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Microbial production of medium chain length fatty acids (MCFAs) from renewable resources is becoming increasingly important in establishing a sustainable and clean chemical industry. This review comprehensively summarizes current advances in microbial MCFA production from renewable resources. Detailed information is provided on two major MCFA production pathways using various renewable resources and other auxiliary pathways supporting MCFA production to help understand the fundamentals of bio-based MCFA production. In addition, conventional and well-studied MCFA producers are classified into two categories, natural and synthetic producers, and their characteristics on MCFA production are outlined. Moreover, various engineering strategies employed to achieve the highest MCFAs production up to date are showcased together with key enzymes suggested for MCFA overproduction. Finally, future challenges and perspectives are discussed towards more efficient production of bio-based MCFA production.
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Fatty Acids , Industrial Microbiology , Fatty Acids/biosynthesisABSTRACT
Targeted temperature management is a treatment strategy to lower core body temperature to achieve neuroprotection or reduce elevated intracranial pressure. Therefore, it has been increasingly used in the neurointensive care unit to manage various types of acute neurologic injuries.Current Concepts: Targeted temperature management can be divided into three distinct phases, including induction, maintenance, and rewarming, and each phase has risks and predictable complications. In patients with acute neurocritical illnesses, including traumatic brain injury, subarachnoid hemorrhage, intracranial hemorrhage, and ischemic stroke, brain edema is a potentially life-threatening complication as it raises the intracranial pressure, leading to brain herniation and permanent neurological damage. In this sense, targeted temperature management can be considered the final strategy for medical treatment for controlling an intracranial pressure crisis in patients with severe brain injury.Discussion and Conclusion: In the neurointensive care unit, applying targeted temperature management to patients with severe brain injuries may be challenging. Targeted temperature management in critically ill neurological patients is associated with an increased risk of systemic complications, as hypothermia is prolonged, requiring a comprehensive patient-by-patient assessment of the advantages and disadvantages of treatment. Except for cerebral pressure management, analyses of targeted temperature management in patients with traumatic brain injury and subarachnoid hemorrhage remain controversial regarding its effect on prognosis. Targeted temperature management should be reserved for selective patients, and further studies are needed to improve the efficacy of hypothermia for individual conditions, including intracerebral hemorrhage and ischemic stroke.
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Background@#and Purpose We investigated the impact of comorbidity burden on troponin elevation, with separate consideration of neurological conditions, in patients with acute ischemic stroke (AIS). @*Methods@#This prospective, observational cohort study consecutively enrolled patients with AIS for 2 years. Serum cardiac troponin I was repeatedly measured, and disease-related biomarkers were collected for diagnosis of preassigned comorbidities, including atrial fibrillation (AF), ischemic heart disease (IHD), myocardial hypertrophy (MH), heart failure (HF), renal insufficiency (RI), and active cancer. The severity of neurological deficits and insular cortical ischemic lesions were assessed as neurological conditions. Adjusted associations between these factors and troponin elevation were determined using a multivariate ordinal logistic regression model and area under the receiver operating characteristic curve (AUC). Cox proportional hazards model was used to determine the prognostic significance of comorbidity beyond neurological conditions. @*Results@#Among 1,092 patients (66.5±12.4 years, 63.3% male), 145 (13.3%) and 335 (30.7%) had elevated (≥0.040 ng/mL) and minimally-elevated (0.040–0.010 ng/mL) troponin, respectively. In the adjusted analysis, AF, MH, HF, RI, active cancer, and neurological deficits were associated with troponin elevation. The multivariate model with six comorbidities and two neurological conditions exhibited an AUC of 0.729 (95% confidence interval [CI], 0.698–0.759). In Cox regression, AF, IHD, and HF were associated with adverse cardio-cerebrovascular events, whereas HF and active cancer were associated with mortality. @*Conclusion@#Troponin elevation in patients with AIS can be explained by the burden of comorbidities in combination with neurological status, which explains the prognostic significance of troponin assay.
