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Abstract Background Malignant peripheral nerve sheath tumor (MPNST) is an exceedingly rare and aggressive tumor, with limited literature on its management. Herein, we present our series of surgically managed craniospinal MPNSTs, analyze their outcomes, and review the literature. Methods We retrospectively reviewed surgically managed primary craniospinal MPNSTs treated at our institution between January 2005 and May 2023. Patient demographics, tumor features, and treatment outcomes were assessed. Neurological function was quantified using the Frankel grade and Karnofsky performance scores. Descriptive statistics, rank-sum tests, and Kaplan–Meier survival analyses were performed. Results Eight patients satisfied the inclusion criteria (4 male, 4 female). The median age at presentation was 38 years (range 15–67). Most tumors were localized to the spine (75%), and 3 patients had neurofibromatosis type 1. The most common presenting symptoms were paresthesia (50%) and visual changes (13%). The median tumor size was 3 cm, and most tumors were oval-shaped (50%) with well-defined borders (75%). Six tumors were high grade (75%), and gross total resection was achieved in 5 patients, with subtotal resection in the remaining 3 patients. Postoperative radiotherapy and chemotherapy were performed in 6 (75%) and 4 (50%) cases, respectively. Local recurrence occurred in 5 (63%) cases, and distant metastases occurred in 2 (25%). The median overall survival was 26.7 months. Five (63%) patients died due to recurrence. Conclusions Primary craniospinal MPNSTs are rare and have an aggressive clinical course. Early diagnosis and treatment are essential for managing these tumors. In this single-center study with a small cohort, maximal resection, low-grade pathology, young age (

Objective. Diet-related disease is rising, disproportionately affecting minority communities in which small food retail stores swamp supermarkets. Barriers to healthy food access were exacerbated by the pandemic. We examined the following: (1) individual- and household-level factors in a sample of Baltimore community members who regularly shop at corner stores and (2) how these factors are associated with indicators of dietary quality. Design. Cross-sectional data were collected using an online survey to capture sociodemographics, anthropometrics, and food sourcing, spending, and consumption patterns. Concurrent quantitative and qualitative analyses were conducted in Stata 18 and ATLAS.ti. Setting. This study was set in Baltimore, Maryland, USA. Participants. The participants included adults (n = 127) living or working in Baltimore who identified as regular customers of their neighborhood corner store. Results. The respondents were majority Black and low-income, with a high prevalence of food insecurity (62.2%) and overweight/obesity (66.9%). Most (82.76%) shopped in their neighborhood corner store weekly. One-third (33.4%) of beverage calories were attributed to sugar-sweetened beverages, and few met the recommended servings for fruits and vegetables or fiber (27.2% and 10.4%, respectively). Being Black and not owning a home were associated with lower beverage and fiber intake, and not owning a home was also associated with lower fruit and vegetable intake. Food insecurity was associated with higher beverage intake, while WIC enrollment was associated with higher fruit and vegetable and fiber intakes. Open-ended responses contextualized post-pandemic food sourcing and consumption in this setting. Conclusions. This paper helps characterize the consumers of a complex urban food system. The findings will inform future strategies for consumer-engaged improvement of local food environments.

Introduction The mastery of mechanical ventilation (MV) management is challenging, as it requires the integration of physiological and technological knowledge with critical thinking. Our aim was to create a standardized curriculum with assessment tools based on evidence-based practices to identify the skill deficit and improve knowledge in MV management.

During the COVID-19 pandemic, US schools have been encouraged to take a layered approach to prevention, incorporating multiple strategies to curb transmission of SARS-CoV-2. Using survey data representative of US public K–12 schools (N = 437), we determined prevalence estimates of COVID-19 prevention strategies early in the 2021–22 school year and describe disparities in implementing strategies by school characteristics. Prevalence of prevention strategies ranged from 9.3% (offered COVID-19 screening testing to students and staff) to 95.1% (had a school-based system to report COVID-19 outcomes). Schools with a full-time school nurse or school-based health center had significantly higher odds of implementing several strategies, including those related to COVID-19 vaccination. We identified additional disparities in prevalence of strategies by locale, school level, and poverty. Advancing school health workforce and infrastructure, ensuring schools use available COVID-19 funding effectively, and promoting efforts in schools with the lowest prevalence of infection prevention strategies are needed for pandemic preparedness.

IntroductionOn October 12, 2021, the FDA issued its first marketing granted orders for Vuse, the e-cigarette product by R.J. Reynolds Vapor Company. The public perceptions and reactions to the FDA’s Vuse authorization are prevalent on social media platforms such as Twitter/X. We aim to understand public perceptions of the FDA’s Vuse authorization in the US using Twitter/X data.MethodsThrough the Twitter/X streaming API (Application Programming Interface), 3,852 tweets between October 12, 2021, and October 23, 2021, were downloaded using the keyword of Vuse. With the elimination of retweets, irrelevant tweets, and tweets from other countries, the final dataset consisted of 523 relevant tweets from the US. Based on their attitudes toward the FDA authorization on Vuse, these tweets were coded into three major categories: positive, negative, and neutral. These tweets were further manually classified into different categories based on their contents.ResultsThere was a large peak on Twitter/X mentioning FDA’s Vuse authorization on October 13, 2021, just after the authorization was announced. Of the 523 US tweets related to FDA’s Vuse authorization, 6.12% (n=32) were positive, 26.77% (n=140) were negative, and 67.11% (n=351) were neutral. In positive tweets, the dominant subcategory was Cessation Claims (n=18, 56.25%). In negative tweets, the topics Health Risk (n=43, 30.71%), Criticize Authorization (n=42, 30.00%), and Big Tobacco (n=40, 38.57%) were the major topics. News (n=271, 77.21%) was the most prevalent topic among neutral tweets. In addition, tweets with a positive attitude tend to have more likes.DiscussionPublic perceptions and discussions on Twitter/X regarding the FDA’s Vuse authorization in the US showed that Twitter/X users were more likely to show a negative than a positive attitude with a major concern about health risks.

