Ibulocydine Inhibits Migration and Invasion of TNBC Cells via MMP-9 Regulation.

Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancer types, indicating a poor survival prognosis with a more aggressive biology of metastasis to the lung and a short response duration to available therapies. Ibulocydine (IB) is a novel (cyclin-dependent kinase) CDK7/9 inhibitor prodrug displaying potent anti-cancer effects against various cancer cell types. We performed in vitro and in vivo experiments to determine whether IB inhibits metastasis and eventually overcomes the poor drug response in TNBC. The result showed that IB inhibited the growth of TNBC cells by inducing caspase-mediated apoptosis and blocking metastasis by reducing MMP-9 expression in vitro. Concurrently, in vivo experiments using the metastasis model showed that IB inhibited metastasis of MDA-MB-231-Luc cells to the lung. Collectively, these results demonstrate that IB inhibited the growth of TNBC cells and blocked metastasis by regulating MMP-9 expression, suggesting a novel therapeutic agent for metastatic TNBC.

Improving radiomics reproducibility using deep learning-based image conversion of CT reconstruction algorithms in hepatocellular carcinoma patients.

OBJECTIVES: CT reconstruction algorithms affect radiomics reproducibility. In this study, we evaluate the effect of deep learning-based image conversion on CT reconstruction algorithms. METHODS: This study included 78 hepatocellular carcinoma (HCC) patients who underwent four-phase liver CTs comprising non-contrast, late arterial (LAP), portal venous (PVP), and delayed phase (DP), reconstructed using both filtered back projection (FBP) and advanced modeled iterative reconstruction (ADMIRE). PVP images were used to train a convolutional neural network (CNN) model to convert images from FBP to ADMIRE and vice versa. LAP, PVP, and DP images were used for validation and testing. Radiomic features were extracted for each patient with a semi-automatic segmentation tool. We used concordance correlation coefficients (CCCs) to evaluate the radiomics reproducibility for original FBP (oFBP) vs. original ADMIRE (oADMIRE), oFBP vs. converted FBP (cFBP), and oADMIRE vs. converted ADMIRE (cADMIRE). RESULTS: In the test group including 30 patients, the CCC and proportion of reproducible features (CCC ≥ 0.85) for oFBP vs. oADMIRE were 0.65 and 32.9% (524/1595) for LAP, 0.65 and 35.9% (573/1595) for PVP, and 0.69 and 43.8% (699/1595) for DP. For oFBP vs. cFBP, the values increased to 0.92 and 83.9% (1339/1595) for LAP, 0.89 and 71.0% (1133/1595) for PVP, and 0.90 and 79.7% (1271/1595) for DP. Similarly, for oADMIRE vs. cADMIRE, the values increased to 0.87 and 68.1% (1086/1595) for LAP, 0.91 and 82.1% (1309/1595) for PVP, and 0.89 and 76.2% (1216/1595) for DP. CONCLUSIONS: CNN-based image conversion between CT reconstruction algorithms improved the radiomics reproducibility of HCCs. CLINICAL RELEVANCE STATEMENT: This study demonstrates that using a CNN-based image conversion technique significantly improves the reproducibility of radiomic features in HCCs, highlighting its potential for enhancing radiomics research in HCC patients. KEY POINTS: Radiomics reproducibility of HCC was improved via CNN-based image conversion between two different CT reconstruction algorithms. This is the first clinical study to demonstrate improvements across a range of radiomic features in HCC patients. This study promotes the reproducibility and generalizability of different CT reconstruction algorithms in radiomics research.

The effects of dietary self-monitoring intervention on anthropometric and metabolic changes via a mobile application or paper-based diary: a randomized trial.

