Synthetic Strategies toward Ortho-3-propanoate Substituted Aryl Phosphonates by Three-Component Coupling Reactions of Arynes, Phosphites, and Acrylates.

Mild, metal-free, and operationally simple three-component coupling reactions involving arynes, phosphites, and acrylates have been achieved. The reaction proceeded well with α- or ß-substituted acrylates. Additionally, various functional groups were tolerated under these reaction conditions, resulting in diverse ortho-3-propanoate-substituted aryl phosphonates. Moreover, the reaction can be used to synthesize a range of organophosphorus compounds present in natural products, materials, and biologically active compounds.

Identification of Short-Chain Fatty Acids for Predicting Preterm Birth in Cervicovaginal Fluid Using Mass Spectrometry.

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, predicting and preventing PTB are important. In this study, we investigated the potential of using short-chain fatty acid (SCFA) levels, specific vaginal microbiota-derived metabolites, as a biomarker in predicting PTB using gas chromatography/mass spectrometry. Cervicovaginal fluid (CVF) was collected from 89 pregnant women (29 cases of PTB vs. 60 controls) without evidence of other clinical infections, and SCFA levels were measured. Furthermore, the PTB group was divided into two subgroups based on birth timing after CVF sampling: delivery ≤ 2 days after sampling (n = 10) and ≥2 days after sampling (n = 19). The concentrations of propionic acid, isobutyric acid, butyric acid, valeric acid, hexanoic acid, and heptanoic acid were significantly higher in the PTB group than in the term birth (TB) group (p < 0.05). In particular, the concentrations of propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid were continuously higher in the PTB group than in the TB group (p < 0.05). In the delivery ≤ 2 days after sampling group, the propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid levels were significantly higher than those in the other groups (p < 0.05). This study demonstrated a significant association between specific SCFAs and PTB. We propose these SCFAs as potential biomarkers for the prediction of PTB.

Assessment of oral hypofunction and its association with age among Korean community-dwelling older adults.

BACKGROUND: Due to the increasing proportion of older adults in Korea and growing interest in aging, the concepts of oral aging and oral hypofunction have recently been introduced. Thus, it is necessary to investigate the age-specific oral function levels of Korean older adults and develop expert intervention methods for healthy aging. METHODS: Dysphagia, independence of daily living, and oral hypofunction were assessed in 206 older adults living in Wonju, Gangwon State, South Korea. Subjective dysphagia was assessed through self-report questionnaires using the Dysphagia Handicap Index (DHI), the Korean version of Eating Assessment Tool-10, and the Korean version of the Modified Barthel Index. In addition, the oral hypofunction assessment items included decreased chewing ability, occlusal pressure, tongue pressure, oral dryness, and oral cleanliness. RESULTS: DHI increased significantly with age, with those in their 80 s reporting the most difficulty swallowing. Oral function in terms of chewing ability (maximum occlusal pressure and number of remaining teeth), maximum occlusal pressure, and maximum tongue pressure also declined with increasing age. While there was no significant difference in oral dryness by age, those in their 80 s had dry mouth according to the criteria of the oral moisture checking device. CONCLUSIONS: In an assessment of oral function in community-dwelling, independent Korean older adults, the number of items that were assessed as oral hypofunction increased with age. The findings can be used to standardize the oral hypofunction assessment item and develop age-based individualized intervention plans for the early management of oral health and individual oral myofunctional rehabilitation in Korean community-dwelling older adults.

Human platelet mitochondria improve the mitochondrial and cardiac function of donor heart.

Mitochondria transplantation emerges as an effective therapeutic strategy for ischemic-related diseases but the roles in the donor hearts for transplant remain unidentified. Here, we investigated whether the preservation of the donor heart with human platelet-derived mitochondria (pl-MT) could improve mitochondrial and cardiac function. Incubation with pl-MT resulted in the internalization of pl-MT and the enhancement of ATP production in primary cardiomyocytes. In addition, incubation of rat hearts with pl-MT ex vivo for 9 h clearly demonstrated pl-MT transfusion into the myocardium. Mitochondria isolated from the hearts incubated with pl-MT showed increased mitochondrial membrane potential and greater ATP synthase activity and citrate synthase activity. Importantly, the production of reactive oxygen species from cardiac mitochondria was not different with and without pl-MT incubation. Functionally, the heartbeat and the volume of coronary circulation perfusate were significantly increased in the Langendorff perfusion system and the viability of cardiomyocytes was increased from pl-MT hearts.Taken together, these results suggest that incubation with Pl-MT improves mitochondrial activity and maintains the cardiac function of rat hearts with prolonged preservation time. The study provides the proof of principle for pl-MT application as an enhancer of the donor heart.

