Rational design, synthesis, biological evaluation, and molecular modeling of novel naphthamide derivatives possessing potent, reversible, and competitive inhibitory mode of action over human monoamine oxidase.

Herein, a novel series of naphthamide derivatives has been rationally developed, synthesized, and evaluated for their inhibitory activity against monoamine oxidase (MAO) and cholinesterase (ChE) enzymes. Compared to the reported naphthalene-based hit IV, the new naphthamide hybrids 2a, 2c, 2g and 2h exhibited promising MAO inhibitory activities; with an IC50 value of 0.294 µM, compound 2c most potently inhibited MAO-A, while compound 2g exhibited most potent MAO-B inhibitory activity with an IC50 value of 0.519 µM. Compounds 2c and 2g showed selectivity index (SI) values of 6.02 for MAO-A and 2.94 for MAO-B, respectively. On the other hand, most compounds showed weak inhibitory activity against ChEs except 2a and 2h over butyrylcholinesterase (BChE). The most potent compounds 2c and 2g were found to be competitive and reversible MAO inhibitors based on kinetic and reversibility studies. Plausible interpretations of the observed biological effects were provided through molecular docking simulations. The drug-likeness predicted by SwissADME and Osiris property explorer showed that the most potent compounds (2a, 2c, 2g, and 2h) obey Lipinski's rule of five. Accordingly, in the context of neurological disorders, hybrids 2c and 2g may contribute to the identification of safe and potent therapeutic approaches in the near future.

Prediction of hospitalization and waiting time within 24 hours of emergency department patients with unstructured text data.

Overcrowding of emergency departments is a global concern, leading to numerous negative consequences. This study aimed to develop a useful and inexpensive tool derived from electronic medical records that supports clinical decision-making and can be easily utilized by emergency department physicians. We presented machine learning models that predicted the likelihood of hospitalizations within 24 hours and estimated waiting times. Moreover, we revealed the enhanced performance of these machine learning models compared to existing models by incorporating unstructured text data. Among several evaluated models, the extreme gradient boosting model that incorporated text data yielded the best performance. This model achieved an area under the receiver operating characteristic curve score of 0.922 and an area under the precision-recall curve score of 0.687. The mean absolute error revealed a difference of approximately 3 hours. Using this model, we classified the probability of patients not being admitted within 24 hours as Low, Medium, or High and identified important variables influencing this classification through explainable artificial intelligence. The model results are readily displayed on an electronic dashboard to support the decision-making of emergency department physicians and alleviate overcrowding, thereby resulting in socioeconomic benefits for medical facilities.

A novel indole derivative, 2-{3-[1-(benzylsulfonyl)piperidin-4-yl]-2-methyl-1H-indol-1-yl}-1-(pyrrolidin-1-yl)ethenone, suppresses hedgehog signaling and drug-resistant tumor growth.

The Hedgehog (Hh) signaling pathway plays important roles in various physiological functions. Several malignancies, such as basal cell carcinoma (BCC) and medulloblastoma (MB), have been linked to the aberrant activation of Hh signaling. Although therapeutic drugs have been developed to inhibit Hh pathway-dependent cancer growth, drug resistance remains a major obstacle in cancer treatment. Here, we show that the newly identified, 2-{3-[1-(benzylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]-2-methyl-1H-indol-1-yl}-1-(pyrrolidin-1-yl)ethenone analog (LKD1214) exhibits comparable potency to vismodegib in suppressing the Hh pathway activation. LKD1214 represses Smoothened (SMO) activity by blocking its ciliary translocation. Interestingly, we also identified that it has a distinctive binding interface with SMO compared with other SMO-regulating chemicals. Notably, it maintains an inhibitory activity against the SmoD477H mutant, as observed in a patient with vismodegib-resistant BCC. Furthermore, LKD1214 inhibits tumor growth in the mouse model of MB. Collectively, these findings suggest that LKD1214 has the therapeutic potential to overcome drug-resistance in Hh-dependent cancers.

Enhancement of Solubility, Stability, Cellular Uptake, and Bioactivity of Curcumin by Polyvinyl Alcohol.