BACKGROUND/OBJECTIVES: Weight loss via a mobile application (App) or a paper-based diary (Paper) may confer favorable metabolic and anthropometric changes. SUBJECTS/METHODS: A randomized parallel trial was conducted among 57 adults whose body mass indices (BMIs) were 25 kg/m2 or greater. Participants randomly assigned to either the App group (n = 30) or the Paper group (n = 27) were advised to record their foods and supplements through App or Paper during the 12-week intervention period. Relative changes of anthropometries and biomarker levels were compared between the 2 intervention groups. Untargeted metabolic profiling was identified to discriminate metabolic profiles. RESULTS: Out of the 57 participants, 54 participants completed the trial. Changes in body weight and BMI were not significantly different between the 2 groups (P = 0.11). However, body fat and low-density lipoprotein (LDL)-cholesterol levels increased in the App group but decreased in the Paper group, and the difference was statistically significant (P = 0.03 for body fat and 0.02 for LDL-cholesterol). In the metabolomics analysis, decreases in methylglyoxal and (S)-malate in pyruvate metabolism and phosphatidylcholine (lecithin) in linoleic acid metabolism from pre- to post-intervention were observed in the Paper group. CONCLUSIONS: In the 12-week randomized parallel trial of weight loss through a App or a Paper, we found no significant difference in change in BMI or weight between the App and Paper groups, but improvement in body fatness and LDL-cholesterol levels only in the Paper group under the circumstances with minimal contact by dietitians or health care providers. Trial Registration: Clinical Research Information Service Identifier: KCT0004226.

Intractable chylous leak after radical esophagectomy treated with radiotherapy.

Postoperative chylous leak after esophagectomy is a rare but potentially life-threatening complication that results in hypovolemia, electrolyte imbalance, malnutrition, and immunologic deficiency. However, the management of postoperative chylous leak remains controversial. Following a diagnosis of esophageal cancer, a 64-year-old man was treated by video-assisted thoracoscopic esophagectomy, laparoscopic gastric tube formation, prophylactically thoracic duct ligation, and reconstruction with esophagogastrostomy at the neck level. Massive postoperative drainage from the thorax and abdomen did not initially meet the diagnostic criteria for chylothorax, which was ultimately diagnosed 3 weeks after the operation. Despite various treatments including total parenteral nutrition, octreotide and midodrine, reoperation (thoracic duct ligation and mechanical pleurodesis), and thoracic duct embolization, the chylous leak persisted. Finally, low-dose radiation therapy was administered with a daily dose of 2 Gy and completed at a total dose of 14 Gy. After this, the amount of pleural effusion gradually decreased over 2 weeks, and the last drainage tube was removed. The patient was alive and well at 60 months postoperatively. Herein, we describe a patient with intractable chylous leak after esophagectomy, which persisted despite conservative treatment, thoracic duct ligation, and embolization, but was finally successfully treated with radiotherapy.

Associations Between Headache (Migraine and Tension-Type Headache) and Psychological Symptoms (Depression and Anxiety) in Pediatrics: A Systematic Review and Meta-analysis.

BACKGROUND: There have been no recent meta-analysis studies on specific psychological symptoms (depression and anxiety) according to the type of primary headache disorder in children and adolescents. OBJECTIVES: We performed a meta-analysis of various psychodiagnostic scales. Psychological symptoms of primary headache disorders have been reported in previous studies. STUDY DESIGN: A systematic review and meta-analysis. METHODS: We conducted systematic reviews using the PubMed, Embase, Cochrane Library, and Scopus databases up to October 19, 2022. Ten studies were selected by applying the inclusion criteria. The psychological symptoms (depression and anxiety) of children and adolescents with migraine and tension-type headache (TTH) were compared with those of healthy controls using scale scores. All statistical analyses of the pooled data were performed using RevMan 5.3 software. RESULTS: Psychodiagnostic tools to assess depression scored higher in patients with migraine than in healthy controls; however, most anxiety-related scores were not significantly different between the migraine and control groups. In contrast, anxiety-related scores were higher in patients with TTH than in healthy controls, but the score to measure the degree of depressive symptoms was not significantly different from the control group in patients with TTH. LIMITATIONS: A limited number of studies for each scale were included. In addition, each scale has different sensitivities and specificities, which may have affected the results. In addition, we did not evaluate the differences in psychological symptoms according to the frequency and severity of headaches. CONCLUSIONS: Depression is more associated with migraine; whereas, anxiety is more associated with TTH than healthy controls. Therefore, the screening and assessment of psychological symptoms should be performed in children and adolescents with primary headache disorders.

miR-199a and miR-199b facilitate diffuse gastric cancer progression by targeting Frizzled-6.