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Background@#The aims of this study are to review data on 4-months age National Health Screening Program for Infants and Children (NHSPIC) using a National Health Insurance Service (NHIS) database, and to analyze the newborn hearing screening (NHS) results and related characteristics of the 4-months NHSPIC for 7 years in South Korea. @*Methods@#We analyzed a NHIS database of infants who had participated in the 4-month age NHSPIC from 2010 to 2016. According to the results of hearing questionnaires and physical examination, we analyzed the outcomes of NHS and related infantile and socioeconomic factors. @*Results@#Among 3,128,924 of total eligible infants in Korea between the year 2010 and 2016, 69.2% (2,164,621 infants) conducted 4-months age NHSPIC, and 94.4% (2,042,577 infants) of which performed hearing questionnaires regarding NHS. Among the total hearing examinees, premature infants accounted for 3.6%, infants who were hospitalized in the neonatal intensive care unit (NICU) for more than 5 days accounted for 5.6%, and infants with head and neck abnormalities were 0.6%. The NHS performing rate was 79.1% for total hearing examinees in 2010, but gradually increased to 88.9% in 2016. The NHS performing rate in 2016 was 93.4% for premature infants, 91.7% for NICU hospitalized babies. The mean referral rate was 0.6% for total hearing examinees, 1.4% for premature infants, and 2.3% for NICU hospitalized babies. When we analyzed the NHS performing rate and the referral rate according to the household income level, the NHS performing rate of infants in Medical Aid programs was the lowest as 65.6%, and the NHS performing rates in other five levels of NHIS was higher ranging between 85.1% to 86.0%. The referral rate of infants in the Medical Aid program (3.8%) was significantly higher than those of infants in other classes (1.10–1.25%). @*Conclusion@#The estimated overall NHS performing rate in Korea gradually increased and was 88.9% in 2016. The overall referral rate was low as 0.6%, and it was significantly different depending on the infant’s health condition and household income levels. We assume that our finding would help to establish policies managing hearing impaired children, and to develop the customized hearing care service programs considering the household economic levels.
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To maintain normal glucose homeostasis after a meal, it is essential to secrete an adequate amount of insulin from pancreatic β-cells. However, if pancreatic β-cells solely depended on the blood glucose level for insulin secretion, a surge in blood glucose levels would be inevitable after the ingestion of a large amount of carbohydrates. To avoid a deluge of glucose in the bloodstream after a large carbohydrate- rich meal, enteroendocrine cells detect the amount of nutrient absorption from the gut lumen and secrete incretin hormones at scale. Since insulin secretion in response to incretin hormones occurs only in a hyperglycemic milieu, pancreatic β-cells can secrete a “Goldilocks” amount of insulin (i.e., not too much and not too little) to keep the blood glucose level in the normal range. In this regard, pancreatic β-cell sensitivity to glucose and incretin hormones is crucial for maintaining normal glucose homeostasis. In this Namgok lecture 2022, we review the effects of current anti-diabetic medications on pancreatic β-cell sensitivity to glucose and incretin hormones.
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Background and Objectives@#To investigate the diagnostic validity of auditory brainstem response (ABR) in the screening of vestibular schwannoma (VS). @*Subjects and Methods@#Forty patients diagnosed with VS using magnetic resonance imaging who had undergone ABR before treatment between 2005 and 2015 were included. ABR results were considered positive when findings met at least one of the following criteria: 1) absent evoked response, 2) desynchronization of waves other than wave I, 3) interpeak latency (IPL) between waves I and III >2.5 ms, 4) IPL between waves I and V >4.4 ms, 5) wave V interaural latency difference >0.2 ms, and 6) interaural difference in IPL between waves I and V >0.2 ms. @*Results@#The overall sensitivity of ABR was 85.0%. For tumors measuring 10 mm. The sensitivity of tumors confined to the internal acoustic canal was 73.3% compared with 100.0% for tumors confined to the cerebellopontine angle. In patients with serviceable hearing, the mean tumor size was 7.8±2.9 mm in patients with a normal ABR and 15.1±9.4 mm in patients with an abnormal ABR, indicating a significant difference (p10 mm in patients with serviceable hearing, supporting the need for further active diagnostic and treatment modalities in clinical practice.