Context Pinus densiflora Siebold & Zucc. (Pinaceae) needle extracts ameliorate oxidative stress, but research into their anti-inflammatory effects is limited.Objective To investigate antioxidant and anti-inflammatory effects of a Pinus densiflora needles (PINE) ethanol extract in vitro and in vivo.Materials and methods We measured levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at various PINE concentrations (25, 50 and 100 μg/mL; but 6.25, 12.5 and 25 μg/mL for interleukin-1β and prostaglandin E2 (PGE2)). Thirty ICR mice were randomized to six groups: vehicle, control, PINE pre-treatment (0.1, 0.3 and 1 mg/left ear for 10 min followed by arachidonic acid treatment for 30 min) and dexamethasone. The posttreatment ear thickness and myeloperoxidase (MPO) activity were measured.Results PINE 100 μg/mL significantly decreased ROS (IC50, 70.93 μg/mL, p

BackgroundArtificial intelligence (AI) is a branch of computer science that uses advanced computational methods, such as machine learning (ML), to calculate and predict health outcomes and address patient and provider health needs. While these technologies show great promise for improving health care, especially in diabetes management, there are usability and safety concerns for both patients and providers about the use of AI/ML in health care management. ObjectiveWe aimed to support and ensure safe use of AI/ML technologies in health care; thus, the team worked to better understand (1) patient information and training needs, (2) the factors that influence patients’ perceived value and trust in AI/ML health care applications, and (3) how best to support safe and appropriate use of AI/ML-enabled devices and applications among people living with diabetes. MethodsTo understand general patient perspectives and information needs related to the use of AI/ML in health care, we conducted a series of focus groups (n=9) and interviews (n=3) with patients (n=41) and interviews with providers (n=6) in Alaska, Idaho, and Virginia. Grounded theory guided data gathering, synthesis, and analysis. Thematic content and constant comparison analysis were used to identify relevant themes and subthemes. Inductive approaches were used to link data to key concepts, including preferred patient-provider interactions and patient perceptions of trust, accuracy, value, assurances, and information transparency. ResultsKey summary themes and recommendations focused on (1) patient preferences for AI/ML-enabled device and application information, (2) patient and provider AI/ML-related device and application training needs, (3) factors contributing to patient and provider trust in AI/ML-enabled devices and applications, and (4) AI/ML-related device and application functionality and safety considerations. A number of participants (patients and providers) made recommendations to improve device functionality to guide information and labeling mandates (eg, link to online video resources and provide access to 24/7 live in-person or virtual emergency support). Other patient recommendations included (1) providing access to practice devices, (2) providing connections to local supports and reputable community resources, and (3) simplifying the display and alert limits. ConclusionsRecommendations from both patients and providers could be used by federal oversight agencies to improve utilization of AI/ML monitoring of technology use in diabetes, improving device safety and efficacy.

The Gametophytic Self-Incompatibility (GSI) system in diploid potato (Solanum tuberosum L.) poses a substantial barrier in diploid potato breeding by hindering the generation of inbred lines. One solution is gene editing to generate self-compatible diploid potatoes which will allow for the generation of elite inbred lines with fixed favorable alleles and heterotic potential. The S-RNase and HT genes have been shown previously to contribute to GSI in the Solanaceae family and self-compatible S. tuberosum lines have been generated by knocking out S-RNase gene with CRISPR-Cas9 gene editing. This study employed CRISPR-Cas9 to knockout HT-B either individually or in concert with S-RNase in the diploid self-incompatible S. tuberosum clone DRH-195. Using mature seed formation from self-pollinated fruit as the defining characteristic of self-compatibility, HT-B-only knockouts produced little or no seed. In contrast, double knockout lines of HT-B and S-RNase displayed levels of seed production that were up to three times higher than observed in the S-RNase-only knockout, indicating a synergistic effect between HT-B and S-RNase in self-compatibility in diploid potato. This contrasts with compatible cross-pollinations, where S-RNase and HT-B did not have a significant effect on seed set. Contradictory to the traditional GSI model, self-incompatible lines displayed pollen tube growth reaching the ovary, yet ovules failed to develop into seeds indicating a potential late-acting self-incompatibility in DRH-195. Germplasm generated from this study will serve as a valuable resource for diploid potato breeding.