Pathological markers that can monitor the progression of gastric cancer (GC) may facilitate the diagnosis and treatment of patients with diffuse GC (DGC). To identify microRNAs (miRNAs) that can differentiate between early and advanced DGC in the gastric mucosa, miRNA expression profiling was performed using the NanoString nCounter method in human DGC tumors. Ectopic expression of miR-199a and miR-199b (miR-199a/b) in SNU601 human GC cells accelerated the growth rate, viability, and motility of cancer cells and increased the tumor volume and weight in a mouse xenograft model. To study their clinicopathological roles in patients with GC, miR-199a/b levels were measured in human GC tumor samples using in situ hybridization. High miR-199a/b expression level was associated with enhanced lymphovascular invasion, advanced T stage, and lymph-node metastasis. Using the 3'-untranslated region (UTR) luciferase assay, Frizzled-6 (FZD6) was confirmed to be a direct target of miR-199a/b in GC cells. siRNA-mediated depletion of FZD6 enhanced the motility of SNU601 cells, and addback of FZD6 restored cancer cell motility stimulated by miR-199a/b. In conclusion, miR-199a/b promotes DGC progression by targeting FZD6, implying that miR-199a/b can be used as prognostic and diagnostic biomarkers for the disease.

Large mesenchymal cystic and chondroid pulmonary hamartoma mimicking lung cancer: Case report.

Pulmonary hamartoma is the most commonly resected benign neoplasm of lung. The mesenchymal cystic subtype is a rare and often bilaterally occurring variant composed of multiple cysts and nodules. Herein, we present an asymptomatic 70-year-old woman with a large and mostly cystic growth of right hilar region. Computed tomography of the chest and fluorodeoxyglucose positron emission tomography/computed tomography imaging traced its origins to right middle lobe. Overall features suggested primary lung cancer or perhaps other cystic lung disease.Because transbronchial lung biopsy failed to establish a histologic diagnosis, right middle lobectomy was undertaken by video-assisted thoracoscopic surgery. The gross surgical specimen harbored a single and sizeable (8.0 × 4.0 cm) cystic lesion containing multiple yellow-white nodules. A diagnosis of mesenchymal cystic and chondroid hamartoma was ultimately rendered. This particular case is noteworthy, given the initial clinical resemblance to primary lung cancer.

Association between Sleep Duration and Metabolic Disorders among Filipino Immigrant Women: The Filipino Women's Diet and Health Study (FiLWHEL).

Background: Sleep plays a complex role in metabolic regulation, and the underlying linkage has not been clearly defined. We investigated the association between sleep duration and metabolic disorders in Filipino immigrants in Korea. Methods: We analyzed 410 participants from the 2014 to 2016 baseline population of the Filipino Women's Diet and Health Study. Usual sleep duration was self-reported, and anthropometric parameters were measured directly. Blood glucose, lipid, and insulin levels were examined from fasting serum samples. We used general linear models to acquire least squares (LS) means and logistic regression models to calculate odds ratios to test the cross-sectional association between sleep duration and metabolic markers with 95% confidence intervals (CIs). Results: We found a statistically significant linear association between increased sleep duration and elevated triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C). LS means (95% CI) of <5, 5-6, 7-8, and >8 hours of sleep were 81.74 (71.43 to 93.54), 85.15 (76.65 to 94.59), 86.33 (77.84 to 95.75), and 105.22 (88.07 to 125.71), respectively, for triglycerides (P trend=0.049) and 174.52 (165.02 to 184.57), 180.50 (172.79 to 188.55), 182.51 (174.83 to 190.53), and 190.16 (176.61 to 204.74), respectively, for total cholesterol (P trend= 0.042). For LDL-C, the LS means (95% CI) were 97.34 (88.80 to 106.71), 100.69 (93.73 to 108.18), 104.47 (97.35 to 112.10), and 109.43 (96.94 to 123.54), respectively (P trend=0.047). Statistical significance persisted after additional adjustment for body mass index. The association with triglycerides was limited to current alcohol drinkers (P interaction=0.048). Conclusion: Longer sleep duration was associated with increased triglyceride, total cholesterol, and LDL-C levels. The association with triglycerides was more pronounced among moderate alcohol drinkers.

