Automatically Diagnosing Skull Fractures Using an Object Detection Method and Deep Learning Algorithm in Plain Radiography Images

Objective@#: Deep learning is a machine learning approach based on artificial neural network training, and object detection algorithm using deep learning is used as the most powerful tool in image analysis. We analyzed and evaluated the diagnostic performance of a deep learning algorithm to identify skull fractures in plain radiographic images and investigated its clinical applicability. @*Methods@#: A total of 2026 plain radiographic images of the skull (fracture, 991; normal, 1035) were obtained from 741 patients. The RetinaNet architecture was used as a deep learning model. Precision, recall, and average precision were measured to evaluate the deep learning algorithm’s diagnostic performance. @*Results@#: In ResNet-152, the average precision for intersection over union (IOU) 0.1, 0.3, and 0.5, were 0.7240, 0.6698, and 0.3687, respectively. When the intersection over union (IOU) and confidence threshold were 0.1, the precision was 0.7292, and the recall was 0.7650. When the IOU threshold was 0.1, and the confidence threshold was 0.6, the true and false rates were 82.9% and 17.1%, respectively. There were significant differences in the true/false and false-positive/false-negative ratios between the anteriorposterior, towne, and both lateral views (p=0.032 and p=0.003). Objects detected in false positives had vascular grooves and suture lines. In false negatives, the detection performance of the diastatic fractures, fractures crossing the suture line, and fractures around the vascular grooves and orbit was poor. @*Conclusion@#: The object detection algorithm applied with deep learning is expected to be a valuable tool in diagnosing skull fractures.

Comparison of Outcomes at Trauma Centers versus Non-Trauma Centers for Severe Traumatic Brain Injury

Objective@#: Traumatic brain injury (TBI) is one of the most common injuries in patients with multiple trauma, and it associates with high post-traumatic mortality and morbidity. A trauma center was established to provide optimal treatment for patients with severe trauma. This study aimed to compare the treatment outcomes of patients with severe TBI between non-trauma and trauma centers based on data from the Korean Neuro-Trauma Data Bank System (KNTDBS). @*Methods@#: From January 2018 to June 2021, 1122 patients were enrolled in the KNTDBS study. Among them, 253 patients from non-traumatic centers and 253 from trauma centers were matched using propensity score analysis. We evaluated baseline characteristics, the time required from injury to hospital arrival, surgery-related factors, neuromonitoring, and outcomes. @*Results@#: The time from injury to hospital arrival was shorter in the non-trauma centers (110.2 vs. 176.1 minutes, p=0.012). The operation time was shorter in the trauma centers (156.7 vs. 128.1 minutes, p0.003). Neuromonitoring was performed in nine patients (3.6%) in the non-trauma centers and 67 patients (26.5%) in the trauma centers (p<0.001). Mortality rates were lower in trauma centers than in non-trauma centers (58.5% vs. 47.0%, p=0.014). The average Glasgow coma scale (GCS) at discharge was higher in the trauma centers (4.3 vs. 5.7, p=0.011). For the Glasgow outcome scale-extended (GOSE) at discharge, the favorable outcome (GOSE 5–8) was 17.4% in the non-trauma centers and 27.3% in the trauma centers (p=0.014). @*Conclusion@#: This study showed lower mortality rates, higher GCS scores at discharge, and higher rates of favorable outcomes in trauma centers than in non-trauma centers. The regional trauma medical system seems to have a positive impact in treating patients with severe TBI.

Treatment Outcome of the Brain Metastases in Peri-Rolandic Area: Comparison Between Surgery and Stereotactic Radiosurgery

Background@#Brain metastases of peri-Rolandic area is crucial as it directly impacts the quality of life for cancer patients. Surgery or stereotactic radiosurgery (SRS) is considered for peri-Rolandic brain metastases as for other brain metastases. However, the benefit of each treatment modality on functional outcome has not been clearly defined for this tumor. The purpose of this study is to compare the functional course of each treatment and to suggest an effective treatment for patients’ quality of life. @*Methods@#Fifty-two patients who had undergone SRS or surgery for brain metastasis confirmedby enhanced MRI were enrolled retrospectively. Overall survival (OS), progression free survival (PFS), and functional outcomes were estimated using the Kaplan-Meier method, univariate, multivariate analysis, and Cox proportional hazards regression. @*Results@#Median OS and PFS were 13.3 months and 8.9 months in our study population.Treatment modalities were not significant factors for OS and PFS. Extracranial systemic cancer progression was significant factor for both parameters (p=0.030 for OS and p=0.040 for PFS). Median symptom improvement (improvement of at least 1 grade after surgery compared to preoperative state) time was significantly shorter in surgery group than in the SRS group (10.5 days vs. 37.5 days, p=0.034). @*Conclusion@#Surgery for brain metastases can contribute to a positive quality of life for the remain-ing duration of the patient’s life.