PM2.5 concentrations of outdoor tobacco smoke at different distances from the smoking source: Is there an optimal distance for a designated smoking area?

INTRODUCTION: Many countries have enacted indoor smoke-free policies, and some have established outdoor non-smoking areas. However, no clear standard for determining the optimal distance for these outdoor non-smoking zones remains. This study aimed to evaluate outdoor tobacco smoke (OTS) exposure up to a distance of 21 m and to identify factors influencing OTS levels. METHODS: To assess OTS levels, PM2.5 concentrations were measured at distances of 6, 12, 15, 18, and 21 m using real-time aerosol monitors. Between August and October 2022, a total of 164 measurements were undertaken. The background PM2.5 concentration was gauged for 5 minutes before smoking commenced and then re-measured 3 minutes during smoking. OTS levels were determined by calculating the difference between the average background PM2.5 and the average PM2.5 concentrations during smoking. A one-sample t-test was employed to ascertain if the OTS levels at each distance were significantly elevated compared to 0 µg/m3. Furthermore, a multiple linear regression analysis was conducted to determine the factors influencing OTS levels. RESULTS: The mean OTS levels recorded at all specified distances significantly surpassed 0 µg/m3. The regression analysis revealed that the OTS levels correlated significantly with distance and wind speed. Specifically, OTS levels diminished as distance expanded and wind speed reduced. CONCLUSIONS: OTS levels, even at 21 m, were significantly greater than 0 µg/m3. Our results provide robust evidence supporting the establishment of outdoor non-smoking zone up to 21 m. IMPLICATIONS: Outdoor tobacco smoke (OTS) level was determined by PM2.5 concentration. The OTS levels significantly exceeded 0 µg/m3 at every measured distance up to 21 m. In the regression model, OTS levels notably correlated with distance and wind speed. OTS levels diminished as distance expanded and wind speed reduced.

Can cartilage intermediate layer protein 1 (CILP1) use as a novel biomarker for canine myxomatous mitral valve degeneration levels or not?

BACKGROUND: Myxomatous mitral valve degeneration (MMVD) is the most common degenerative heart disease in dogs and is associated with irreversible changes in the valve tissue. Although traditional cardiac biomarkers are efficient for diagnosing MMVD, there are limitations, therefore, it is important to find novel biomarkers. Cartilage intermediate layer protein 1 (CILP1), an extracellular matrix-derived protein, acts as a transforming growth factor-ß antagonist and is involved in myocardial fibrosis. This study aimed to evaluate serum CILP1 levels in canines with MMVD. Dogs with MMVD were staged according to the American College of Veterinary Internal Medicine consensus guidelines. Data analysis was performed using the Mann-Whitney U test, Spearman's correlation, and receiver operating characteristic (ROC) curves. RESULTS: CILP1 levels were elevated in dogs with MMVD (n = 27) compared to healthy controls (n = 8). Furthermore, results showed that CILP1 levels were significantly higher in stage C group dogs compared to healthy controls. The ROC curve of CILP1 and NT-proBNP were good predictors of MMVD, although no similarity was observed between the two. Left ventricular end-diastolic diameter normalized to the body weight (LVIDdn) and left atrial to aorta dimension (LA/Ao) showed a strong association with CILP1 levels; however, no correlation was observed between CILP1 levels and vertebral heart size (VHS) and vertebral left atrial score (VLAS). The optimal cut-off value was selected from the ROC curve and dogs were classified according to the cut-off value (1.068 ng/mL, sensitivity 51.9%, specificity 100%). Results showed a significant association of CILP1 with cardiac remodeling indicators, such as VHS, VLAS, LA/Ao, and LVIDdn. CONCLUSIONS: CILP1 can be an indicator of cardiac remodeling in canines with MMVD and therefore, can be used as an MMVD biomarker.

Differences in Korean adult inpatients' oral care behaviour in daily life and hospitals.