Abstract Background Research capacity building (RCB) initiatives have gained steady momentum in health settings across the globe to reduce the gap between research evidence and health practice and policy. RCB strategies are typically multidimensional, comprising several initiatives targeted at different levels within health organisations. Research education and training is a mainstay strategy targeted at the individual level and yet, the evidence for research education in health settings is unclear. This review scopes the literature on research education programs for nurses and allied health professionals, delivered and evaluated in healthcare settings in high-income countries. Methods The review was conducted systematically in accordance with the Joanna Briggs Institute scoping review methodology. Eleven academic databases and numerous grey literature platforms were searched. Data were extracted from the included full texts in accordance with the aims of the scoping review. A narrative approach was used to synthesise findings. Program characteristics, approaches to program evaluation and the outcomes reported were extracted and summarised. Results Database searches for peer-reviewed and grey literature yielded 12,457 unique records. Following abstract and title screening, 207 full texts were reviewed. Of these, 60 records were included. Nine additional records were identified on forward and backward citation searching for the included records, resulting in a total of 69 papers describing 68 research education programs. Research education programs were implemented in fourteen different high-income countries over five decades. Programs were multifaceted, often encompassed experiential learning, with half including a mentoring component. Outcome measures largely reflected lower levels of Barr and colleagues’ modified Kirkpatrick educational outcomes typology (e.g., satisfaction, improved research knowledge and confidence), with few evaluated objectively using traditional research milestones (e.g., protocol completion, manuscript preparation, poster, conference presentation). Few programs were evaluated using organisational and practice outcomes. Overall, evaluation methods were poorly described. Conclusion Research education remains a key strategy to build research capacity for nurses and allied health professionals working in healthcare settings. Evaluation of research education programs needs to be rigorous and, although targeted at the individual, must consider longer-term and broader organisation-level outcomes and impacts. Examining this is critical to improving clinician-led health research and the translation of research into clinical practice.

Background and Purpose The Save ChildS Study demonstrated that endovascular thrombectomy (EVT) is a safe treatment option for pediatric stroke patients with large vessel occlusions (LVOs) with high recanalization rates. Our aim was to determine the long-term cost, health consequences and cost-effectiveness of EVT in this patient population. Methods In this retrospective study, a decision-analytic Markov model estimated lifetime costs and quality-adjusted life years (QALYs). Early outcome parameters were based on the entire Save ChildS Study to model the EVT group. As no randomized data exist, the Save ChildS patient subgroup with unsuccessful recanalization was used to model the standard of care group. For modeling of lifetime estimates, pediatric and adult input parameters were obtained from the current literature. The analysis was conducted in a United States setting applying healthcare and societal perspectives. Probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set to $100,000 per QALY. Results The model results yielded EVT as the dominant (cost-effective as well as cost-saving) strategy for pediatric stroke patients. The incremental effectiveness for the average age of 11.3 years at first stroke in the Save ChildS Study was determined as an additional 4.02 lifetime QALYs, with lifetime cost-savings that amounted to $169,982 from a healthcare perspective and $254,110 when applying a societal perspective. Acceptability rates for EVT were 96.60% and 96.66% for the healthcare and societal perspectives. Conclusions EVT for pediatric stroke patients with LVOs resulted in added QALY and reduced lifetime costs. Based on the available data in the Save ChildS Study, EVT is very likely to be a cost-effective treatment strategy for childhood stroke.

Testicular germ cell tumours (TGCTs) respond well to cisplatin-based therapy. However, cisplatin resistance and poor outcomes do occur. It has been suggested that a shift towards DNA hypermethylation mediates cisplatin resistance in TGCT cells, although there is little direct evidence to support this claim. Here we utilized a series of isogenic cisplatin-resistant cell models and observed a strong association between cisplatin resistance in TGCT cells and a net increase in global CpG and non-CpG DNA methylation spanning regulatory, intergenic, genic and repeat elements. Hypermethylated loci were significantly enriched for repressive DNA segments, CTCF and RAD21 sites and lamina associated domains, suggesting that global nuclear reorganization of chromatin structure occurred in resistant cells. Hypomethylated CpG loci were significantly enriched for EZH2 and SUZ12 binding and H3K27me3 sites. Integrative transcriptome and methylome analyses showed a strong negative correlation between gene promoter and CpG island methylation and gene expression in resistant cells and a weaker positive correlation between gene body methylation and gene expression. A bidirectional shift between gene promoter and gene body DNA methylation occurred within multiple genes that was associated with upregulation of polycomb targets and downregulation of tumour suppressor genes. These data support the hypothesis that global remodelling of DNA methylation is a key factor in mediating cisplatin hypersensitivity and chemoresistance of TGCTs and furthers the rationale for hypomethylation therapy for refractory TGCT patients.

We replicated prior findings that a positive affect induction can improve creative performance (Baas et al., 2008) relative to a neutral control condition. We also tested whether humor improved creativity relative to both positive and neutral affect conditions. Participants were randomly assigned to either a positive, humor, or neutral affect induction condition with sets of ten memes as the mood induction stimuli. They were subsequently asked to complete two randomized divergent thinking creativity tasks. Compared to participants in the neutral condition, those in the positive affect condition generated significantly more creative ideas. The number of ideas generated by those in the humor condition did not differ from the number ideas in the positive affect condition. Implications and future directions are discussed.