Full-Endoscopic versus Minimally Invasive Lumbar Interbody Fusion for Lumbar Degenerative Diseases : A Systematic Review and Meta-Analysis

Objective@#: Although full-endoscopic lumbar interbody fusion (Endo-LIF) has been tried as the latest alternative technique to minimally invasive transforaminal lumbar interobody fusion (MIS-TLIF) since mid-2010, the evidence is still lacking. We compared the clinical outcome and safety of Endo-LIF to MIS-TLIF for lumbar degenerative disease. @*Methods@#: We systematically searched electronic databases, including PubMed, EMBASE, and Cochrane Library to find literature comparing Endo-LIF to MIS-TLIF. The results retrieved were last updated on December 11, 2020. The perioperative outcome included the operation time, blood loss, complication, and hospital stay. The clinical outcomes included Visual analog scale (VAS) of low back pain and leg pain and Oswestry disability index (ODI), and the radiological outcome included pseudoarthosis rate with 12-month minimum follow-up. @*Results@#: Four retrospective observational studies and one prospective observational study comprising 423 patients (183 Endo-LIF and 241 MIS-TLIF) were included, and the pooled data analysis revealed low heterogeneity between studies in our review. Baseline characteristics including age and sex were not different between the two groups. Operation time was significantly longer in Endo- LIF (mean difference [MD], 23.220 minutes; 95% confidence interval [CI], 10.669–35.771; p=0.001). However, Endo-LIF resulted in less perioperative blood loss (MD, -144.710 mL; 95% CI, 247.941–41.478; p=0.023). Although VAS back pain at final (MD, -0.120; p=0.586), leg pain within 2 weeks (MD, 0.005; p=0.293), VAS leg pain at final (MD, 0.099; p=0.099), ODI at final (MD, 0.141; p=0.093) were not different, VAS back pain within 2 weeks was more favorable in the Endo-LIF (MD, -1.538; 95% CI, -2.044 to -1.032; p<0.001). On the other hand, no statistically significant group difference in complication rate (relative risk [RR], 0.709; p=0.774), hospital stay (MD, -2.399; p=0.151), and pseudoarthrosis rate (RR, 1.284; p=0.736) were found. @*Conclusion@#: Relative to MIS-TLIF, immediate outcomes were favorable in Endo-LIF in terms of blood loss and immediate VAS back pain, although complication rate, mid-term clinical outcomes, and fusion rate were not different. However, the challenges for Endo-LIF include longer operation time which means a difficult learning curve and limited surgical indication which means patient selection bias. Larger-scale, well-designed study with long-term follow-up and randomized controlled trials are needed to confirm and update the results of this systematic review.

The Relationship Between Trauma Scoring Systems and Outcomes in Patients With Severe Traumatic Brain Injury / 대한신경손상학회지

Objective@#This study investigated the relationship between trauma scoring systems and outcomes in patients with severe traumatic brain injury (TBI). @*Methods@#From January 2018 to June 2021, 1,122 patients with severe TBI were registered in the Korean Neuro-Trauma Data Bank System. Among them, 697 patients with data on trauma scoring systems were included in the study. According to the Glasgow Outcome Scale-Extended score, the patients were divided into unfavorable and favorable outcome groups. The abbreviated injury scale (AIS), injury severity score (ISS), revised trauma score (RTS), and trauma and injury severity score (TRISS) were evaluated. @*Results@#The AIS head score was higher in the unfavorable outcome group than in the favorable outcome group (4.39 vs. 4.06, p<0.001). ISS was also higher in the unfavorable outcome group (27.27 vs. 24.22, p=0.001). The RTS and TRISS were higher in the favorable outcome group (RTS, 4.74 vs. 5.45, p<0.001; TRISS, 48.05 vs. 71.02, p<0.001). In comparing the survival and death groups, the ISS was lower in the survival group (25.76 vs. 27.29, p=0.036). Furthermore, RTS was higher in the survival group (5.26 vs. 4.54, p<0.001), as was TRISS (62.11 vs. 44.91, p<0.001). @*Conclusion@#Trauma scoring systems, including ISS, RTS, and TRISS, provide tools for quantifying posttraumatic risk and can be used to predict prognosis. Among these, TRISS is an indicator of the predicted survival rate and is considered a clinically useful tool for predicting unfavorable and favorable outcomes in patients with severe TBI.