Dopaminergic cell protection and alleviation of neuropsychiatric disease symptoms by VMAT2 expression through the class I HDAC inhibitor TC-H 106.

The importance of vesicular monoamine transporter 2 (VMAT2) in dopamine regulation, which is considered crucial for neuropsychiatric disorders, is currently being studied. Moreover, the development of disease treatments using histone deacetylase (HDAC) inhibitors (HDACi) is actively progressing in various fields. Recently, research on the possibility of regulating neuropsychiatric disorders has been conducted. In this study, we evaluated whether VMAT2 expression increased by an HDACi can fine-tune neuropsychotic behavior, such as attention deficit hyperactivity disorder (ADHD) and protect against the cell toxicity through oxidized dopamine. First, approximately 300 candidate HDACi compounds were added to the SH-SY5Y dopaminergic cell line to identify the possible changes in the VMAT2 expression levels, which were measured using quantitative polymerase chain reaction. The results demonstrated, that treatment with pimelic diphenylamide 106 (TC-H 106), a class I HDACi, increased VMAT2 expression in both the SH-SY5Y cells and mouse brain. The increased VMAT2 expression induced by TC-H 106 alleviated the cytotoxicity attributed to 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenylpyridinium (MPP+ ) and free dopamine treatment. Moreover, dopamine concentrations, both intracellularly and in the synaptosomes, were significantly elevated by increased VMAT2 expression. These results suggest that dopamine concentration regulation by VMAT2 expression induced by TC-H 106 could alter several related behavioral aspects that was confirmed by attenuation of hyperactivity and impulsivity, which were major characteristics of animal model showing ADHD-like behaviors. These results indicate that HDACi-increased VMAT2 expression offers sufficient protections against dopaminergic cell death induced by oxidative stress. Thus, the epigenetic approach could be considered as therapeutic candidate for neuropsychiatric disease regulation.

Left anterior descending artery dissection with retrograde aortic dissection during percutaneous coronary intervention: a case report.

Retrograde catheter-induced coronary artery dissection during percutaneous coronary intervention is an exceedingly rare occurrence, and the likelihood of it extending into the aorta is even more uncommon. Typically, surgical treatment involves aortic root replacement combined with coronary artery bypass grafting. However, in this particular case, a meticulous approach was employed. By carefully guiding wires into the true lumens and placing stents in the proximal left main and left anterior descending arteries, the immediate complications were averted by obstructing the retrograde flow in the false lumen. Subsequently, an off-pump coronary artery bypass was performed using the left internal mammary artery to the left anterior descending artery, without the need to manipulate the aorta. This approach resulted in a short operation time and the absence of any other complications.

Dietary intakes of branched-chain amino acids and plasma lipid profiles among filipino women in Korea: the Filipino Women's Diet and Health Study (FiLWHEL).

