-community-detection on a sample of 55 humans (17 male), we identified four brain networks, each of which has a unique configuration of multi-voxel activity patterns by which it represents these WM operations. The visual network (VN) shows similar multi-voxel patterns for maintain and replace, which are highly dissimilar from suppress and clear, suggesting this network differentiates whether an item is held in WM or not. The somatomotor network (SMN) shows a distinct multi-voxel pattern for clear relative to the other operations, indicating the uniqueness of this operation. The default mode network (DMN) has distinct patterns for suppress and clear, but these two operations are more similar to each other than to maintain and replace, a pattern intermediate to that of the VN and SMN. The frontoparietal control network (FPCN) displays distinct multi-voxel patterns for each of the four operations, suggesting that this network likely plays an important role in implementing these WM operations. These results indicate that the operations involved in removing information from WM can be performed in parallel by distinct brain networks, each of which has a particular configuration by which they represent these operations.

Efficacy and safety of denosumab treatment for Korean patients with Stage 3b-4 chronic kidney disease and osteoporosis.

BACKGROUND/AIMS: We evaluated the efficacy and safety of denosumab treatment in severe chronic kidney disease (CKD) patients with osteoporosis. We also investigated whether the treatment affects the coronary artery calcifications. METHODS: Twenty-seven postmenopausal women with Stage 3b-4 CKD and osteoporosis were enrolled. Twenty patients received denosumab plus calcium carbonate and vitamin D, and seven controls received calcium carbonate and vitamin D for 1 year. Dual-energy X-ray absorptiometry and coronary artery calcium (CAC) scoring computed tomography were performed before and after treatment. Hypocalcemic symptoms and serum calcium levels were evaluated. RESULTS: After 1 year of treatment, the percent changes of femur neck (3.6 ± 3.2% vs. -0.7 ± 4.4%, p = 0.033) and total hip (3.4 ± 3.8% vs. -1.9 ± 2.1%, p = 0.001) bone mineral density (BMD) were significantly increased in the denosumab treated group compared to the control group. However, the percent change of lumbar spine BMD did not differ between two groups (5.6 ± 5.9% vs. 2.7 ± 3.9%, p = 0.273). The percent change of bone alkaline phosphatase was significantly different in the denosumab-treated group and control group (-31.1 ± 30.0% vs. 0.5 ± 32.0%, p = 0.027). CAC scores did not differ between groups. No hypocalcemic events occurred in both groups. CONCLUSION: If carefully monitored and supplemented with calcium and vitamin D, denosumab treatment for 1 year provides significant benefits in patients with Stage 3b-4 CKD and osteoporosis. However, denosumab treatment did not affect coronary artery calcifications in these patients.

"It is because of the love for the job that we are still here": Mental health and psychosocial support among health care workers affected by attacks in the Northwest and Southwest regions of Cameroon.

Attacks on health care have important consequences for the mental health (MH) and work availability of health care workers (HCW). In the conflict-affected Northwest and Southwest (NWSW) regions of Cameroon, health care attacks are common; however, little is known on the MH burden and/or (mental) health-seeking behavior among affected HCW. We therefore conducted a survey on mental conditions (relying on SRQ-20 and WASSS assessments) and access to MH services among 470 HCW from 12 districts in NWSW Cameroon in January-February 2022. In-depth interviews on personal experiences with attacks and on accessing MH services were conducted with a subset of 96 HCW. Among surveyed HCW, 153 (33%) had experienced an attack in the past 6 months, and a further 121 (26%) had experienced attacks more than 6 months ago. HCW facing attacks <6 months ago had significantly higher odds of exhibiting mental disorders (aOR 5.8, 95%CI 3.0-11.3, p<0.001) and of being unable to function (aOR 3.3, 95%CI 1.9-5.7, p<0.001). HCW who experienced an attack >6 months also had higher odds of being unable to function (aOR 2.9, 95%CI 1.7-5.2, p<0.001), and of missing time off work in the week preceding the survey (aOR 3.1, 95%CI 1.8-5.5, p<0.001). Previous access to MH services was also higher among HCW facing attacks. HCW showed a good understanding of the added values of accessing MH services, but faced multiple access barriers (including poor availability of services and their own prioritization of the care of others) and indicated a preference for self-care, peer-support and/or religious support. In conclusion, health care attacks in NWSW Cameroon contributed significantly to severe mental conditions and absenteeism rates among HCW. Strengthening access to MH support among attack-affected HCW is indicated; this should include strengthening of formal MH services and building the capacity of HCW and religious leaders to provide peer-support.