Developmental Delay and Rehabilitation in an Infant with Partial Trisomy 1q32.1 to 1q44: A Case Report

Partial trisomy 1q is a rare chromosomal disorder characterized by ventriculomegaly with craniofacial, renal, cardiac, and finger and toe anomalies. Most reported cases of partial trisomy1q have involved stillborn or premature deaths due to cardiac or liver failure. This case report describes an 18-month-old patient with partial duplication of the 1q32-44 segments and consequent developmental delays who exhibited improvement in developmental status with rehabilitation. Prenatal ultrasonography and magnetic resonance imaging of the mother revealed ventriculomegaly and atrophic changes in the left cerebral hemisphere of the fetus. The infant was born with micrognathia, microphthalmia, macrocephaly, low-set ears, polydactyly, and long feet at 37+5 weeks of gestation. A chromosomal study revealed an abnormal male karyotype of 46,XY,rec(1)dup(1)(q32.1q44)inv(1)(p36.3q32.1)pat. In this rare case of a patient with partial trisomy, we observed improvement in developmental delays following treatment using appropriate rehabilitation techniques. Further research is required to help validate the findings of this case study and establish a standardized rehabilitation technique that can be subsequently applied to such cases.

Flos magnoliae constituent fargesin has an anti-allergic effect via ORAI1 channel inhibition

Flos magnoliae (FM), the dry flower buds of Magnolia officinalis or its related species, is a traditional herbal medicine commonly used in Asia for symptomatic relief of and treating allergic rhinitis, headache, and sinusitis. Although several studies have reported the effects of FM on store-operated calcium entry (SOCE) via the ORAI1 channel, which is essential during intracellular calcium signaling cascade generation for T cell activation and mast cell degranulation, the effects of its isolated constituents on SOCE remain unidentified. Therefore, we investigated which of the five major constituents of 30% ethanoic FM (vanillic acid, tiliroside, eudesmin, magnolin, and fargesin) inhibit SOCE and their physiological effects on immune cells. The conventional whole-cell patch clamp results showed that fargesin, magnolin, and eudesmin significantly inhibited SOCE and thus human primary CD4 + T lymphocyte proliferation, as well as allergen-induced histamine release in mast cells. Among them, fargesin demonstrated the most potent inhibitory effects not only on ORAI1 (IC 50 = 12.46 ± 1.300 μM) but also on T-cell proliferation (by 87.74% ± 1.835%) and mast cell degranulation (by 20.11% ± 5.366%) at 100 μM. Our findings suggest that fargesin can be a promising candidate for the development of therapeutic drugs to treat allergic diseases.

Nootkatol prevents ultraviolet radiation-induced photoaging via ORAI1 and TRPV1 inhibition in melanocytes and keratinocytes

Skin photoaging occurs due to chronic exposure to solar ultraviolet radiation (UV), the main factor contributing to extrinsic skin aging. Clinical signs of photoaging include the formation of deep, coarse skin wrinkles and hyperpigmentation.Although melanogenesis and skin wrinkling occur in different skin cells and have different underlying mechanisms, their initiation involves intracellular calcium signaling via calcium ion channels. The ORAI1 channel initiates melanogenesis in melanocytes, and the TRPV1 channel initiates MMP-1 production in keratinocytes in response to UV stimulation. We aimed to develop a drug that may simultaneously inhibit ORAI1 and TRPV1 activity to help prevent photoaging. We synthesized nootkatol, a chemical derivative of valencene. TRPV1 and ORAI1 activities were measured using the whole-cell patch-clamp technique. Intracellular calcium concentration [Ca2+ ] i was measured using calcium-sensitive fluorescent dye (Fura-2 AM). UV-induced melanin formation and MMP-1 production were quantified in B16F10 melanoma cells and HaCaT cells, respectively. Our results indicate that nootkatol (90 μM) reduced TRPV1 current by 94% ± 2% at –60 mV and ORAI1 current by 97% ± 1% at –120 mV. Intracellular calcium signaling was significantly inhibited by nootkatol in response to ORAI1 activation in human primary melanocytes (51.6% ± 0.98% at 100 μM). Additionally, UV-induced melanin synthesis was reduced by 76.38% ± 5.90% in B16F10 melanoma cells, and UV-induced MMP-1 production was reduced by 59.33% ± 1.49% in HaCaT cells. In conclusion, nootkatol inhibits both TRPV1 and ORAI1 to prevent photoaging, and targeting ion channels may be a promising strategy for preventing photoaging.