The biological activities and related mechanisms of curcumin, a major polyphenolic compound in turmeric, the rhizome of Curcuma longa, have been extensively investigated. Due to its poor solubility in water, the analysis of curcumin's biological activities is limited in most aqueous experimental systems. In the present study, the effects of polyvinyl alcohol (PVA), a dietary-compatible vehicle, on the solubility, stability, cellular uptake, and bioactivities of curcumin were investigated. Curcumin solubility was improved significantly by PVA; the color intensity of curcumin aqueous solution in the presence of PVA increased concentration-dependently with its peak shift to a shorter wavelength. Improved suspension stability and photostability of curcumin in an aqueous solution were also observed in the presence of PVA, even at 62.5 µg/mL. The scavenging activities of curcumin against DPPH, ABTS, AAPH radicals, and nitric oxide were enhanced significantly in the presence of PVA. PVA at 250 µg/mL also significantly enhanced the cytotoxic activity of curcumin against both HCT 116 colon cancer and INT 407 (HeLa-derived) embryonic intestinal cells by reducing the IC50 from 16 to 11 µM and 25 to 15 µM, respectively. PVA improved the cellular uptake of curcumin in a concentration-dependent manner in INT 407 cells; it increased the cellular levels more effectively at lower curcumin treatment concentrations. The present results indicate that PVA improves the solubility and stability of curcumin, and changes in these chemical behaviors of curcumin in aqueous systems by PVA could enhance the bioavailability and pharmacological efficacy of curcumin.

Development of a web-based care networking system to support visiting healthcare professionals in the community.

BACKGROUND: The role of visiting health services has been proven to be effective in promoting the health of older populations. Hence, developing a web system for nurses may help improve the quality of visiting health services for community-dwelling frail older adults. This study was conducted to develop a web application that reflects the needs of visiting nurses. METHODS: Visiting nurses of public health centers and community centers in South Korea participated in the design and evaluation process. Six nurses took part in the focus group interviews, and 21 visiting nurses and community center managers participated in the satisfaction evaluation. Focus group interviews were conducted to identify the needs of visiting nurses with respect to system function. Based on the findings, a web application that can support the effective delivery of home visiting services in the community was developed. An artificial intelligence (AI) algorithm was also developed to recommend health and welfare services according to each patient's health status. After development, a structured survey was conducted to evaluate user satisfaction with system features using Kano's model. RESULTS: The new system can be used with mobile devices to increase the mobility of visiting nurses. The system includes 13 features that support the management of patient data and enhance the efficiency of visiting services (e.g., map, navigation, scheduler, protocol archives, professional advice, and online case conferencing). The user satisfaction survey revealed that nurses showed high satisfaction with the system. Among all features, the nurses were most satisfied with the care plan, which included AI-based recommendations for community referral. CONCLUSIONS: The system developed from the study has attractive features for visiting nurses and supports their essential tasks. The system can help with effective case management for older adults requiring in-home care and reduce nurses' workload. It can also improve communication and networking between healthcare and long-term care institutions.

Long-Term Efficacy and Safety of Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria and High Disease Burden: Real-World Data From Korea.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. METHODS: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009-2020 were enrolled. RESULTS: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. CONCLUSION: These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

Targeting the interaction of AIMP2-DX2 with HSP70 suppresses cancer development.

A tumorigenic factor, AIMP2 lacking exon 2 (AIMP2-DX2), is often upregulated in many cancers. However, how its cellular level is determined is not understood. Here, we report heat-shock protein HSP70 as a critical determinant for the level of AIMP2-DX2. Interaction of the two factors was identified by interactome analysis and structurally determined by X-ray crystallography and NMR analyses. HSP70 recognizes the amino (N)-terminal flexible region, as well as the glutathione S-transferase domain of AIMP2-DX2, via its substrate-binding domain, thus blocking the Siah1-dependent ubiquitination of AIMP2-DX2. AIMP2-DX2-induced cell transformation and cancer progression in vivo was further augmented by HSP70. A positive correlation between HSP70 and AIMP2-DX2 levels was shown in various lung cancer cell lines and patient tissues. Chemical intervention in the AIMP2-DX2-HSP70 interaction suppressed cancer cell growth in vitro and in vivo. Thus, this work demonstrates the importance of the interaction between AIMP2-DX2 and HSP70 on tumor progression and its therapeutic potential against cancer.

Modeling stochastic processes in disease spread across a heterogeneous social system.