Ocean fronts as decadal thermostats modulating continental warming hiatus.

Over the past decade, an unexpected cooling trend has been observed in East Asia and North America during winter. Climate model simulations suggest that this pattern of stalled warming, besides accelerated warming, will repeat throughout the course of global warming, influenced by the natural decade-long variations in the climate system. However, understanding the exact factors affecting the pace of warming remains a challenge. Here we show that a pause in warming over continental areas-namely, local warming hiatus-can be accompanied by excessive heat accumulation north of the ocean fronts. This oceanic condition, often manifesting in the form of marine heatwaves, constrains the subseasonal growth of atmospheric planetary waves, significantly increasing the likelihood of cold extremes in downstream continents. Our results underscore the importance of closely monitoring changing ocean fronts in response to human-induced warming, which can potentially reshape the inherent decade-long fluctuations within regional climates over the long term.

Neonatal outcomes of early preterm births according to the delivery indications.

OBJECTIVE: To compare the neonatal outcomes of early preterm births according to delivery indications and determine the obstetric risk factors associated with adverse outcomes. METHODS: We retrospectively studied pregnancies delivered between 22 + 0 and 26 + 6 weeks at the tertiary center between April 2013 and April 2022. Stillbirths, elective termination of pregnancy, and multifetal pregnancies were excluded. Patients were classified into two groups according to delivery indications: spontaneous preterm birth (sPTB) due to premature rupture of membranes (PROM), preterm labor, or acute cervical insufficiency; and indicated preterm birth (iPTB). Obstetric and neonatal outcomes were compared between the groups. RESULTS: Of the 121 neonates, 73 % (88/121) underwent sPTB. The overall survival rates were 73 % and 49 % in the sPTB and iPTB groups, respectively (p = 0.017). Multivariate logistic regression analysis was performed with adjustment for gestational age at delivery, fetal growth restriction, cesarean section, histological chorioamnionitis, and funisitis. Moreover, in the 1-year follow-up, the proportion of body mass below the third percentile was significantly higher in the iPTB-group than in the sPTB-group (53 % vs. 20 %, p = 0.019). Furthermore, diagnoses of developmental delay and cerebral palsy were slightly higher in the iPTB-group (33 % and 20 %, respectively) than in the sPTB-group (27 % and 9 %, respectively); however, this difference was not statistically significant. CONCLUSIONS: In early preterm births, iPTB was associated with a higher neonatal mortality than sPTB.

Analysis of Watson for oncology and clinicians' treatment recommendations for patients with breast cancer in Korea: A single center experience.

Background: Various clinical applications have been attempted using artificial intelligence (AI) clinical decision support system (CDSS), and it has become a starting point for personalized cancer treatment. We aimed to identify the degree of agreement between the AI-CDSS, Watson for Oncology (WFO), and the clinician in treatment recommendations for Korean breast cancer patients and to provide guidelines for future improvement. Methods: One hundred and eighty-three breast cancer patients who underwent treatment at the Pusan National University Hospital between January 1, 2016 and May 31, 2017 were enrolled in this study. The concordance between WFO's and clinicians' treatment recommendations were examined according to various factors. Results: WFO gave the same treatment option recommendations as clinicians in 74 (40.4%) of the cases. According to the logistic regression, the difference in recommendation concordance between stage I and stage III was statistically significant (P = 0.004), and there was no difference among other factors. Conclusion: The concordance of treatment recommendations was low overall. However, this is largely attributable to the differences of medical insurance system and healthcare environment between the United States and Korea. In the future, region-specific features should be considered or reflected during the development of AI-CDSS.