BACKGROUND: The potential role of dietary branched-chain amino acids (BCAA) in metabolic health, including cardiovascular disease and diabetes, is evolving, and it is yet to be understood if dietary BCAA intakes are associated with plasma lipid profiles or dyslipidaemia. This study tested the association of dietary BCAA intakes with plasma lipid profiles and dyslipidaemia among Filipino women in Korea. METHODS: Energy-adjusted dietary BCAA intakes (isoleucine, leucine, valine, and total BCAA) and fasting blood profiles of triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) were determined in a sample of 423 women enrolled in the Filipino Women's Diet and Health Study (FiLWHEL). The generalized linear model was applied to estimate least-square (LS) means and 95% confidence intervals (CIs) and compare plasma TG, TC, HDL-C, and LDL-C across tertile distribution of energy-adjusted dietary BCAA intakes at P < 0.05. RESULTS: Mean of energy-adjusted dietary total BCAA intake was 8.3 ± 3.9 g/d. Average plasma lipid profiles were 88.5 ± 47.4 mg/dl for TG, 179.7 ± 34.5 mg/dl for TC, 58.0 ± 13.7 mg/dl for HDL-C, and 104.0 ± 30.5 mg/dl for LDL-C. LS means, and 95% CIs across tertiles of energy-adjusted total BCAA intakes were 89.9 mg/dl, 88.8 mg/dl and 85.8 mg/dl (P-trend = 0.45) for TG, 179.1 mg/dl, 183.6 mg/dl and 176.5 mg/dl (P-trend = 0.48) for TC, 57.5 mg/dl, 59.6 mg/dl and 57.1 mg/dl (P-trend = 0.75) for HDL-C and 103.6 mg/dl, 106.2 mg/dl and 102.3 mg/dl (P-trend = 0.68) for LDL-C. Furthermore, the multivariable-adjusted prevalence ratios and 95% confidence intervals for dyslipidaemia across increasing tertile distribution of energy-adjusted total BCAA intake were; 1.00, 0.67 (0.40, 1.13) and 0.45 (0.16, 1.27; P-trend = 0.03) for the first, second and third tertile, respectively. CONCLUSIONS: Higher dietary intakes of BCAA presented a statistically significant inverse trend with the prevalence of dyslipidaemia among Filipino women in this study and testing these associations in longitudinal studies may be necessary to confirm these findings.

Associations of Dietary Intakes of Total and Specific Types of Fat with Blood Lipid Levels in the Filipino Women's Diet and Health Study (FiLWHEL).

Background: Limited evidence exists on the association between dietary fat intake and lipid profiles in Southeast Asian populations. Objectives: We aimed to examine the cross-sectional associations of dietary intake of total and specific types of fat with dyslipidemia in Filipino immigrant women in Korea. Methods: We included 406 Filipino women married to Korean in the Filipino Women's Diet and Health Study (FiLWHEL). Dietary fat intake was assessed using 24-hour recalls. Impaired blood lipid profiles were defined as high total cholesterol (TC) (≥200 mg/dL), high triglyceride (TG) (≥150 mg/dL), high LDL Cholesterol (LDL-C) (≥ 130 mg/dL), or low HDL cholesterol (HDL-C) (<50 mg/dL). The genomic DNA samples were genotyped using DNA chip. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. Results: Substituting carbohydrates with dietary saturated fat (SFA) intake was associated with increased prevalence of dyslipidemia; ORs (95% CIs) for subsequent tertiles compared to the first tertile were 2.28 (1.19-4.35), and 2.88 (1.29-6.39) (P for trend = 0.02). When we examined individual markers, ORs (95% CIs, P for trend) comparing the third to the first tertile were 3.62 (1.53-8.55, 0.01) for high TC, 1.46 (0.42-5.10, 0.72) for high TG, 4.00 (1.48-10.79, 0.02) for high LDL-C, and 0.69 (0.30-1.59, 0.36) for low HDL-C. When we examined the interaction by LDL-C-related polymorphisms, the association with dyslipidemia was more pronounced among participants with CC alleles than among those with T alleles of rs6102059 (P for interaction = 0.01). Conclusions: High dietary SFA intake was significantly associated with a high prevalence of dyslipidemia in Filipino women in Korea. Further prospective cohort studies are warranted to determine risk factors for CVD in Southeast Asian populations.