Diffusion processes are governed by external triggers and internal dynamics in complex systems. Timely and cost-effective control of infectious disease spread critically relies on uncovering underlying diffusion mechanisms, which is challenging due to invisible infection pathways and time-evolving intensity of infection cases. Here, we propose a new diffusion framework for stochastic processes, which models disease spread across metapopulations by incorporating human mobility as topological pathways in a heterogeneous social system. We apply Bayesian inference with the stochastic Expectation-Maximization algorithm to quantify underlying diffusion dynamics in terms of exogeneity and endogeneity and estimate cross-regional infection flow based on Granger causality. The effectiveness of our proposed model is shown by using comprehensive simulation procedures (robustness tests with noisy data considering missing or delayed human case reporting in real situations) and by applying the model to real data from 15-y dengue outbreaks in Australia.

Case Reports of Acute Transverse Myelitis Associated With mRNA Vaccine for COVID-19.

Acute transverse myelitis (ATM) has been reported as rare complication of vaccination. Herein, we report 2 cases of ATM after the administration of an mRNA vaccine for coronavirus disease 2019 (COVID-19). The first one is an 81-year-old man who received the BNT162b2 vaccine. He presented with bilateral hand weakness. Spine magnetic resonance imaging (MRI) showed high signal intensity from the C1 to C3 vertebrae. The second is a 23-year-old woman who received the BNT162b2 vaccine and experienced tingling in her legs. Spine MRI showed a high signal intensity lesion at the conus medullaris. These patients were treated with intravenous methylprednisolone and their symptoms improved slightly. Careful follow-up is needed to identify adverse events after the administration of mRNA vaccines for COVID-19.

LPS-induced epithelial barrier disruption via hyperactivation of CACC and ENaC.

Gram-negative bacterial lipopolysaccharide (LPS) increases the susceptibility of cells to pathogenic diseases, including inflammatory diseases and septic syndrome. In our experiments, we examined whether LPS induces epithelial barrier disruption in secretory epithelia and further investigated its underlying mechanism. The activities of Ca2+-activated Cl- channels (CACC) and epithelial Na+ channels (ENaC) were monitored with a short-circuit current using an Ussing chamber. Epithelial membrane integrity was estimated via transepithelial electrical resistance and paracellular permeability assays. We found that the apical application of LPS evoked short-circuit current (Isc) through the activation of CACC and ENaC. Although LPS disrupted epithelial barrier integrity, this was restored with the inhibition of CACC and ENaC, indicating the role of CACC and ENaC in the regulation of paracellular pathways. We confirmed that LPS, CACC, or ENaC activation evoked apical membrane depolarization. The exposure to a high-K+ buffer increased paracellular permeability. LPS induced the rapid redistribution of zonula occludens-1 (ZO-1) and reduced the expression levels of ZO-1 in tight junctions through apical membrane depolarization and tyrosine phosphorylation. However, the LPS-induced epithelial barrier disruption and degradation of ZO-1 were largely recovered by blocking CACC and ENaC. Furthermore, although LPS-impaired epithelial barrier became vulnerable to secondary bacterial infections, this vulnerability was prevented by inhibiting CACC and ENaC. We concluded that LPS induces the disruption of epithelial barrier integrity through the activation of CACC and ENaC, resulting in apical membrane depolarization and the subsequent tyrosine phosphorylation of ZO-1.

Allosteric Inhibition of the Tumor-Promoting Interaction Between Exon 2-Depleted Splice Variant of Aminoacyl-Transfer RNA Synthetase-Interacting Multifunctional Protein 2 and Heat Shock Protein 70.

Although protein-protein interactions (PPIs) have emerged as an attractive therapeutic target space, the identification of chemicals that effectively inhibit PPIs remains challenging. Here, we identified through library screening a chemical probe (compound 1) that can inhibit the tumor-promoting interaction between the oncogenic factor exon 2-depleted splice variant of aminoacyl-transfer RNA synthetase-interacting multifunctional protein 2 (AIMP2-DX2) and heat shock protein 70 (HSP70). We found that compound 1 binds to the N-terminal subdomain of glutathione S-transferase (GST-N) of AIMP2-DX2, causing a direct steric clash with HSP70 and an intramolecular interaction between the N-terminal flexible region and the GST-N of AIMP2-DX2, which induces masking of the HSP70 binding region during molecular dynamics and mutation studies. Compound 1 thus interferes with the AIMP2-DX2 and HSP70 interaction and suppresses the growth of cancer cells that express high levels of AIMP2-DX2 in vitro and in preliminary in vivo experiment. This work provides an example showing that allosteric conformational changes induced by chemicals can be a way to control pathologic PPIs. SIGNIFICANCE STATEMENT: Compound 1 is a promising protein-protein interaction inhibitor between AIMP2-DX2 and HSP70 for cancer therapy by the mechanism with allosteric modulation as well as competitive binding. It seems to induce allosteric conformational change of AIMP2-DX2 proteins and direct binding clash between AIMP2-DX2 and HSP70. The compound reduced the level of AIMP2-DX2 in ubiquitin-dependent manner via suppression of binding between AIMP2-DX2 and HSP70 and suppressed the growth of cancer cells highly expressing AIMP2-DX2 in vitro and in preliminary in vivo experiment.