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Background@#To compare the efficacy and safety of two insulin self-titration algorithms, Implementing New Strategies with Insulin Glargine for Hyperglycemia Treatment (INSIGHT) and EDITION, for insulin glargine 300 units/mL (Gla-300) in Korean individuals with uncontrolled type 2 diabetes mellitus (T2DM). @*Methods@#In a 12-week, randomized, open-label trial, individuals with uncontrolled T2DM requiring basal insulin were randomized to either the INSIGHT (adjusted by 1 unit/day) or EDITION (adjusted by 3 units/week) algorithm to achieve a fasting self-monitoring of blood glucose (SMBG) in the range of 4.4 to 5.6 mmol/L. The primary outcome was the proportion of individuals achieving a fasting SMBG ≤5.6 mmol/L without noct urnal hypoglycemia at week 12. @*Results@#Of 129 individuals (age, 64.1±9.5 years; 66 [51.2%] women), 65 and 64 were randomized to the INSIGHT and EDITION algorithms, respectively. The primary outcome of achievement was comparable between the two groups (24.6% vs. 23.4%, P=0.876). Compared with the EDITION group, the INSIGHT group had a greater reduction in 7-point SMBG but a similar decrease in fasting plasma glucose and glycosylated hemoglobin. The increment of total daily insulin dose was significantly higher in the INSIGHT group than in the EDITION group (between-group difference: 5.8±2.7 units/day, P=0.033). However, body weight was significantly increased only in the EDITION group (0.6±2.4 kg, P=0.038). There was no difference in the occurrence of hypoglycemia between the two groups. Patient satisfaction was significantly increased in the INSIGHT group (P=0.014). @*Conclusion@#The self-titration of Gla-300 using the INSIGHT algorithm was effective and safe compared with that using the EDITION algorithm in Korean individuals with uncontrolled T2DM (ClinicalTrials.gov number: NCT03406663).
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Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.
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Background/Aims@#Recurrent acute myocardial infarction (AMI) is an adverse cardiac event in patients with a first AMI. The predictors of recurrent AMI after the first AMI in patients who underwent successful percutaneous coronary intervention (PCI) have not been elucidated. @*Methods@#We analyzed the data collected from 9,869 patients (63.2 ± 12.4 years, men:women = 7,446:2,423) who were enrolled in the Korea Acute Myocardial Infarction Registry-National Institute of Health between November 2011 and October 2015, had suffered their first AMI and had received successful PCI during the index hospitalization. Multivariable logistic regression analysis was performed to identify the independent predictors of recurrent AMI following the first AMI. @*Results@#The cumulative incidence of recurrent AMI after successful PCI was 3.6% (359/9,869). According to the multivariable logistic regression analysis, the significant predictive factors for recurrent AMI were diabetes mellitus, renal dysfunction, atypical chest pain, and multivessel disease. @*Conclusions@#In this Korean prospective cohort study, the independent predictors of recurrent AMI after successful PCI for the first AMI were diabetes mellitus, renal dysfunction, atypical chest pain, and multivessel disease.
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This case report describes the immediate loading of narrow diameter implants in the mandibular incisor area using full-digital flow. The 3-dimensional position of the implants was planned using digital software, and the corresponding surgical template was fabricated. The implants were inserted immediately after extraction and on the same day, the interim abutment and bridge were placed. At 8 weeks after surgery, the stability of the implants was measured and a digital impression was made using a scan body. Customized titanium abutments and a cementtype full zirconia bridge were delivered. At 36 weeks’ follow-up, no clinical or radiographic complications were detected, and the patient was satisfied with the results.
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Uterine adenomyosis, which is known as a benign gynecological disease, can induce hypercoagulable state and be an uncommon cause of cerebral thromboembolism, as cerebral infarction is common in patients with malignant neoplasm. We report a woman with uterine adenomyosis who shows several episodes of cerebral infarction and discuss the stoke mechanism and treatment of this under-recognized etiology of stroke.
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Background@#Optimal management of primary aldosteronism (PA) is crucial due to the increased risk of cardiovascular and cerebrovascular diseases. Adrenal venous sampling (AVS) is the gold standard method for determining subtype but is technically challenging and invasive. Some PA patients do not benefit clinically from surgery. We sought to develop an algorithm to improve decision- making before engaging in AVS and surgery in clinical practice. @*Methods@#We conducted the ongoing Korean Primary Aldosteronism Study at two tertiary centers. Study A involved PA patients with successful catheterization and a unilateral nodule on computed tomography and aimed to predict unilateral aldosterone-producing adenoma (n=367). Study B involved similar patients who underwent adrenalectomy and aimed to predict postoperative outcome (n=330). In study A, we implemented important feature selection using the least absolute shrinkage and selection operator regression. @*Results@#We developed a unilateral PA prediction model using logistic regression analysis: lowest serum potassium level ≤3.4 mEq/L, aldosterone-to-renin ratio ≥150, plasma aldosterone concentration ≥30 ng/mL, and body mass index <25 kg/m2 (area under the curve, 0.819; 95% confidence interval, 0.774 to 0.865; sensitivity, 97.6%; specificity, 25.5%). In study B, we identified female, hypertension duration <5 years, anti-hypertension medication <2.5 daily defined dose, and the absence of coronary artery disease as predictors of clinical success, using stepwise logistic regression models (sensitivity, 94.2%; specificity, 49.3%). We validated our algorithm in the independent validation dataset (n=53). @*Conclusion@#We propose this new outcome-driven diagnostic algorithm, simultaneously considering unilateral aldosterone excess and clinical surgical benefits in PA patients.