Applicability of oil adsorption pads based on properties of very-low sulfur fuel oil: Implications for oil spill remediation in a marine environment.

Given the urgent need for continuous and diverse research on marine fuel oils, this study investigated the effects of the properties of fuel oil on its adsorption to adsorbent materials. Very low-sulfur fuel oil (VLSFO), which is increasingly being utilized in vessels, was tested to simulate adsorption from seawater at temperatures of 1, 15, and 25 °C. Temperature minimally affected the adsorbed amount of low-viscosity VLSFOs and high-sulfur fuel oils. Conversely, the amount of high-viscosity VLSFO adsorbed decreased sharply at 1 and 15 °C. The viscosity, pour point, aromatics, asphaltenes, and wax contents of fuel oils determined the amounts adsorbed on an adsorbent. Therefore, at low sea surface temperatures associated with VLSFO spills, adsorption may be challenging. These findings highlight the need to improve fuel oil quality to accommodate spills in the marine environment.

Comparison of cardiovascular disease risk factors among FiLWHEL (2014-2016), NNS (2013) and KNHANES (2013-2015) women.

OBJECTIVES: This study assessed the CVD risk factors among Filipino women (FW) in Korea and compared them with FW in the Philippines and women in Korea (KW). METHODS: A cohort of 504 women from the Filipino Women's Health and Diet Study (FiLWHEL) aged 20-57 years old were age-matched (1:1 ratio) with women from the 2013 National Nutrition Survey in the Philippines and the 2013-2015 Korean National Health and Nutrition Examination Survey. Anthropometric data, blood pressure (BP), lipid and glucose levels were compared across the four populations by calculating the odds ratio (OR)s and 95% confidence interval (CI)s using conditional logistic regression models. RESULTS: Compared to KW, FW in Korea and FW in the Philippines were more than 2 and 3 times higher odds of having obesity for BMI ≥ 30 kg/m2 and waist circumference ≥ 88 cm, respectively. However, FW in Korea had the highest odds (OR 5.51, 95% CI 3.18-9.56) of having hypertension compared to KW. FW in the Philippines had the highest odds of having dyslipidemia (compared to KW, total cholesterol ≥ 200 mg/dL: OR 8.83, 95% CI 5.30-14.71; LDL-C ≥ 130 mg/dL: OR 3.25, 95% CI 2.13-4.98; and triglyceride ≥ 150 mg/dL: OR 2.59, 95% CI 1.59-4.22), but FW in Korea and KW had similar prevalence of dyslipidemia. CONCLUSIONS: FW in Korea had higher prevalence of obesity and hypertension, with similar prevalence of dyslipidemia compared to KW in this sample. FW in the Philippines had higher prevalence of dyslipidemia compared to FW in Korea. Further prospective studies are warranted to examine the CVD risk factors among continental and native-born Filipino women.

An ensemble method based on marginal-effect models (EMM) for estimating usual food intake from single-day dietary data and internal/external two-day dietary data.

BACKGROUND: With collection of repeated 24-hour recalls, there exist challenges in usual intake estimation, including infeasibility of multiple dietary assessments, and shortage of non-zero intakes for episodically consumed foods. OBJECTIVES: We developed an ensemble method based on marginal-effect models (EMM), which estimates usual intake distribution using single-day data with internal or external two-day data. METHODS: The performance of the EMM was evaluated and compared with the National Cancer Institute (NCI) method and NCI 1-d method, via simulations with various scenarios and real data analyses of red meat, fish, and protein from Korea National Health and Nutrition Examination Survey (KNHANES). RESULTS: Simulations indicated the EMM (maximum bias of 1.67, 3.17, 8.57, 11.63 for average, median, 75%-tile, 95%-tile, respectively) provided more accurate estimation than the NCI method (maximum bias of 4.18, 9.43, 7.56, 37.43) across various scenarios on intake probability and within-person variation. The EMM showed robust estimation when an insufficient number of people have positive consumption on two days. In simulations with various external variance ratios, the EMM showed similar or superior performance to the NCI 1-d method. The EMM produced more stable estimates of usual intake distributions for red meat, fish, and protein than the two NCI methods. CONCLUSION: The proposed EMM showed substantial improvement over the NCI methods when data contain a relatively small number of people with positive consumption on two days; is robust when food intake probability is very low or high; and estimates an external variance ratio with relatively low bias.