Bisphosphonate-Conjugated Photo-Crosslinking Polyanionic Hyaluronic Acid Microbeads for Controlled BMP2 Delivery and Enhanced Bone Formation Efficacy.

In this study, we designed bisphosphonate-conjugated polyanionic hyaluronic acid (HA) microbeads (MBs) for the controlled delivery of bone morphogenetic protein 2 (BMP2). MBs were prepared via the photo-crosslinking of bisphosphonate (alendronate)-conjugated methacrylated HA (Alen-MHA). The polyanionic Alen-MHA MBs actively absorbed cationic BMP2 up to 91.0% of the loading efficacy and displayed a sustained release of BMP2 for 10 days. BMP2/Alen-MHA MBs induced osteogenic-related genes in cellular experiments and showed the highly increased bone formation efficacy in thigh muscle injection and rat spinal fusion animal models. Thus, BMP2/Alen-MHA MBs provide a promising opportunity to improve the delivery efficiency of BMP2.

Increased Histone Acetylation and Decreased Expression of Specific Histone Deacetylases in Ultraviolet-Irradiated and Intrinsically Aged Human Skin In Vivo.

Histone deacetylases (HDACs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins and play a crucial role in epigenetic regulation. Previously, we showed that histone acetylation is implicated in ultraviolet (UV)-induced inflammation and matrix impairment. To elucidate the histone acetylation status and specific HDACs involved in skin aging, we examined the changes in histone acetylation, global HDAC activity, and the expression of HDACs and sirtuins (SIRTs) in intrinsically aged and photoaged human skin as well as in UV-irradiated human skin in vivo. Following acute UV irradiation, the acetylated histone H3 (AcH3) level was increased, but HDAC activity and the expression levels of HDAC4, HDAC11, and SIRT4 were significantly decreased. In intrinsically aged skin, AcH3 levels were increased, but HDAC activity and the expression levels of HDAC4, HDAC5, HDAC10, HDAC11, SIRT6, and SIRT7 were significantly decreased. However, histone acetylation and HDAC expression in photoaged skin were not significantly different from those in intrinsically aged skin. Collectively, HDAC4 and HDAC11 were decreased in both UV-irradiated and intrinsically aged skin, suggesting that they may play a universal role in increased histone acetylation associated with skin aging.

Soft tissue expander for vertically atrophied alveolar ridges: Prospective, multicenter, randomized controlled trial.

OBJECTIVES: Conventional guided bone regeneration (GBR) limits the amount of bone graft due to limited soft tissue expansion. We hypothesize that the use of tissue expander will successfully augment soft tissue prior to bone graft, allowing for sufficient amount of grafting which will lead to a more stable and effective vertical bone graft. The authors aimed to evaluate effectiveness of the novel self-inflating tissue expander for vertical augmentation in terms of soft tissue expansion, clinical outcomes, and related complications. MATERIAL AND METHODS: A prospective, multicenter, randomized controlled trial was performed on patients requiring vertical augmentation. For experimental group patients, the tissue expander was subperiosteally implanted and followed by a tunneling bone graft without full flap reflection. Control patients underwent conventional vertical GBR. Primary objectives were to evaluate the dimensional changes of soft tissue and radiographic vertical bone gain and retention. As a secondary outcome, clinical complications and thickness changes of expanded overlying tissue were assessed and analyzed. RESULTS: Twenty-three patients in each group were included. During a 4-week expansion, two of the experimental group showed over-expansion and one showed mucosal perforation associated with previous severe scars. The other patients showed uneventful expansion and mean tissue augmentation was 6.88 ± 1.64 mm vertically. Ultrasonographic measurements of overlying gingiva revealed no thinning after tissue expansion (p > .05). Significantly higher vertical bone gain was shown in the experimental group (5.12 ± 1.25 mm) compared with that in the control patients (4.22 ± 1.15 mm; p < .05). After a 6-month retention period, the mean vertical bone measurement of the controls had decreased to 1.90 mm (55.0% reduction), which was a significantly greater decrease than that in the experimental group (mean 3.55 mm, 30.7% reduction; p < .05). CONCLUSION: Our results demonstrated the effectiveness of tissue expanders followed by tunneling bone graft for vertical augmentation; however, studies comparing the two techniques without tissue expanders are needed to elucidate the net effect of tissue expansion.