Flos magnoliae constituent fargesin has an anti-allergic effect via ORAI1 channel inhibition

Flos magnoliae (FM), the dry flower buds of Magnolia officinalis or its related species, is a traditional herbal medicine commonly used in Asia for symptomatic relief of and treating allergic rhinitis, headache, and sinusitis. Although several studies have reported the effects of FM on store-operated calcium entry (SOCE) via the ORAI1 channel, which is essential during intracellular calcium signaling cascade generation for T cell activation and mast cell degranulation, the effects of its isolated constituents on SOCE remain unidentified. Therefore, we investigated which of the five major constituents of 30% ethanoic FM (vanillic acid, tiliroside, eudesmin, magnolin, and fargesin) inhibit SOCE and their physiological effects on immune cells. The conventional whole-cell patch clamp results showed that fargesin, magnolin, and eudesmin significantly inhibited SOCE and thus human primary CD4 + T lymphocyte proliferation, as well as allergen-induced histamine release in mast cells. Among them, fargesin demonstrated the most potent inhibitory effects not only on ORAI1 (IC 50 = 12.46 ± 1.300 μM) but also on T-cell proliferation (by 87.74% ± 1.835%) and mast cell degranulation (by 20.11% ± 5.366%) at 100 μM. Our findings suggest that fargesin can be a promising candidate for the development of therapeutic drugs to treat allergic diseases.

Nootkatol prevents ultraviolet radiation-induced photoaging via ORAI1 and TRPV1 inhibition in melanocytes and keratinocytes

Skin photoaging occurs due to chronic exposure to solar ultraviolet radiation (UV), the main factor contributing to extrinsic skin aging. Clinical signs of photoaging include the formation of deep, coarse skin wrinkles and hyperpigmentation.Although melanogenesis and skin wrinkling occur in different skin cells and have different underlying mechanisms, their initiation involves intracellular calcium signaling via calcium ion channels. The ORAI1 channel initiates melanogenesis in melanocytes, and the TRPV1 channel initiates MMP-1 production in keratinocytes in response to UV stimulation. We aimed to develop a drug that may simultaneously inhibit ORAI1 and TRPV1 activity to help prevent photoaging. We synthesized nootkatol, a chemical derivative of valencene. TRPV1 and ORAI1 activities were measured using the whole-cell patch-clamp technique. Intracellular calcium concentration [Ca2+ ] i was measured using calcium-sensitive fluorescent dye (Fura-2 AM). UV-induced melanin formation and MMP-1 production were quantified in B16F10 melanoma cells and HaCaT cells, respectively. Our results indicate that nootkatol (90 μM) reduced TRPV1 current by 94% ± 2% at –60 mV and ORAI1 current by 97% ± 1% at –120 mV. Intracellular calcium signaling was significantly inhibited by nootkatol in response to ORAI1 activation in human primary melanocytes (51.6% ± 0.98% at 100 μM). Additionally, UV-induced melanin synthesis was reduced by 76.38% ± 5.90% in B16F10 melanoma cells, and UV-induced MMP-1 production was reduced by 59.33% ± 1.49% in HaCaT cells. In conclusion, nootkatol inhibits both TRPV1 and ORAI1 to prevent photoaging, and targeting ion channels may be a promising strategy for preventing photoaging.

Risk factors of postoperative remote intracerebral hemorrhage after craniotomy for ruptured cerebral aneurysms

Objective@#We aimed to identify the relation between perioperative cerebrospinal fluid (CSF) drain through lumbar drainage (LD) and development of postoperative (POP) remote intracerebral hemorrhage (rICH) in craniotomy to treat ruptured intracranial aneurysms. @*Methods@#We retrospectively reviewed consecutive patients who underwent craniotomy for ruptured cerebral aneurysms at the authors’ institution between 1998 and 2004. We subsequently compared the incidence and characteristics of POP rICH between the patients who had a perioperative LD and those who did not. All statistical analyses were conducted using the software package SPSS 19.0 (SPSS Inc., Chicago, IL, USA). A p value of <0.05 was considered statistically significant. @*Results@#We enrolled 688 patients, of which 80 patients (11.6%) received perioperative LD, and 608 did not. LD and non-LD groups were comparable because although clinical characteristics of the two groups were significantly different considering history of hypertension, timing of surgery, and closed system negative pressure suction drain (SD) placement, none of these three variables was an independent risk factor associated with POP rICH in multivariate analysis. POP rICH incidence was significantly higher in the LD goup (12.5%) than non-LD group (0.8%) (p=0.000) in univariate analysis. LD placement was the only independent risk factor associated with the development of rICH in multivariate logistic regression analysis. @*Conclusions@#POP rICH incidence was significantly higher in patients who were managed with perioperative LD than in those who did not. LD insertion in craniotomy for ruptured intracranial aneurysm, should be closely monitored to address the occurrence of POP rICH.