Multiple cranial nerve palsies with small angle exotropia following COVID-19 mRNA vaccination in an adolescent: A case report.

BACKGROUND: Several vaccines against the severe acute respiratory syndrome coronavirus 2 have been approved and widely distributed, raising public concerns regarding the side effects of immunization, as the incidence of ease. Although many adverse events following the coronavirus disease 2019 (COVID-19) vaccine have been reported, neurological complications are relatively uncommon. Herein, we report a rare case of multiple cranial palsies following COVID-19 vaccination in an adolescent patient. CASE SUMMARY: A previously healthy, 14-year-old Asian girl with facial palsy presented to the emergency department with inability to close the right eye or wrinkle right side of the forehead, and pain in the right cheek. She had received second dose of the COVID-19 mRNA vaccine (Pfizer-BioNTech) 18 days before onset of symptoms. She was diagnosed with Bell's palsy and prescribed a steroid (1 mg/kg/day methylprednisolone) based on symptoms and magnetic resonance imaging findings. However, the next day, all sense of taste was lost with inability to swallow solid food; the gag reflex was absent. Horizontal diplopia was also present. Due to worsening of her condition, she was given high-dose steroids (1 g/day methylprednisolone) for 3 days and then discharged with oral steroids. Improvement in the symptoms was noted 4 days post steroid treatment completion. At the most recent follow-up, her general condition was good with no symptoms except diplopia; ocular motility disturbances were noted. Hence, prism glasses were prescribed for diplopia relief. CONCLUSION: Small-angle exotropia was observed in the facial, trigeminal, and glossopharyngeal nerve palsies, in our patient. The etiology of this adverse effect following vaccination was thought to be immunological.

Establishment of a platform for measuring mitochondrial oxygen consumption rate for cardiac mitochondrial toxicity.

The heart has an abundance of mitochondria since cardiac muscles require copious amounts of energy for providing continuous blood through the circulatory system, thereby implying that myocardial function is largely reliant on mitochondrial energy. Thus, cardiomyocytes are susceptible to mitochondrial dysfunction and are likely targets of mitochondrial toxic drugs. Various methods have been developed to evaluate mitochondrial toxicity by evaluating toxicological mechanisms, but an optimized and standardized assay for cardiomyocytes remains unmet. We have therefore attempted to standardize the evaluation system for determining cardiac mitochondrial toxicity, using AC16 human and H9C2 rat cardiomyocytes. Three clinically administered drugs (acetaminophen, amiodarone, and valproic acid) and two anticancer drugs (doxorubicin and tamoxifen) which are reported to have mitochondrial effects, were applied in this study. The oxygen consumption rate (OCR), which directly reflects mitochondrial function, and changes in mRNA levels of mitochondrial respiratory complex I to complex V, were analyzed. Our results reveal that exposure to all five drugs results in a concentration-dependent decrease in the basal and maximal levels of OCR in AC16 cells and H9C2 cells. In particular, marked reduction in the OCR was observed after treatment with doxorubicin. The reduction in OCR after exposure to mitochondrial toxic drugs was found to be associated with reduced mRNA expression in the mitochondrial respiratory complexes, suggesting that the cardiac mitochondrial toxicity of drugs is majorly due to dysfunction of mitochondrial respiration. Based on the results of this study, we established and standardized a protocol to measure OCR in cardiomyocytes. We expect that this standardized evaluation system for mitochondrial toxicity can be applied as basic data for establishing a screening platform to evaluate cardiac mitochondrial toxicity of drugs, during the developmental stage of new drug discovery.