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Background@#Heart rate (HR) monitored by a wearable device (WD) has demonstrated its clinical feasibility for thyrotoxicosis subjects. However, the association of HR monitored by wearables with hypothyroidism has not been examined. We assessed the association between serum thyroid hormone concentration and three WD-HR parameters in hypothyroid subjects. @*Methods@#Forty-four subjects scheduled for radioactive iodine therapy (RAI Tx) after thyroid cancer surgery were included. Thirty subjects were prepared for RAI Tx by thyroid hormone withdrawal (hypothyroidism group) and 14 subjects by recombinant human thyrotropin (control group). Three WD-HR parameters were calculated from the HR data collected during rest, during sleep, and from 2:00 AM to 6:00 AM, respectively. We analyzed the changes in conventionally measured resting HR (On-site rHR) and WDHR parameters relative to thyroid hormone levels. @*Results@#Serum free thyroxine (T4) levels, On-site rHR, and WD-HR parameters were lower in the hypothyroid group than in the control group at the time of RAI Tx. WD-HR parameters also reflected minute changes in free T4 levels. A decrease in On-site rHR and WD-HR parameters by one standard deviation (On-site rHR, approximately 12 bpm; WD-HR parameters, approximately 8 bpm) was associated with a 0.2 ng/dL decrease in free T4 levels (P<0.01) and a 2-fold increase of the odds ratio of hypothyroidism (P<0.01). WD-HR parameters displayed a better goodness-of-fit measure (lower quasi-information criterion value) than On-site rHR in predicting the hypothyroidism. @*Conclusion@#This study identified WD-HR parameters as informative and easy-to-measure biomarkers to predict hypothyroidism.
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Background@#Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids. @*Methods@#The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors. @*Results@#The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT. @*Conclusion@#The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.
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Purpose@#This study analyzed the effects of non-damaging retinal laser therapy (NRT) in patients with chronic central serous chorioretinopathy. @*Methods@#A retrospective study was conducted on patients with chronic central serous chorioretinopathy who were undergoing follow-up with NRT from November 2016 to February 2018. NRT was performed in patients who underwent intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection at least two times with no improvement in visual acuity and a reduced amount of subretinal fluid. Before and after treatment, logMAR best-corrected visual acuity (BCVA) evaluation and subretinal fluid (SRF) according to thickness measurements of the macula determined from optical coherence tomography imagery were performed over a period of at least 6 months. @*Results@#Eighteen eyes of 18 patients (11 male and 7 female) with chronic central serous retinopathy were treated with NRT. The mean age of patients was 54.6 ± 13.19 years old and the mean duration of follow-up was 9.75 ± 3.20 months. The central macular thickness decreased from 375 to 246 nm (p < 0.001) and BCVA improved from 0.48 to 0.40 (p = 0.028). SRF completely resolved in 55.56% of the patients after NRT. @*Conclusions@#In patients with chronic central serous chorioretinopathy, which did not improve even after intravitreal anti-VEGF injection, NRT is a relatively safe and effective treatment.
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Significant progress in pituitary and adrenal diseases was made in 2020. This review presents major translational and clinical advances in research on pituitary and adrenal diseases, encompassing their epidemiology, pathogenesis, diagnosis, and clinical management. We address the controversy regarding the nomenclature of pituitary neuroendocrine tumors, omics-based molecular classification of pituitary adenomas, and novel drugs for Cushing’s disease in the field of pituitary diseases. In the field of adrenal diseases, we cover big data-driven epidemiology of adrenal tumors, steroid profiling as a new diagnostic tool, and the utility of scoring systems in the decision-making process of managing primary aldosteronism. This brief article will broaden readers’ understanding of pituitary and adrenal diseases.
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Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients’ health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.
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Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.
ABSTRACT
Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients’ health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.
ABSTRACT
Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.