Treatment outcomes of advanced/metastatic extramammary Paget's disease in Korean patients: KCSG-RC20-06.

BACKGROUND: Extramammary Paget's disease (EMPD) is rare. There are no standard treatments due to its rarity and few clinical trials. METHODS: The objective of this multicenter study was to investigate treatment outcomes of Korean patients with advanced/metastatic EMPD. Data were collected retrospectively from 14 institutions participating in Korean Cancer Study Group (KCSG) Rare Cancer Committee. RESULTS: A total of 37 patients were identified. Of these 37 patients, 6 received locoregional therapy as a first-line treatment. In 31 patients who received systemic chemotherapy as a first-line treatment, platinum-based chemotherapy (n = 22) achieved an objective response rate (ORR) of 45.5% and a median progression-free survival (PFS) of 7.89 months. Taxane-based chemotherapy (n = 8) achieved an objective response rate of 62.5% and median PFS of 9.73 months. In second-line chemotherapy, platinum-based chemotherapy (n = 4) had a disease control rate (DCR) of 75.0% and median PFS of 3.45 months. Taxane-based chemotherapy (n = 8) had a DCR of 75.0% and a median PFS of 8.67 months. Six patients received anti-human epidermal growth factor receptor 2 (HER2) antibody during first- and second-line chemotherapy. Overall, systemic chemotherapy combined with anti-HER2 antibody had an ORR of 100% and a median PFS of 13.31 months. The ORR and PFS with systemic chemotherapy combined with trastuzumab was better than platinum- and taxane-based chemotherapy only. CONCLUSIONS: Due to its rarity, advanced or metastatic EMPD still has no established standard treatment. Results of our study indicate that the combination of trastuzumab with taxane has longer survival than trastuzumab monotherapy or conventional platinum- or taxane-based chemotherapy.

Oculomotor fatigability with decrements of saccade and smooth pursuit for diagnosis of myasthenia gravis.

BACKGROUND AND OBJECTIVES: As the efficacy of current diagnostic methods for myasthenia gravis (MG) remains suboptimal, there is ongoing interest in developing more effective diagnostic models. As oculomotor fatigability is one of the most common and diagnostic symptoms in MG, we aimed to investigate whether quantitative saccadic and smooth-pursuit fatigability analyses with video-oculography (VOG) are useful for diagnosis of MG. METHODS: A convenience cohort of 46 MG patients was recruited prospectively, including 35 with ocular and 11 with generalized MG (mean age, 50.9 ± 14.5 years; 17 females); 24 healthy controls (HCs) (mean age, 50.6 ± 16.3 years; 13 females) also were enrolled. Seventy-five repetitive saccades and smooth pursuits were recorded in ranges of 20° (horizontal plane) and 15° (vertical plane) using a three-dimensional VOG system. Based on the oculomotor range of the second saccade and smooth pursuit and the mean ranges of the last five of each, the estimated decrements (%) reflecting oculomotor fatigability were calculated. RESULTS: The baseline oculomotor ranges did not show significant difference between the MG and HCs groups. However, following repetitive saccades and pursuits, the oculomotor ranges were decreased substantially during the last five cycles compared to baseline in the MG group. No such decrements were observed in the HC group (p < 0.01, Mann-Whitney U test). Receiver operating characteristic (ROC) analysis revealed that repetitive vertical saccades yielded the best differentiation between the MG and HC groups, with a sensitivity of 78.3% and specificity of 95.8% when using a decrement with an amplitude of 6.4% as the cutoff. CONCLUSION: This study presents an objective and reproducible method for measuring decrements of oculomotor ranges after repetitive saccadic and pursuit movements. Quantification of oculomotor fatigability using VOG could be a sensitive and specific diagnostic tool for MG and allows easy, cost-effective, accurate, and non-invasive measurements. CLASSIFICATION OF EVIDENCE: This study provides class III evidence that VOG-based quantification of saccadic and pursuit fatigability accurately identifies patients with MG.