MicroRNA-769-3p Acts as a Prognostic Factor in Oral Squamous Cell Cancer by Modulating Stromal Genes.

miR-769-3p expression is suppressed in the stromal subtype of head and neck squamous cell carcinoma (HNSCC); however, its role in stromal HNSCC has not been fully elucidated. To investigate the biological relevance of miR-769-3p in the stromal phenotype, we established oral squamous cell cancer (OSCC) cell lines, namely CAL27, HSC3, and YD8, overexpressing miR-769-3p. miR-769-3p expression was positively and negatively correlated with interferon-gamma-related genes and MYC target gene sets, respectively. miR-769-3p decreased OSCC cell migration and invasion as well as mesenchymal marker expression and increased epithelial marker expression. Moreover, miR-769-3p enhanced OSCC cell sensitivity to 5-fluorouracil. High miR-769-3p expression was associated with good prognosis of HNSCC patients. Collectively, these results suggest that miR-769-3p suppression enhances stromal gene expression and promotes the epithelial-to-mesenchymal transition. Therefore, miR-769-3p may be a potential biomarker of the miRNA phenotype in OSCC patients.

Echinochrome A Inhibits Melanogenesis in B16F10 Cells by Downregulating CREB Signaling.

Excessive increase in melanin pigment in the skin can be caused by a variety of environmental factors, including UV radiation, and can result in spots, freckles, and skin cancer. Therefore, it is important to develop functional whitening cosmetic reagents that regulate melanogenesis. In this study, we investigated the effects of echinochrome A (Ech A) on melanogenesis in the B16F10 murine melanoma cell line. We triggered B16F10 cells using α-MSH under Ech A treatment to observe melanin synthesis and analyze expression changes in melanogenesis-related enzymes (tyrosinase, tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2)) at the mRNA and protein levels. Furthermore, we measured expression changes in the microphthalmia-associated transcription factor (MITF), CREB, and pCREB proteins. Melanin synthesis in the cells stimulated by α-MSH was significantly reduced by Ech A. The expression of the tyrosinase, TYRP1, and TYRP2 mRNA and proteins was significantly decreased by Ech A, as was that of the MITF, CREB, and pCREB proteins. These results show that Ech A suppresses melanin synthesis by regulating melanogenesis-related enzymes through the CREB signaling pathway and suggest the potential of Ech A as a functional agent to prevent pigmentation and promote skin whitening.

A Comparison of Clinical Features of Youth with and without Rhinitis Signs and Symptoms Who Are Hospitalized for Headache.

Headache and allergic rhinitis (AR) are common in children and often co-occur. We investigated the clinical characteristics of pediatric headaches and the association of AR and chronic headaches. We retrospectively reviewed the medical records of patients admitted to our pediatric inpatient and outpatient clinics with complaints of headache between January 2017 and June 2020 for headache-specific history, AR signs and symptoms, allergy skin prick test, inhalant multiple allergen simultaneous test results, laboratory and imaging findings, and medication history. The patients were divided into three subgroups: AR, non-AR, and headache groups, reporting 45.7% patients with headache alone, 13.7% with additional AR, and 31.6% with abnormal imaging findings, suggesting that headache was combined with sinusitis (24.3%) or mastoiditis (7.3%). Furthermore, 6% of the patients had both AR and sinusitis. Body mass index (BMI) differed significantly between the AR and the non-AR and headache groups (p = 0.03). The BMI differed significantly according to headache severity (p ˂ 0.001). The most common allergen was "dust or mites" (41.1%). Acetaminophen (35.9%) was the most commonly used painkiller. The coexistence of AR and headache may indicate that these conditions share a similar pathophysiology. Better management of allergies may facilitate diagnosis, treatment, and prophylaxis of headaches.