OBJECTIVES: The objectives of the study were to identify the differences in oral care methods between current and past hospitalizations and to investigate the need for inpatient oral care education for South Korean adults who have been hospitalized for more than 24 h. METHODS: This study employed a cross-sectional design. Between 23 December 2019 and 4 May 2020, a questionnaire was administered to 200 adult inpatients awaiting treatment and their guardians at university hospitals or clinics. Of these, the data of 195 patients were analysed. Frequency analysis, descriptive statistics and chi-square tests were used for data analysis. RESULTS: In daily life, the participants reported brushing their teeth thrice a day (52.3%) for 2 min (60%). A single product was the most used (51.3%). During hospitalization, 40% of the participants brushed their teeth thrice or more a day, 84.1% brushed for <1 min, and 83.6% did not use additional oral care products. CONCLUSIONS: Differences were observed between South Korean adults' oral care behaviours in daily life and those performed in hospitals. Oral hygiene habits, the frequency and duration of tooth brushing, and the use of oral care products decreased during hospitalization. Our findings can be applied to the development of oral care interventions for inpatients, while considering changes in the hospitalization environment and physical activity levels during hospitalization.

Visible-Light-Induced Organophotocatalytic Difunctionallization: Open-Air Hydroxysulfurization of Aryl Alkenes with Aryl Thiols.

Herein, we report a regioselective visible-light-induced organophotoredox catalytic difunctionalization method to prepare ß-hydroxysulfides using aryl alkenes and aryl thiols as substrates. The reaction provides a wide substrate scope of aryl alkenes (from simple styrene to complex bioactive compounds) and aryl thiols (from diverse heteroaromatic thiols to nonheteroaromatic thiols) (total 45 examples, up to 88% yield). Based on the combined experimental and computational studies, we demonstrate that in situ generated hydroperoxyl radicals from O2 in air react with benzylic radicals, which restrains the reaction between benzylic radicals and the acidic form of thiols in a classical thiol-ene radical reaction. We show that difunctionalization is possible due to the choice of bases, diluted substrate concentrations, increment in catalyst loading, and selection of suitable aryl thiols under aerobic conditions. Considering the biological importance of heteroaromatic thiols and the lack of methods to install them, our approach offers a platform to derive various ß-hydroxysulfides that contain aromatic elements.

Platelet-derived mitochondria transfer facilitates wound-closure by modulating ROS levels in dermal fibroblasts.

Platelets are known to improve the wound-repair capacity of mesenchymal stem cells (MSCs) by transferring mitochondria intercellularly. This study aimed to investigate whether direct transfer of mitochondria (pl-MT) isolated from platelets could enhance wound healing in vitro using a cell-based model. Wound repairs were assessed by 2D gap closure experiment in wound scratch assay using human dermal fibroblasts (hDFs). Results demonstrated that pl-MT were successfully internalized into hDFs. It increased cell proliferation and promoted the closure of wound gap. Importantly, pl-MT suppressed both intracellular and mitochondrial ROS production induced by hydrogen peroxide, cisplatin, and TGF-ß in hDFs. Taken together, these results suggest that pl-MT transfer might be used as a potential therapeutic strategy for wound repair.

What is the context? During the wound healing process, abnormal regulation of ROS and inflammation delays the healing process, resulting in chronic non-healing wounds.Mitochondria are key organelles responsible for the ROS generation. Mitochondrial dysfunction has been implicated in delayed wound repair.Mitochondria transfer, which utilizes intact mitochondria isolated from healthy cells to recover from disease, has been applied in various clinical studies, but additional evidence is needed to apply it to wound healing.What is new? In this study, we chose platelets as a cell source for mitochondrial transfer. We isolated the functional mitochondria from platelets and applied them to wound healing.What is the impact? This study provides evidence that platelet-derived mitochondria (pl-MT) improve the wound healing progress by increasing the viability of dermal fibroblasts and suppressing intracellular and mitochondrial ROS production.Platelets have also been demonstrated to be a suitable cell source for mitochondrial transfer.

Particulate matter-induced atmospheric skin aging is aggravated by UVA and inhibited by a topical l-ascorbic acid compound.