Abstract Background Developing communication skills is a key competency for residents. Coaching, broadly accepted as a training modality in medical education, has been proven a successful tool for teaching communication skills. Little research is available thus far to investigate virtual coaching on communication skills for telemedicine encounters. The purpose of the study was to test the hypothesis that virtually coaching residents on communication skills is feasible and acceptable. We surveyed 21 resident-faculty pairs participating in a “fully virtual” coaching session (patient, coach, and resident were virtual). Methods We asked 50 neurology resident-faculty coach pairs to complete one “fully virtual” coaching session between May 20 and August 31, 2020. After each session, the resident and coach completed a 15-item survey, including Likert-style scale and open-ended questions, assessing feasibility and acceptability. Descriptive statistics and qualitative content and thematic analyses were performed. Results Forty-two percent (21/50) of all eligible residents completed “fully virtual” coaching sessions. The overall survey response rate was 91 % (38/42). The majority of respondents agreed that the direct observation and debriefing conversation were easy to schedule and occurred without technical difficulties and that debriefing elements (self-reflection, feedback, takeaways) were useful for residents. Ninety-five percent of respondents rated the coach’s virtual presence to be not at all disruptive to the resident-patient interaction. Virtual coaching alleviated resident stress associated with observation and was perceived as an opportunity for immediate feedback and a unique approach for resident education that will persist into the future. Conclusions In this pilot study, residents and faculty coaches found virtual coaching on communication skills feasible and acceptable for telemedicine encounters. Many elements of our intervention may be adoptable by other residency programs. For example, residents may share their communication goals with clinic faculty supervisors and then invite them to directly observe virtual encounters what could facilitate targeted feedback related to the resident’s goals. Moreover, virtual coaching on communication skills in both the in-person and telemedicine settings may particularly benefit residents in challenging encounters such as those with cognitively impaired patients or with surrogate decision-makers.

IntroductionThe COVID-19 pandemic required more responsibilities from teachers, including implementing prevention strategies, changes in school policies, and managing their own mental health, which yielded higher dissatisfaction in the field.MethodsA cross-sectional web survey was conducted among educators to collect information on their experiences teaching during the COVID-19 pandemic throughout the 2020–2021 academic year. Qualtrics, an online survey platform, fielded the survey from May 6 to June 8, 2021 to a national, convenience sample of 1,807 respondents.ResultsFindings revealed that overall, 43% of K-12 teachers reported a greater intention to leave the profession than previously recalled prior to the COVID-19 pandemic. Intention to leave was multi-level, and associated with socio-demographic factors (e.g., age: AOR = 1.87, p < 0.05), individual factors (e.g., perceived COVID risks: AOR = 1.44, p < 0.05), and teachers’ agency (e.g., dissatisfaction with school/district communications and decisions: AOR = 1.34, p < 0.05). We also found demographic disparities with respect to race and gender (e.g., female teachers: AOR: 1.78, p < 0.05) around teachers’ ability to provide feedback to schools on opening/closing and overall dissatisfaction with school/district COVID-19 prevention strategies implementation and policies.ConclusionThese findings are consistent with the Job-Demand and Resources Model (JD-R), which posits that lack of organizational support can exacerbate job stressors, leading to burnout. Specifically, dissatisfaction with the way school policies were implemented took a toll on teachers’ mental health, leading to a desire to leave the profession. These findings are also consistent with research conducted once in-person teaching resumed in 2020–2021, specifically that the COVID-19 pandemic exacerbated preexisting teacher shortages that led to self-reported issues of stress, burnout, and retention.ImplicationsFurther research is necessary to understand the resources that may be most useful to reduce the demands of teaching in the context of the COVID-19 pandemic. Some teachers are more likely to leave the field, and educational agencies may wish to target their teacher-retention efforts with emphasis on strong employee wellness programs that help educators to manage and reduce their stress. Education agency staff may wish to review policies and practices to provide meaningful opportunities to give input to school/district decisions and enable proactive communication channels.

Abstract Pediatric arterial ischemic stroke (AIS) is an uncommon emergency department (ED) presentation. We share the case of a 4‐month‐old female with a chief complaint of irritability and difficulty feeding. During ED evaluation, she developed lateral gaze deviation, tongue deviation, and rhythmic leg movements. Computed tomography of the head revealed a right‐sided hypodensity concerning for ischemic infarct without hemorrhagic conversion. Subsequent brain magnetic resonance imaging and arteriography confirmed a large right‐sided cerebral infarct and demonstrated narrowing and tortuosity of almost all extra‐ and intracranial vessels. Comprehensive pediatric AIS workup, including echocardiogram and laboratory tests for anemia, hypercoagulability, inflammatory, and genetic panels, were non‐diagnostic. This case highlights the difficulty in diagnosis of pediatric AIS due to low clinical suspicion, limited neurologic examination, and non‐specific presentations that may suggest stroke mimics. Maintenance of clinical suspicion and early recognition of pediatric AIS can result in earlier initiation of neuroprotective measures and optimization of imaging strategies for better outcomes.

Objective: To perform a pilot study to assess the efficacy of intraneural facilitation, a novel manual technique, in the treatment of carpal tunnel syndrome (CTS). Design: Patients with clinical and electrodiagnostic evidence of CTS were randomized into intraneural facilitation or sham groups. Setting: Electrodiagnostic laboratory in a university medical center. Participants: Patients referred to our electrodiagnostic laboratory were screened based on nerve conduction studies that were diagnostic for distal median neuropathy at the wrist or CTS. A total of 14 participants were enrolled; 4 participants withdrew prior to randomization, with the remaining 10 participants (N=10) divided equally between treatment and control groups. There was a 9:1 female-to-male sex ratio and average duration of symptoms was 28.5 months. Interventions: Treatment was performed twice weekly for 3 weeks. Main Outcome Measures: Primary outcomes were the Boston Carpel Tunnel Questionnaire (BCTQ) and Boston Functional Status Scale at enrollment and at 1 week and 3 months after completion of intervention. A secondary outcome was ultrasonography (US) of the median nerve performed at baseline and 1 week after intervention. Results: Ten participants completed the trial, 5 each in the treatment and 5 each in the sham groups. The total percentage change in BCTQ and Boston Functional Status Scale scores decreased at baseline, 1 week, and 3 months after intervention. However, there was no difference between control and intraneural facilitation group. Within-group differences showed nonstatistically significant differences for all the groups except for the BCTQ questionnaires after 3 months of intraneural facilitation therapy was completed (P=.043) compared with baseline. Between-group differences showed large effects for the BCTQ questionnaires (d=1.933) and wrist to forearm ratio (WFR) 1 week after completion of intervention. Conclusions: This pilot study suggests that intraneural facilitation might improve symptoms and possibly function but did not improve median nerve cross-sectional area or WFR in CTS at follow-up evaluation 3 months after completion of intervention.