Associated Factors for Asthma Severity in Korean Children: A Korean Childhood Asthma Study

PURPOSE: Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. METHODS: This study was performed on 667 children aged 5–15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. RESULTS: Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. CONCLUSIONS: Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.

Luteolin reduces fluid hypersecretion by inhibiting TMEM16A in interleukin-4 treated Calu-3 airway epithelial cells

Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl– and HCO3 – is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calciumactivated Cl– channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SPEtOH- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

Gardenia jasminoides extract and its constituent, genipin, inhibit activation of CD3/CD28 co-stimulated CD4+ T cells via ORAI1 channel

Gardenia jasminoides (GJ) is a widely used herbal medicine with antiinflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJEtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJEtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJHEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJHEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited IORAI1 and interleukin-2 production in CD3/ CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4+ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

Does work time limit for resident physician affect short-term treatment outcome and hospital length of stay in patients with spontaneous intracerebral hemorrhage?: a two-year experience at a single training hospital in South Korea

Objective@#To compare short-term treatment outcomes at hospital discharge and hospital length of stay (LOS) in patients with spontaneous intracerebral hemorrhage (sICH) before and after introduction of resident physician work time limit (WTL). @*Methods@#We retrospectively reviewed consecutive patients treated for sICH at our institution between 2016 and 2019. Then we dichotomized these patients into two groups, pre-WTL and post-WTL. We analyzed demographic elements and clinical features, and hospital length of stay (LOS). We evaluated short-term outcome using modified Rankin scale score at hospital discharge and then divided it into “good” and “poor” outcome groups. We subsequently, compared short-term treatment outcome and hospital LOS between the pre-WTL and post-WTL groups. @*Results@#Out of 779 patients, 420 patients (53.9%) were included in the pre-WTL group, and 359 (46.1%) in post-WTL. The mortality rate in sICH patients was higher in the post-WTL group (pre-WTL; 13.6% vs. post-WTL; 17.3%), but there was no statistically significant difference in short-term outcome including mortality (p=0.332) between the groups. The LOS also, was not significantly different between the two groups (pre-WTL; 19.0 days vs. post-WTL; 20.2 days) (p=0.341). The initial Glasgow Coma Scale score, personal stroke history, and mean age were the only independent outcome predicting factors for patients with sICH. @*Conclusions@#Some neurosurgeons may expect poorer outcome for sICH after implementation of the WTL of the K-MHW for resident physician however, enforcement of the WTL did not significantly influence the short-term outcome and hospital LOS for sICH in our hospital. Further well-designed multi-institutional prospective studies on the effects of WTL in sICH patient outcome, are anticipated.

Luteolin reduces fluid hypersecretion by inhibiting TMEM16A in interleukin-4 treated Calu-3 airway epithelial cells

Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl– and HCO3 – is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calciumactivated Cl– channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SPEtOH- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

Gardenia jasminoides extract and its constituent, genipin, inhibit activation of CD3/CD28 co-stimulated CD4+ T cells via ORAI1 channel

Gardenia jasminoides (GJ) is a widely used herbal medicine with antiinflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJEtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJEtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJHEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJHEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited IORAI1 and interleukin-2 production in CD3/ CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4+ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

Does work time limit for resident physician affect short-term treatment outcome and hospital length of stay in patients with spontaneous intracerebral hemorrhage?: a two-year experience at a single training hospital in South Korea