Ambient particulate matter (PM) is a major contributor to environmental air pollution-associated skin damage. However, most published studies are observational or epidemiologic and have not mechanistically investigated the effects of air pollutants on cellular senescence and aging, particularly in combination with ultraviolet (UV) radiation. Herein, we analyzed whether UVA aggravates the PM-induced inflammatory cascade, which contributes to the aging of skin-derived cells. We hypothesized that cellular senescence is involved in PM&UVA-induced aging and tested whether an l-ascorbic acid compound (LAC), containing vitamin E and ferulic acid, can inhibit PM&UVA-induced aging. PM&UVA-exposed HDFs showed further elevated reactive oxygen species (ROS) levels detected by flow cytometry. We then demonstrated that PM induces MAPK signaling activation and the expression of AhR and NF-κB, responses that are both exacerbated by UVA. The levels of inflammatory cytokines, IL-1ß and IL-6, were significantly higher in the PM&UVA-exposed group which resulted in increased transcription of MMPs, causing downregulation of type I collagen. Meanwhile, treatment with LAC reduced the levels of ROS and inflammatory cytokines. Additionally, PM&UVA-induced SA-ß-gal production (staining assay) was reduced by LAC. These findings suggest a role of atmospheric pollution and UVA radiation in cellular senescence induction. Our findings also suggest a possible role of AhR inhibition by topical antioxidants to prevent atmospheric pollution-induced skin aging.

Bifunctional hetero di-disc for broad-spectrum influenza neutralization.

Nanodiscs containing sialic acid, which binds the hemagglutinin of the influenza virus, rupture the viral envelope and entrap viral ribonucleoproteins in the endolysosome. While nanodiscs are potent antiviral platforms, ganglioside GD1a containing α2,3-sialic acid does not cover all virus strains. When two nanodiscs containing different receptors 6'-sialyllactose and GD1a were mixed, one nanodisc inhibited the function of the other. A nanodisc loaded with two different receptors exhibited a biased activity toward only one receptor precluding the generation of a multifunctional nanodisc. Here, we suggest hetero di-disc, in which two nanodiscs loaded with each receptor were conjugated through protein trans-splicing for a broad-spectrum antiviral. The hetero di-disc showed strong antiviral activity in vitro and in vivo. Our results suggested that hetero di-discs not only expanded the inhibitory spectrum of nanodiscs but also enabled nanodisc-based delivery of multiple ligands without interference.

Preferred Migration of Mitochondria toward Cells and Tissues with Mitochondrial Damage.

Mitochondria are organelles that play a vital role in cellular survival by supplying ATP and metabolic substrates via oxidative phosphorylation and the Krebs cycle. Hence, mitochondrial dysfunction contributes to many human diseases, including metabolic syndromes, neurodegenerative diseases, cancer, and aging. Mitochondrial transfer between cells has been shown to occur naturally, and mitochondrial transplantation is beneficial for treating mitochondrial dysfunction. In this study, the migration of mitochondria was tracked in vitro and in vivo using mitochondria conjugated with green fluorescent protein (MTGFP). When MTGFP were used in a coculture model, they were selectively internalized into lung fibroblasts, and this selectivity depended on the mitochondrial functional states of the receiving fibroblasts. Compared with MTGFP injected intravenously into normal mice, MTGFP injected into bleomycin-induced idiopathic pulmonary fibrosis model mice localized more abundantly in the lung tissue, indicating that mitochondrial homing to injured tissue occurred. This study shows for the first time that exogenous mitochondria are preferentially trafficked to cells and tissues in which mitochondria are damaged, which has implications for the delivery of therapeutic agents to injured or diseased sites.

Open-Bandgap Graphene-Based Field-Effect Transistor Using Oligo(phenylene-ethynylene) Interfacial Chemistry.

Organic interfacial compounds (OICs) are required as linkers for the highly stable and efficient immobilization of bioprobes in nanobiosensors using 2D nanomaterials such as graphene. Herein, we first demonstrated the fabrication of a field-effect transistor (FET) via a microelectromechanical system process after covalent functionalization on large-scale graphene by introducing oligo(phenylene-ethynylene)amine (OPE). OPE was compared to various OICs by density functional theory simulations and was confirmed to have a higher binding energy with graphene and a lower band gap than other OICs. OPE can improve the immobilization efficiency of a bioprobe by forming a self-assembly monolayer via anion-based reaction. Using this technology, Magainin I-conjugated OGMFET (MOGMFET) showed a high sensitivity, high selectivity, with a limit of detection of 100  cfu mL-1 . These results indicate that the OPE OIC can be applied for stable and comfortable interfacing technology for biosensor fabrication.

Quantitative and Qualitative Differences of Action Verbal Fluency between Young and Older Adults.