Enhanced Ca2+-channeling complex formation at the ER-mitochondria interface underlies the pathogenesis of alcohol-associated liver disease.

Ca2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation in ALD remain elusive. Here, we demonstrate that an aberrant increase in hepatic GRP75-mediated mitochondria-associated ER membrane (MAM) Ca2+-channeling (MCC) complex formation promotes mitochondrial dysfunction in vitro and in male mouse model of ALD. Unbiased transcriptomic analysis reveals PDK4 as a prominently inducible MAM kinase in ALD. Analysis of human ALD cohorts further corroborate these findings. Additional mass spectrometry analysis unveils GRP75 as a downstream phosphorylation target of PDK4. Conversely, non-phosphorylatable GRP75 mutation or genetic ablation of PDK4 prevents alcohol-induced MCC complex formation and subsequent mitochondrial Ca2+ accumulation and dysfunction. Finally, ectopic induction of MAM formation reverses the protective effect of PDK4 deficiency in alcohol-induced liver injury. Together, our study defines a mediatory role of PDK4 in promoting mitochondrial dysfunction in ALD.

Morbidity and Mortality Trends in Preterm Infants of <32 Weeks Gestational Age with Severe Intraventricular Hemorrhage : A 14-Year Single-Center Retrospective Study.

OBJECTIVE: Owing to advances in critical care treatment, the overall survival rate of preterm infants born at a gestational age (GA) <32 weeks has consistently improved. However, the incidence of severe intraventricular hemorrhage (IVH) has persisted, and there are few reports on in-hospital morbidity and mortality. Therefore, the aim of the present study was to investigate trends surrounding in-hospital morbidity and mortality of preterm infants with severe IVH over a 14-year period. METHODS: This single-center retrospective study included 620 infants born at a GA <32 weeks, admitted between January 2007 and December 2020. After applying exclusion criteria, 596 patients were included in this study. Infants were grouped based on the most severe IVH grade documented on brain ultrasonography during their admission, with grades 3 and 4 defined as severe. We compared in-hospital mortality and clinical outcomes of preterm infants with severe IVH for two time periods : 2007-2013 (phase I) and 2014-2020 (phase II). Baseline characteristics of infants who died and survived during hospitalization were analyzed. RESULTS: A total of 54 infants (9.0%) were diagnosed with severe IVH over a 14-year period; overall in-hospital mortality rate was 29.6%. Late in-hospital mortality rate (>7 days after birth) for infants with severe IVH significantly improved over time, decreasing from 39.1% in phase I to 14.3% in phase II (p=0.043). A history of hypotension treated with vasoactive medication within 1 week after birth (adjusted odds ratio, 7.39; p=0.025) was found to be an independent risk factor for mortality. When comparing major morbidities of surviving infants, those in phase II were significantly more likely to have undergone surgery for necrotizing enterocolitis (NEC) (29.2% vs. 0.0%; p=0.027). Additionally, rates of late-onset sepsis (45.8% vs. 14.3%; p=0.049) and central nervous system infection (25.0% vs. 0.0%; p=0.049) were significantly higher in phase II survivors than in phase I survivors. CONCLUSION: In-hospital mortality in preterm infants with severe IVH decreased over the last decade, whereas major neonatal morbidities increased, particularly surgical NEC and sepsis. This study suggests the importance of multidisciplinary specialized medical and surgical neonatal intensive care in preterm infants with severe IVH.

Effects of once-weekly dulaglutide on juvenile type 2 diabetes mellitus and obesity in Korea: a pilot study.