Objective@#To compare short-term treatment outcomes at hospital discharge and hospital length of stay (LOS) in patients with spontaneous intracerebral hemorrhage (sICH) before and after introduction of resident physician work time limit (WTL). @*Methods@#We retrospectively reviewed consecutive patients treated for sICH at our institution between 2016 and 2019. Then we dichotomized these patients into two groups, pre-WTL and post-WTL. We analyzed demographic elements and clinical features, and hospital length of stay (LOS). We evaluated short-term outcome using modified Rankin scale score at hospital discharge and then divided it into “good” and “poor” outcome groups. We subsequently, compared short-term treatment outcome and hospital LOS between the pre-WTL and post-WTL groups. @*Results@#Out of 779 patients, 420 patients (53.9%) were included in the pre-WTL group, and 359 (46.1%) in post-WTL. The mortality rate in sICH patients was higher in the post-WTL group (pre-WTL; 13.6% vs. post-WTL; 17.3%), but there was no statistically significant difference in short-term outcome including mortality (p=0.332) between the groups. The LOS also, was not significantly different between the two groups (pre-WTL; 19.0 days vs. post-WTL; 20.2 days) (p=0.341). The initial Glasgow Coma Scale score, personal stroke history, and mean age were the only independent outcome predicting factors for patients with sICH. @*Conclusions@#Some neurosurgeons may expect poorer outcome for sICH after implementation of the WTL of the K-MHW for resident physician however, enforcement of the WTL did not significantly influence the short-term outcome and hospital LOS for sICH in our hospital. Further well-designed multi-institutional prospective studies on the effects of WTL in sICH patient outcome, are anticipated.

The Korean Version of the Test for Respiratory and Asthma Control in Kids (TRACK): Reliability and Validity

BACKGROUND: Test for Respiratory and Asthma Control in Kids (TRACK) questionnaires were developed and validated in various languages to monitor respiratory control in preschool-aged children. We aimed to assess the reliability and validity of the Korean version of the TRACK questionnaire. METHODS: We administered the linguistically validated TRACK questionnaires to caregivers of asthmatic preschool children on two separate visits 4–6 weeks apart. Each physician graded the level of the guideline-based asthma control, assessed the timing of symptoms, and adjusted the therapeutic level at each visit. RESULTS: A total of 137 children were enrolled in the study. Cronbach's alpha was 0.65 for a questionnaire as a whole. The test-retest reliability was 0.72. The median TRACK scores were significantly different between asthma control status categories, with the lowest scores in children classified as poorly controlled and the highest in the well-controlled group (P < 0.001). They were different among groups classified according to the physician adjusted therapeutic levels, with the lowest values in children prescribed step-up therapy (P < 0.001), and according to the recency of respiratory symptoms (P < 0.001). Finally, the changes in TRACK scores between visits were highest in subjects showing improved control, followed by unchanged, and worsened control. When we applied the traditional cut-off of 80 for a well-controlled condition, a sensitivity of 75.6% and a specificity of 70.9% were calculated. CONCLUSION: The Korean translated version of the TRACK questionnaire is valid and reliable to assess respiratory and asthma control in Korean preschool children with asthma symptoms.

Intraoperative Frozen Cytology of Central Nervous System Neoplasms: An Ancillary Tool for Frozen Diagnosis

BACKGROUND: Pathologic diagnosis of central nervous system (CNS) neoplasms is made by comparing light microscopic, immunohistochemical, and molecular cytogenetic findings with clinicoradiologic observations. Intraoperative frozen cytology smears can improve the diagnostic accuracy for CNS neoplasms. Here, we evaluate the diagnostic value of cytology in frozen diagnoses of CNS neoplasms. METHODS: Cases were selected from patients undergoing both frozen cytology and frozen sections. Diagnostic accuracy was evaluated. RESULTS: Four hundred and fifty-four cases were included in this retrospective single-center review study covering a span of 10 years. Five discrepant cases (1.1%) were found after excluding 53 deferred cases (31 cases of tentative diagnosis, 22 cases of inadequate frozen sampling). A total of 346 cases of complete concordance and 50 cases of partial concordance were classified as not discordant cases in the present study. Diagnostic accuracy of intraoperative frozen diagnosis was 87.2%, and the accuracy was 98.8% after excluding deferred cases. Discrepancies between frozen and permanent diagnoses (n = 5, 1.1%) were found in cases of nonrepresentative sampling (n = 2) and misinterpretation (n = 3). High concordance was observed more frequently in meningeal tumors (97/98, 99%), metastatic brain tumors (51/52, 98.1%), pituitary adenomas (86/89, 96.6%), schwannomas (45/47, 95.8%), high-grade astrocytic tumors (47/58, 81%), low grade astrocytic tumors (10/13, 76.9%), non-neoplastic lesions (23/36, 63.9%), in decreasing frequency. CONCLUSIONS: Using intraoperative cytology and frozen sections of CNS tumors is a highly accurate diagnostic ancillary method, providing subtyping of CNS neoplasms, especially in frequently encountered entities.