OBJECTIVES:. To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN:. Prospective observational study. SETTING:. One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS:. Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS:. None. RESULTS:. Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0–81.0 yr) versus 61 years (48.0–72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, –0.84, –1.34, and –0.84; p < 0.001). CONCLUSIONS:. Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

Ardisia silvestris is a traditional medicinal herb used in Vietnam and several other countries. However, the skin-protective properties of A. silvestris ethanol extract (As-EE) have not been evaluated. Human keratinocytes form the outermost barrier of the skin and are the main target of ultraviolet (UV) radiation. UV exposure causes skin photoaging via the production of reactive oxygen species. Protection from photoaging is thus a key component of dermatological and cosmetic products. In this research, we found that As-EE can prevent UV-induced skin aging and cell death as well as enhance the barrier effect of the skin. First, the radical-scavenging ability of As-EE was checked using DPPH, ABTS, TPC, CUPRAC, and FRAP assays, and a 3-(4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay was used to examine cytotoxicity. Reporter gene assays were used to determine the doses that affect skin-barrier-related genes. A luciferase assay was used to identify possible transcription factors. The anti-photoaging mechanism of As-EE was investigated by determining correlated signaling pathways using immunoblotting analyses. As-EE had no harmful effects on HaCaT cells, according to our findings, and As-EE revealed moderate radical-scavenging ability. With high-performance liquid chromatography (HPLC) analysis, rutin was found to be one of the major components. In addition, As-EE enhanced the expression levels of hyaluronic acid synthase-1 and occludin in HaCaT cells. Moreover, As-EE dose-dependently up-regulated the production of occludin and transglutaminase-1 after suppression caused by UVB blocking the activator protein-1 signaling pathway, in particular, the extracellular response kinase and c-Jun N-terminal kinase. Our findings suggest that As-EE may have anti-photoaging effects by regulating mitogen-activated protein kinase, which is good news for the cosmetics and dermatology sectors.

The skin is the largest organ of the human body, and it is also the one most exposed to external environmental contaminants. The skin is the body’s first defense against harmful environmental stimuli, including ultraviolet B (UVB) rays and hazardous chemicals. Therefore, proper care of the skin is required to prevent skin-related diseases and age-related symptoms. In this study, we analyzed anti-aging and anti-oxidative effects of Breynia vitis-idaea ethanol extract (Bv-EE) in human keratinocytes and dermal fibroblasts. The Bv-EE had free radical scavenging activity and decreased the mRNA expression of MMPs and COX-2 in H2O2- or UVB-treated HaCaT cells. The Bv-EE also inhibited AP-1 transcriptional activity and phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, and mitogen-activated protein kinase 14 (p38), which are major AP-1 activators upon H2O2 or UVB exposure. Furthermore, the promoter activity and mRNA expression of collagen type I (Col1A1) increased in HDF cells treated with Bv-EE, and Bv-EE recovered the collagen mRNA expression decreased by H2O2 or UVB exposure. These results suggest that Bv-EE has anti-oxidative effects by inhibiting the AP-1 signaling pathway, and shows anti-aging effects by upregulating collagen synthesis.

(1) Background: Callerya atropurpurea is found in Laos, Thailand, and Vietnam. Although the anti-inflammatory action of C. atropurpurea has been investigated, the functions of this plant in allergic responses are not understood. Here, we explored the antiallergic mechanism of C. atropurpurea ethanol extract (Ca-EE) using in vitro assays and an in vivo atopic model. (2) Methods: The constituents of Ca-EE were analyzed using GC/MS. Inhibition of lipoxygenase and β-hexosaminidase activity was examined, and the expression of inflammatory genes was measured by quantitative real-time PCR. The regulatory roles of Ca-EE in IgE/FcεRI signaling were examined by Western blotting. The DNCB-induced atopic dermatitis mouse model was performed with histological analysis. (3) Results: Ca-EE comprised cis-raphasatin, lupeol, some sugars, and fatty acids. In RBL-2H3 cells, treatment with Ca-EE significantly reduced the activities of lipoxygenase and β-hexosaminidase, as well as cytokine gene expression. IgE-mediated signaling was downregulated by blocking Lyn kinases. Moreover, Ca-EE effectively inhibited allergic symptoms in the DNCB-induced atopic dermatitis model without toxicity. (4) Conclusions: Ca-EE displayed antiallergic activities through regulating IgE/Lyn signaling in RBL-2H3 cells and a contact dermatitis model. These results indicate that Ca-EE could be effective for allergic disease treatment.