PURPOSE: We sought to investigate the effects and side effects of once-weekly dulaglutide treatment for type 2 diabetes mellitus (T2DM) in patients <18 years of age in Korea. METHODS: : From the Eulji University Hospital database, we identified all patients <18 years of age diagnosed with T2DM and treated with dulaglutide from January 1, 2017, to July 31, 2022. RESULTS: We identified 5 patients <18 years of age treated with dulaglutide for T2DM management. Their mean (standard deviation [SD]) age was 16.6 (0.5) years. Four (80%) patients were female. The mean (SD) body mass index was 29.4 (5.1) kg/m2, and the mean (SD) age at diagnosis was 15.2 (1.6) years. Four patients had been treated previously with metformin alone or in combination with insulin. Four patients were treated with 1.5 mg of dulaglutide and one was treated with 0.75 mg of dulaglutide. The mean (SD) hemoglobin A1c concentrations at baseline, 3 months after treatment, and 1 year after treatment, respectively, were 10.0% (2.2%), 6.5% (1.5%), and 6.7% (1.4%), with significant differences. In addition, at baseline, 3 months after treatment, and 1 year after treatment, the mean (SD) body weight values were 79.7 (13.3) kg, 80.2 (14.0) kg, and 81.1 (15.3) kg, with no significant difference. CONCLUSION: Use of once-weekly dulaglutide for juvenile T2DM ensures very good glycemic control, with few side effects and good adherence, indicating its potential as a promising therapeutic agent in this age group. Nationwide studies are warranted to confirm our results.

Mitochondrial fragmentation and donut formation enhance mitochondrial secretion to promote osteogenesis.

Mitochondrial components have been abundantly detected in bone matrix, implying that they are somehow transported extracellularly to regulate osteogenesis. Here, we demonstrate that mitochondria and mitochondrial-derived vesicles (MDVs) are secreted from mature osteoblasts to promote differentiation of osteoprogenitors. We show that osteogenic induction stimulates mitochondrial fragmentation, donut formation, and secretion of mitochondria through CD38/cADPR signaling. Enhancing mitochondrial fission and donut formation through Opa1 knockdown or Fis1 overexpression increases mitochondrial secretion and accelerates osteogenesis. We also show that mitochondrial fusion promoter M1, which induces Opa1 expression, impedes osteogenesis, whereas osteoblast-specific Opa1 deletion increases bone mass. We further demonstrate that secreted mitochondria and MDVs enhance bone regeneration in vivo. Our findings suggest that mitochondrial morphology in mature osteoblasts is adapted for extracellular secretion, and secreted mitochondria and MDVs are critical promoters of osteogenesis.

Long-term management of Graves disease: a narrative review.

Graves disease (GD) is the most common cause of hyperthyroidism, accounting for more than 90% of cases in Korea. Patients with GD are treated with any of the following: antithyroid drugs (ATDs), radioactive iodine (RAI) therapy, or thyroidectomy. Most patients begin treatment with ATDs, and clinical guidelines suggest that the appropriate treatment period is 12 to 18 months. While RAI treatment and surgery manage thyrotoxicosis by destroying or removing thyroid tissue, ATDs control thyrotoxicosis by inhibiting thyroid hormone synthesis and preserving the thyroid gland. Although ATDs efficiently control thyrotoxicosis symptoms, they do not correct the main etiology of GD; therefore, frequent relapses can follow. Recently, a large amount of data has been collected on long-term ATDs for GD, and low-dose methimazole (MMZ) is expected to be a good option for remission. For the long-term management of recurrent GD, it is important to induce remission by evaluating the patient's drug response, stopping ATDs at an appropriate time, and actively switching to surgery or RAI therapy, if indicated. Continuing drug treatment for an extended time is now encouraged in patients with a high possibility of remission with low-dose MMZ. It is also important to pay attention to the quality of life of the patients. This review aimed to summarize the appropriate treatment methods and timing of treatment transition in patients who relapsed several times while receiving treatment for GD.