Pharmacokinetic study of two extended-release formulations of cilostazol in healthy Korean subjects: A randomized, open-label, multiple-dose, two-period crossover study
.

OBJECTIVES: The aim of this study was to compare the pharmacokinetic characteristics and safety of two extended-release formulations of cilostazol after multiple oral doses in healthy Korean subjects. MATERIALS AND METHODS: A randomized, open-label, multiple-dose, two-period, crossover study was conducted in 30 healthy male subjects. In each treatment period, subjects received oral doses of 200 mg cilostazol SR (Pletaal SR Cap.) or cilostazol CR (Cilostan CR Tab.) once daily for 5 consecutive days, with a washout period of 9 days. Plasma concentrations of cilostazol and its metabolites were determined using a validated liquid chromatography-tandem mass spectrometry method. RESULTS: 24 subjects completed the study. The maximum plasma concentrations (Cmax,ss, geometric mean (geometric coefficient of variation, CV%)) of cilostazol after cilostazol SR and cilostazol CR regimens were 1,532.7 (43.2%) ng/mL and 548.3 (58.9%) ng/mL, respectively, and the areas under the plasma concentration-time curves within dosing intervals (AUCτ, geometric mean (CV%)) were 17,060.7 (39.2%) h×ng/mL and 7,485.7 (55.0%) h×ng/mL, respectively. The geometric mean ratios (cilostazol SR/cilostazol CR) of the Cmax,ss and AUCτ values were 2.7954 (90% confidence interval: 2.3561 - 3.3166) and 2.2791 (90% confidence interval: 1.9770 - 2.6273), respectively. Both cilostazol SR and cilostazol CR were well tolerated in all subjects, and no serious adverse events occurred. The total incidence of headache, which is the most common adverse drug reaction, was significantly higher with cilostazol SR (63.0%) than cilostazol CR (25.9%). CONCLUSION: Cilostazol SR showed significantly higher Cmax and AUCτ of cilostazol than cilostazol CR after 5 days of multiple dosing of extended-release formulations of cilostazol.

The effect of scanning distance on the accuracy of intra-oral scanners used in dentistry.

The aim of this study was to evaluate the factors affecting intra-oral scanner accuracy by analyzing variation in measurements of a dental model according to scanning distance. A dental cast, including a prepared left mandibular first molar, was used. Rectangular frames measuring 20 × 30 mm with heights of 2.5, 5.0, and 7.5 mm were made. The model was scanned 10 times with a reference scanner to obtain the true value. Scanning was performed 10 times at four distances of 0, 2.5, 5.0, and 7.5 mm with the frame of each height using the following intra-oral scanners: TRIOS; CS 3500; and PlanScan. In the linear distance measurement method (2D), measurements were taken at five parameters using the Rapidform software. In the best-fit alignment method (3D), using the Geomagic Control X, the root mean square values of the two scan images were calculated. In the 2D comparison, the different from the reference value was the smallest at 2.5 and 5.0 mm. In the 3D comparison, 2.5 and 5.0 mm were the most accurate, and 0 mm was the least accurate among the four distances. To the best of our knowledge, this study was the first to evaluate the accuracy of scanning distances, and found a difference between the accuracy of the scanning distance and the accuracy of the scanner. Moreover, the results of this study indicated that the scanning distance was a variable affecting accuracy. Clin. Anat. 32:430-438, 2019. © 2019 Wiley Periodicals, Inc.

Ramalin, an antioxidant compound derived from Antarctic lichen, prevents progression of liver fibrosis induced by dimethylnitrosamine (DNM) in rats.