Abstract Background Plants have been used as an important source of indispensable bioactive compounds in various cosmetics, foods, and medicines. However, the subsequent functional annotation of these compounds seems arduous because of the largely uncharacterized, vast metabolic repertoire of plant species with known biological phenotypes. Hence, a rapid multi-parallel screening and characterization approach is needed for plant functional metabolites. Results Fifty-one species representing three plant families, namely Asteraceae, Fabaceae, and Rosaceae, were subjected to metabolite profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultrahigh-performance liquid chromatography quadrupole orbitrap ion trap tandem mass spectrometry (UHPLC-Q-orbitrap-MS/MS) as well as multivariate analyses. Partial least squares discriminant analysis (PLS-DA) of the metabolite profiling datasets indicated a distinct clustered pattern for 51 species depending on plant parts (leaves and stems) and relative phylogeny. Examination of their relative metabolite contents showed that the extracts from Fabaceae plants were abundant in amino acids, fatty acids, and genistein compounds. However, the extracts from Rosaceae had higher levels of catechin and ellagic acid derivatives, whereas those from Asteraceae were higher in kaempferol derivatives and organic acids. Regardless of the different families, aromatic amino acids, branch chain amino acids, chlorogenic acid, flavonoids, and phenylpropanoids related to the shikimate pathway were abundant in leaves. Alternatively, certain amino acids (proline, lysine, and arginine) as well as fatty acids levels were higher in stem extracts. Further, we investigated the associated phenotypes, i.e., antioxidant activities, affected by the observed spatial (leaves and stem) and intra-family metabolomic disparity in the plant extracts. Pearson’s correlation analysis indicated that ellagic acid, mannitol, catechin, epicatechin, and quercetin derivatives were positively correlated with antioxidant phenotypes, whereas eriodictyol was positively correlated with tyrosinase inhibition activity. Conclusions This work suggests that metabolite profiling, including multi-parallel approaches and integrated bioassays, may help the expeditious characterization of plant-derived metabolites while simultaneously unraveling their chemodiversity.

Abstract Introduction Compartmental modelling is an established method of quantifying 18F-FDG uptake; however, only recently has it been applied to evaluate pulmonary inflammation. Implementation of compartmental models remains challenging in the lung, partly due to the low signal-to-noise ratio compared to other organs and the lack of standardisation. Good reproducibility is a key requirement of an imaging biomarker which has yet to be demonstrated in pulmonary compartmental models of 18F-FDG; in this paper, we address this unmet need. Methods Retrospective subject data were obtained from the EVOLVE observational study: Ten COPD patients (age =66±9; 8M/2F), 10 α 1ATD patients (age =63±8; 7M/3F) and 10 healthy volunteers (age =68±8; 9M/1F) never smokers. PET and CT images were co-registered, and whole lung regions were extracted from CT using an automated algorithm; the descending aorta was defined using a manually drawn region. Subsequent stages of the compartmental analysis were performed by two independent operators using (i) a MIAKATTM based pipeline and (ii) an in-house developed pipeline. We evaluated the metabolic rate constant of 18F-FDG (K i m ) and the fractional blood volume (V b ); Bland-Altman plots were used to compare the results. Further, we adjusted the in-house pipeline to identify the salient features in the analysis which may help improve the standardisation of this technique in the lung. Results The initial agreement on a subject level was poor: Bland-Altman coefficients of reproducibility for K i m and V b were 0.0031 and 0.047 respectively. However, the effect size between the groups (i.e. COPD, α 1ATD and healthy subjects) was similar using either pipeline. We identified the key drivers of this difference using an incremental approach: ROI methodology, modelling of the IDIF and time delay estimation. Adjustment of these factors led to improved Bland-Altman coefficients of reproducibility of 0.0015 and 0.027 for K i m and V b respectively. Conclusions Despite similar methodology, differences in implementation can lead to disparate results in the outcome parameters. When reporting the outcomes of lung compartmental modelling, we recommend the inclusion of the details of ROI methodology, input function fitting and time delay estimation to improve reproducibility.

Rationale: Early evidence for the benefit of mechanical thrombectomy (MT) in pediatric patients with intracranial large vessel occlusion has been shown in previous retrospective cohorts. Higher-level evidence is needed to overcome the limitations of these studies such as the lack of a control group and the retrospective design. Randomized trials will very likely not be feasible, and several open questions remain, for example, the impact of arteriopathic etiologies or a possible lower age limit for MT. Save ChildS Pro therefore aims to demonstrate the safety and effectiveness of MT in pediatric patients compared to the best medical management and intravenous thrombolysis.Design: Save ChildS Pro is designed as a worldwide multicenter prospective registry comparing the safety and effectiveness of MT to the best medical care alone in the treatment of pediatric arterial ischemic stroke (AIS). It will include pediatric patients (

Objective: To determine if elevated rates of autoimmune disease are present in children with both Down syndrome and moyamoya disease given the high rates of autoimmune disease reported in both conditions and unknown etiology of angiopathy in this population.Methods: A multi-center retrospective case-control study of children with Down syndrome and moyamoya syndrome, idiopathic moyamoya disease, and Down syndrome without cerebrovascular disease was performed. Outcome measures included presence of autoimmune disease, presence of autoantibodies and angiopathy severity data. Comparisons across groups was performed using the Kruskal-Wallis, χ2 and multivariate Poisson regression.Results: The prevalence of autoimmune disease were 57.7, 20.3, and 35.3% in persons with Down syndrome and moyamoya syndrome, idiopathic moyamoya disease, and Down syndrome only groups, respectively (p < 0.001). The prevalence of autoimmune disease among children with Down syndrome and moyamoya syndrome is 3.2 times (p < 0.001, 95% CI: 1.82–5.58) higher than the idiopathic moyamoya group and 1.5 times (p = 0.002, 95% CI: 1.17–1.99) higher than the Down syndrome only group when adjusting for age and sex. The most common autoimmune diseases were thyroid disorders, type I diabetes and Celiac disease. No individuals with idiopathic moyamoya disease had more than one type of autoimmune disorder while 15.4% of individuals with Down syndrome and moyamoya syndrome and 4.8% of individuals with Down syndrome only had >1 disorder (p = 0.05, 95%CI: 1.08–6.08).Interpretation: This study reports elevated rates of autoimmune disease in persons with Down syndrome and moyamoya syndrome providing a nidus for study of the role of autoimmunity in angiopathy in this population.