INTRODUCTION: Action verbal fluency (AVF) task, a word fluency test, involves language and executive function and is known to be sensitive to fronto-striatal degeneration. However, the ability may also decrease qualitatively as well as quantitatively in normal aging. The objective of this study is to investigate the age-related quantitative and qualitative differences in AVF of Korean adults. METHODS: We analyzed data from 78 participants of 40 young (mean age = 28.9) and 38 older adults (mean age = 67.7). The correct responses in the AVF task were measured for quantitative analysis. Qualitatively, the mean number of arguments required by each verb was calculated for syntactic analysis. For semantic analysis, we subclassified verbs according to their characteristics (e.g., moment vs. non-moment verbs/active vs. non-active verbs) and calculated the ratio for comparison. The results of AVF were also compared to those of semantic/phonemic fluency and the Korean version of the Montreal Cognitive Assessment (MoCA-K). RESULTS: The older group showed quantitatively lower performance in AVF than the young group (p < 0.01). The result of the AVF task significantly correlated (p < 0.01) with both semantic/phonemic fluency and the MoCA-K. Also, the older group produced syntactically more simple verbs than the counterpart (p < 0.01). In the semantic analysis, the older group produced fewer moment verbs (p < 0.05) but more non-moment verbs (p < 0.05) than the young group. There was no difference in active or non-active verbs between two groups. CONCLUSION: These results indicated that the ability of AVF declines with age not only quantitatively but also qualitatively in relation to their cognitive changes.

Comparison of Serum Uric Acid in Major Depressive Disorder and Bipolar Disorder: a Retrospective Chart Review Study.

BACKGROUND: Uric acid (UA) has been suggested as a possible biomarker of bipolar disorder (BD) in recent studies. We aimed to provide a clearer comparison of UA levels between BD and major depressive disorder (MDD). METHODS: We retrospectively reviewed the medical chart records of psychiatric inpatients aged 19-60 years, whose main discharge diagnoses were either MDD or BD, with an admission between January 1, 2015 and December 31, 2018 at Seoul National University Hospital. Data such as sex, age, body mass index (BMI), medication usage, and serum UA levels were extracted. Patients with medical conditions or on medications that could influence UA levels were excluded. Age, sex, BMI, and psychiatric drug usage were considered in the comparison of serum UA between MDD and BD patients. RESULTS: Our sample consisted of 142 MDD patients and 234 BD patients. The BD patients had significantly higher serum UA levels compared to the MDD patients, without accounting for other confounding variables (5.75 ± 1.56 mg/dL vs. 5.29 ± 1.59 mg/dL, P = 0.006). T-test comparisons between psychiatric medication users and non-users revealed that mood stabilizers and antipsychotics may be relevant confounding factors in our sample analysis. The likelihood of BD diagnosis was significantly correlated with higher UA levels (odds ratio, 1.410; 95% confidence interval, 1.150-1.728; P = 0.001) when accounting for sex, age, and BMI in the logistic regression analysis. Also, accounting for mood stabilizers or antipsychotics, the likelihood of BD diagnosis was still significantly correlated with higher UA levels. CONCLUSION: Our study confirms that BD patients are significantly more likely to show higher serum UA levels than MDD patients. The high UA levels in BD point to purinergic dysfunction as an underlying mechanism that distinguishes BD from MDD. Further research is recommended to determine whether UA is a trait or a state marker and whether UA correlates with the symptoms and severity of BD.

Exposure to cigarette smoke via respiratory system may induce abnormal alterations of reproductive organs in female diabetic rats.

Cigarette smoke (CS) has harmful effects on human fertility, reproduction, and development as well as on patients suffering from metabolic diseases such as diabetes than on healthy individuals. This study was conducted to investigate the relationship between CS exposure and histological alterations of reproductive organs in female diabetic rats. We evaluated the histology of uteruses and ovaries obtained from female rats exposed to smoke from standard cigarettes for 4 weeks (28 hours a week). After CS exposure, tissue slides were made from uterine and ovarian samples and examined after hematoxylin and eosin staining. Immunohistochemistry was used for detection of matrix metallopeptidase 9 (MMP9), C-X-C chemokine receptor type 4 (CXCR4), and estrogen receptor (ER)α in the uterus and ovary. MMP9 is an inflammatory biomarker that increases during progression to endometriosis. As a chemokine receptor, CXCR4 is involved in development of the inner wall of the uterus and cell adhesion. In the uterus, the occurrence of MMP9, CXCR4, and ERα and the number of endometrial glands were increased by CS exposure, while in the ovary, occurrence of MMP9, CXCR4, ERα, proliferating cell nuclear antigen and the number of corpus lutea or cyst follicles were increased by CS exposure. Collectively, this study indicates that CS induced abnormal development of the uterus and ovary under induced diabetes, leading to adverse effects on normal function of reproductive organs in female rats. HIGHLIGHTS: Cigarette smoke (CS) exposure adversely affected reproductive organs of diabetic female rats. In the uterus, expression of matrix metallopeptidase 9 (MMP9), C-X-C chemokine receptor type 4 (CXCR4), estrogen receptor (ER)α, and the number of endometrial glands were increased by CS exposure, In the ovary, the expression of MMP9, CXCR4, ERα, and proliferating cell nuclear antigen and the number of corpus lutea or cyst follicles were increased by CS exposure. Exposure to CS via the respiratory system exerted a harmful impact on the uterus and ovary in female rats with diabetes.