Hepatic fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM), primarily collagen, within the liver. Because reactive oxygen species (ROS) has been implicated in its pathogenesis, the use of antioxidants as a potential treatment has been broadly explored. Here, we investigated the hepatoprotective properties of ramalin (RM), a compound extracted from the Antarctic lichen Ramalina terebrata, against hepatic fibrosis in vitro and in vivo. RM suppressed hepatic stellate cell (HSC) activation in vitro without any significant signs of adverse effects on the cells tested, and the accumulation of ECM was dramatically reduced in the liver tissue. Oral administration of RM in rats noticeably improved the gross appearance of the liver with increased body and liver weight relative to the DMN injected rats, and all of the serum biochemical markers returned to the normal range. RM treatment have ameliorated hepatic fibrosis in rats induced by DMN by repressing α-smooth muscle actin (α-SMA) and upregulating heme oxygenase-1 (HO-1). In addition, RM significantly reduced collagen accumulation, and levels of malondialdehyde (MDA) and hydroxyproline (HP) in the liver tissue of DMN injected rats. The efficacy exerted by RM was through erythroid 2-related factor 2 (Nrf2) mediated antioxidant response proteins such as HO-1 and NAD(P)H quinone dehydrogenase 1 (NQO-1). Our results show the beneficial effect of RM against the progression of hepatic fibrosis.

Relationship between burnout and PTSD symptoms in firefighters: the moderating effects of a sense of calling to firefighting.

PURPOSE: Firefighting has been reported to lead to burnout and posttraumatic stress disorder (PTSD). However, burnout and PTSD symptoms may vary depending on personal characteristics, such as having a sense of calling. This study examined the role of calling in the association between burnout and PTSD symptoms. We hypothesized that burnout would be associated with more severe PTSD symptoms and calling would buffer the relationship between burnout and PTSD symptoms. METHODS: The Korean version of the Maslach Burnout Inventory-General Survey, Sense of Calling Subscale of the Professionalism Scale, and the Impact of Event Scale-Revised-Korean version were used to measure burnout, calling, and PTSD symptoms. Data from 109 of 127 firefighters from Gyeonggi-do, South Korea were analyzed using hierarchical linear regression. RESULTS: Burnout was a significant predictor of PTSD symptoms. Furthermore, the interaction term between burnout and calling accounted for a significant variance in PTSD symptoms. Higher burnout was associated with severe PTSD symptoms, but this relationship differed by the level of calling. The increase in PTSD symptoms due to increased burnout in the high calling group was relatively higher than in the low and average calling groups. CONCLUSIONS: Calling, though perceived as a positive variable, can be hazardous to exhausted people. A sense of calling as part of one's job identity should not be encouraged until personal circumstances and characteristics, such burnout symptoms, are evaluated. Identifying context and variables associated with PTSD for interventions with firefighters and persons in other dangerous occupations should aid in their recovery from trauma exposure.

Retrospective Genetic Analysis of 200 Cases of Sudden Infant Death Syndrome and Its Relationship with Long QT Syndrome in Korea.

BACKGROUND: There has been a campaign by the National Education on Sleeping Habits and Living Environment, to reduce the incidence of sudden infant death syndrome (SIDS). However, more than 100 infants die suddenly and unexplainably before the age of 1 year in Korea. Long QT syndrome (LQTS), an inheritable cardiac disease, has been reported to likely be associated with up to 14% of SIDS cases. However, genetic studies of the association between SIDS and LQTS have not yet been conducted in Korea. METHODS: We conducted genetic analysis using genomic DNA extracted from paraffin-embedded tissue blocks from 200 SIDS cases autopsied between 2005 and 2013. We analyzed the following genetic mutations associated with LQTS, KCNQ1, SCN5A, KCNE1, KCNE2, KCNJ2, and CAV3. RESULTS: Of the 200 SIDS cases, 58% involved male infants (116 male and 84 female infants, respectively), the mean age was 140 days (median, 107 days; range, 24-270 days), and they were all of Asian-Korean ethnicity. SIDS IA category criteria comprised 45 cases (22.5%) while the rest were SIDS IB. Fifteen infants (7.5%) had R1193Q in SCN5A, of doubtful pathogenicity, and no pathogenic LQTS variants were observed. CONCLUSION: This genetic investigation of LQTS in SIDS showed a low diagnostic yield. These findings suggest that LQTS molecular autopsy could be cautiously conducted in selected cases with family involvement to improve the available genetic counseling information. Meanwhile, a national SIDS registry should be established to document and evaluate the genetic risk of SIDS in Korea.