IMPORTANCE:. Even with its proclivity for older age, coronavirus disease 2019 has been shown to affect all age groups. However, there remains a lack of research focused primarily on the young adult population. OBJECTIVES:. To describe the epidemiology and outcomes of coronavirus disease 2019 and identify the risk factors associated with critical illness and mortality in hospitalized young adults. DESIGN, SETTINGS, AND PARTICIPANTS:. A retrospective cohort study of the Society of Critical Care Medicine’s Viral Infection and Respiratory Illness Universal Study registry. Patients 18–40 years old, hospitalized from coronavirus disease 2019 from March 2020 to April 2021, were included in the analysis. MAIN OUTCOMES AND MEASURES:. Critical illness was defined as a composite of mortality and 21 predefined interventions and complications. Multivariable logistic regression was used to assess associations with critical illness and mortality. RESULTS:. Data from 4,005 patients (152 centers, 19 countries, 18.6% non-U.S. patients) were analyzed. The median age was 32 years (interquartile range, 27–37 yr); 51% were female, 29.4% Hispanic, and 42.9% had obesity. Most patients (63.2%) had comorbidities, the most common being hypertension (14.5%) and diabetes (13.7%). Hospital and ICU mortality were 3.2% (129/4,005) and 8.3% (109/1,313), respectively. Critical illness occurred in 25% (n = 996), and 34.3% (n = 1,376) were admitted to the ICU. Older age (p = 0.03), male sex (adjusted odds ratio, 1.83 [95% CI, 1.2–2.6]), and obesity (adjusted odds ratio, 1.6 [95% CI, 1.1–2.4]) were associated with hospital mortality. In addition to the above factors, the presence of any comorbidity was associated with critical illness from coronavirus disease 2019. Multiple sensitivity analyses, including analysis with U.S. patients only and patients admitted to high-volume sites, showed similar risk factors. CONCLUSIONS:. Among hospitalized young adults, obese males with comorbidities are at higher risk of developing critical illness or dying from coronavirus disease 2019.

Aims: Orthognathic surgery corrects craniofacial and dentofacial disproportion that compromises breathing, masticatory function, and aesthetics. A patient's typology influences their psychosocial and physical pre-operative expectations and post-operative perceptions and is an emerging area of research. This study aims to evaluate subjective expectations and/or perceived outcomes of orthognathic surgery; and whether orthognathic surgery meets patient expectations. Method: A questionnaire-based cross-sectional survey was administered pre- and post-operatively. Typologically, patients were classified as metamorphosisers – those with high expectation of psychosocial and physical transformation; evolvers – opposite of metamorphosisers; pragmatists – those with low expectation of psychosocial and high expectation of physical transformation; or shedders – the opposite of pragmatists. A Chi-Square goodness fit test with p

Grewia tomentosa Juss. is a deciduous shrub that mainly grows in Asia. Despite studies of other Grewia species for treatment of various diseases, Grewia tomentosa Juss. has not been studied as a medicinal herb. This study evaluates the anti-allergic and anti-topic dermatitis activity of Grewia tomentosa Juss. ethanol extract (Gt-EE). The results show that Gt-EE suppressed IgE–antigen-induced β-hexosaminidase release. The mRNA expression of IL-1β, IL-4, IL-5, IL-6, IL-13, TNF-α, MCP-1, and TSLP, which are involved in allergic responses, was inhibited by Gt-EE in IgE-stimulated RBL-2H3 cells. In addition, the phosphorylation of Syk, PLCγ1, PKCδ, PI3K, AKT, NF-κB p65, NF-κB p50, p38, JNK, and ERK1/2 was decreased by Gt-EE in these cells. Gt-EE also showed anti-inflammatory effects in in vivo mouse models. In passive cutaneous anaphylaxis (PCA), a commonly used mouse model, Gt-EE decreased the allergic response, infiltration of mast cells, and mRNA level of IL-4. Furthermore, Gt-EE ameliorated symptoms of DNCB-induced atopic dermatitis (AD). In DNCB-induced AD, Gt-EE suppressed the increase in mast cells, serum IgE level, expression of allergic mediators (IL-1β, IL-4, IL-5, IL-6, TNF-α), and phosphorylation of proteins (IκBα, NF-κB p65, NF-κB p50, p38, JNK, and ERK1/2) implicated in allergic reactions