Diagnostic Accuracy and Financial Implications of Age-Adjusted D-Dimer Strategies for the Diagnosis of Deep Venous Thrombosis in the Emergency Department.

BACKGROUND: Multiple D-dimer cutoffs have been suggested for older patients to improve diagnostic specificity for venous thromboembolism. These approaches are better established for pulmonary embolism. OBJECTIVES: We evaluated the diagnostic performance and compared the health system cost for previously suggested cutoffs and a new D-dimer cutoff for low-risk emergency department (ED) deep venous thrombosis (DVT) patients. METHODS: We conducted a retrospective cohort study in two large EDs involving patients aged > 50 years who had low pretest probability for DVT and had a D-dimer performed. The outcome was a diagnosis of DVT at 30 days. We evaluated the diagnostic accuracy and estimated the difference in cost for cutoffs of 500 ng/mL and the age-adjusted (age × 10) rule. A derived cutoff of 1000 ng/mL was also assessed. RESULTS: Nine hundred and seventy-two patients were included (median age 66 years; 59.5% female); 63 (6.5%) patients were diagnosed with DVT. The conventional cutoff of < 500 ng/mL demonstrated a sensitivity of 100% (95% confidence interval [CI] 94.3-100%) and a specificity of 35.6% (95% CI 32.5-38.8%). The age-adjusted approach increased specificity while maintaining high sensitivity. A new cutoff of 1000 ng/mL demonstrated improved performance: sensitivity 100% (95% CI 94.3-00%) and specificity 66.3% (95% CI 63.2-69.4%). Compared to the conventional approach, both the 1000 ng/mL cutoff and the age-adjusted cutoffs could save healthcare dollars. A cutoff of 1000 ng/mL could have saved 310 ED length of stay hours and $166,909 (Canadian dollars) in our cohort, or an average savings of 0.32 h and $172 per patient. CONCLUSIONS: Among patients aged > 50 years with suspected DVT, the age-adjusted D-dimer and a cutoff of 1000 ng/mL improved specificity without compromising sensitivity, and lowered the health care system cost compared to that for the conventional approach.

Application of outpatient cardiac testing among emergency department patients with syncope.

OBJECTIVES: 2.6% of ED syncope patients will suffer cardiac serious adverse events (SAEs) within 30 days of disposition, and outpatient cardiac testing can improve patient safety. The objective is to determine whether outpatient cardiac testing for ED syncope patients is being appropriately ordered after discharge. To this end, we describe the proportion of high-risk and non-high (low and medium)-risk ED syncope patients as per the Canadian Syncope Risk Score (CSRS) who have a SAE after ED discharge, and the proportion referred for outpatient cardiac testing. METHODS: Our multicentre prospective cohort study enrolled adult syncope patients between 2010 and 2014 in five academic EDs. We collected patient characteristics, disposition, CSRS predictors, outpatient referrals and testing results (Holter, echocardiography), and 30-day adjudicated SAE (death due to unknown/cardiac cause, myocardial infarction, arrhythmia and structural heart disease). We used descriptive statistics (mean, SD) to report our results. RESULTS: Of 3584 enrolled patients (mean age 50.9 years, 57.7% women), 800 patients (22.3%) received an outpatient referral. Of these 800 patients, 40.3% of the non-high-risk patients (305/756) and 54.5% of the high-risk patients (24/44) received outpatient cardiac testing. Of all patients who received cardiac testing, five (1.5%; 95% CI 0.6% to 3.5%) suffered outpatient SAE (60.0% arrhythmias). Of all patients who did not receive cardiac testing, four patients (0.9%; 95% CI 0.3% to 2.2%) suffered SAE (all arrhythmias). Of the 20 (45.5%) high-risk patients who did not receive testing, two patients (10.0%; 95% CI 2.8% to 30.1%) suffered arrhythmias outside the hospital, while among the 451 (59.7%) non-high-risk patients, only two (0.4%; 95% CI 0.1% to 1.6%) suffered outpatient arrhythmias. CONCLUSION: Outpatient cardiac testing is largely underused, especially among high-risk ED syncope patients. Better guidelines for outpatient cardiac testing are needed, as the practice is highly variable and mismatched with patient risk.

3,3'-Diindolylmethane Suppressed Cyprodinil-Induced Epithelial-Mesenchymal Transition and Metastatic-Related Behaviors of Human Endometrial Ishikawa Cells via an Estrogen Receptor-Dependent Pathway.

Cyprodinil (CYP) is a pyrimidine amine fungicide that has been extensively used in agricultural areas. 3,3'-Diindolylmethane (DIM) is a derivative of the dietary phytoestrogen, indole-3-carbinol (I3C), which is derived from cruciferous vegetables and considered to be a cancer-preventive phytonutrient agent. In this study, the effects of CYP and DIM were examined on the cell viability, invasion, and metastasis of human endometrial cancer cells, Ishikawa, via epithelial mesenchymal transition (EMT). CYP increased the level of cell viability of Ishikawa cells compared to DMSO as a control, as did E2. Ishikawa cells lost cell-to-cell contact and obtained a spindle-shaped or fibroblast-like morphology in response to the application of E2 or CYP by the cell morphology assay. In the cell migration and invasion assay, CYP enhanced the ability of migration and invasion of Ishikawa cells, as did E2. E2 and CYP increased the expressions of N-cadherin and Snail proteins, while decreasing the expression of E-cadherin protein as EMT-related markers. In addition, E2 and CYP increased the protein expressions of cathepsin D and MMP-9, metastasis-related markers. Conversely, CYP-induced EMT, cell migration, and invasion were reversed by fulvestrant (ICI 182,780) as an estrogen receptor (ER) antagonist, indicating that CYP exerts estrogenic activity by mediating these processes via an ER-dependent pathway. Similar to ICI 182,780, DIM significantly suppressed E2 and CYP-induced proliferation, EMT, migration, and invasion of Ishikawa cancer cells. Overall, the present study revealed that DIM has an antiestrogenic chemopreventive effect to withdraw the cancer-enhancing effect of E2 and CYP, while CYP has the capacity to enhance the metastatic potential of estrogen-responsive endometrial cancer.

Prospective validation of a clinical decision rule to identify patients presenting to the emergency department with chest pain who can safely be removed from cardiac monitoring.

BACKGROUND: Most patients with chest pain in the emergency department are assigned to cardiac monitoring for several hours, blocking access for patients in greater need. We sought to validate a previously derived decision rule for safe removal of patients from cardiac monitoring after initial evaluation in the emergency department. METHODS: We prospectively enrolled adults (age ≥ 18 yr) who presented with chest pain and were assigned to cardiac monitoring at 2 academic emergency departments over 18 months. We collected standardized baseline characteristics, findings from clinical evaluations and predictors for the Ottawa Chest Pain Cardiac Monitoring Rule: whether the patient is currently free of chest pain, and whether the electrocardiogram is normal or shows only nonspecific changes. The outcome was an arrhythmia requiring intervention in the emergency department or within 8 hours of presentation to the emergency department. We calculated diagnostic characteristics for the clinical prediction rule. RESULTS: We included 796 patients (mean age 63.8 yr, 55.8% male, 8.9% admitted to hospital). Fifteen patients (1.9%) had an arrhythmia, and the rule performed with the following characteristics: sensitivity 100% (95% confidence interval [CI] 78.2%-100%) and specificity 36.4% (95% CI 33.0%-39.6%). Application of the Ottawa Chest Pain Cardiac Monitoring Rule would have allowed 284 out of 796 patients (35.7%) to be safely removed from cardiac monitoring. INTERPRETATION: We successfully validated the decision rule for safe removal of a large subset of patients with chest pain from cardiac monitoring after initial evaluation in the emergency department. Implementation of this simple yet highly sensitive rule will allow for improved use of health care resources.