Maize (Zea mays subsp. mays) yield loss from arthropod herbivory is substantial. While the basis of resistance to major insect herbivores has been comparatively well-studied in maize, less is known about resistance to spider mite herbivores, which are distantly related to insects and feed by a different mechanism. Two spider mites, the generalist Tetranychus urticae, and the grass-specialist Oligonychus pratensis, are notable pests of maize, especially during drought conditions. We assessed resistance (antibiosis) to both mites of 38 highly diverse maize lines, including several previously reported to be resistant to one or the other mite species. We found that line B96, as well as its derivatives B49 and B75, were highly resistant to T. urticae. In contrast, neither these three lines, nor any others included in our study, were notably resistant to the specialist O. pratensis. Quantitative trait locus (QTL) mapping with replicate populations from crosses of B49, B75, and B96 to susceptible B73 identified a QTL in the same genomic interval on chromosome 6 for T. urticae resistance in each of the three resistant lines, and an additional resistance QTL on chromosome 1 was unique to B96. Single-locus genotyping with a marker coincident with the chromosome 6 QTL in crosses of both B49 and B75 to B73 revealed that the respective QTL was large-effect; it explained ∼70% of the variance in resistance, and resistance alleles from B49 and B75 acted recessively as compared to B73. Finally, a genome-wide haplotype analysis using genome sequence data generated for B49, B75, and B96 identified an identical haplotype, likely of initial origin from B96, as the source of T. urticae resistance on chromosome 6 in each of the B49, B75, and B96 lines. Our findings uncover the relationship between intraspecific variation in maize defenses and resistance to its major generalist and specialist spider mite herbivores, and we identified loci for use in breeding programs and for genetic studies of resistance to T. urticae, the most widespread spider mite pest of maize.

There is a growing demand for hair loss treatments with minimal side effects and recurrence potential. Connarus semidecandrus Jack has been used as a folk medicine for fever in tropical regions, but its anti-alopecia effects remain unclear. In this study, the anti-androgenic alopecia effect of an ethanol extract of Connarus semidecandrus Jack (Cs-EE) was demonstrated in a testosterone-induced androgenic alopecia (AGA) model, in terms of the hair–skin ratio, hair type frequency, and hair thickness. The area of restored hair growth and thickened hair population after Cs-EE treatment showed the hair-growth-promoting effect of Cs-EE. Histological data support the possibility that Cs-EE could reduce hair loss and upregulate hair proliferation in mouse skin by shifting hair follicles from the catagen phase to the anagen phase. Western blotting indicated that Cs-EE reduced the expression of the androgenic receptor. Cs-EE treatment also inhibited programmed cell death by upregulating Bcl-2 expression at the mRNA and protein levels. The anti-alopecia effect of Cs-EE was confirmed by in vitro experiments showing that Cs-EE had suppressive effects on 5-α reductase activity and lymph node carcinoma of the prostate proliferation, and a proliferative effect on human hair-follicle dermal papilla (HDP) cells. Apoptotic pathways in HDP cells were downregulated by Cs-EE treatment. Thus, Cs-EE could be a potential treatment for AGA.

Spontaneous splenic rupture is a rare but life-threatening complication of Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM). It occurs in less than 0.5% of cases and is the most frequent cause of death in IM. We report a case of a 13-year old female presenting with hemodynamic instability following diagnosis of EBV-induced IM. Abdominal CT was positive for grade III splenic laceration with active extravasation and exploratory laparotomy with splenectomy was performed. Postoperatively, she recovered appropriately, received vaccinations, and was discharged on postoperative day 5. Follow up has revealed no complications and return to normal activity.

Phase change material (PCM) cooling garments’ efficacy is limited by the duration of cooling provided. The purpose of this study was to evaluate the effect of replacing a PCM vest during a rest period on physiological and perceptual responses during explosive ordnance disposal (EOD) related activity. Six non-heat acclimated males undertook three trials (consisting of 2 × 3 × 16.5 min activity cycles interspersed with one 10 min rest period) in 40°C, 12% relative humidity whilst wearing a ≈38 kg EOD suit. Participants did not wear a PCM cooling vest (NoPCM); wore one PCM vest throughout (PCM1) or changed the PCM vest in the 10 min rest period (PCM2). Rectal temperature (Tre), mean skin temperature (Tskin), heart rate (HR), Physiological Strain Index (PSI), ratings of perceived exertion, temperature sensation and thermal comfort were compared at the end of each activity cycle and at the end of the trial. Data displayed as mean [95% CI]. After the rest period, a rise in Tre was attenuated in PCM2 compared to NoPCM and PCM1 (−0.57 [−0.95, −0.20]°C and −0.46 [−0.81, −0.11]°C, respectively). A rise in HR and Tskin was also attenuated in PCM2 compared to NoPCM and PCM1 (−23 [−29, −16] beats⋅min–1 and −17 [−28, −6.0] beats⋅min–1; −0.61 [−1.21, −0.10]°C and −0.89 [−1.37, −0.42]°C, respectively). Resulting in PSI being lower in PCM2 compared to NoPCM and PCM1 (−2.2 [−3.1, −1.4] and –0.8 [−1.3,−0.4], respectively). More favorable perceptions were also observed in PCM2 vs. both NoPCM and PCM1 (p < 0.01). Thermal perceptual measures were similar between NoPCM and PCM1 and the rise in Tre after the rest period tended to be greater in PCM1 than NoPCM. These findings suggest that replacing a PCM vest better attenuates rises in both physiological and perceptual strain compared to when a PCM vest is not replaced. Furthermore, not replacing a PCM vest that has exhausted its cooling capacity, can increase the level of heat strain experienced by the wearer.

Background: The differential diagnosis for women who present with a vaginal mass after undergoing a hysterectomy is dependent on the indication, type and timing of the hysterectomy. The differential diagnosis includes cervical dysplasia, malignancy, nabothian cysts, prolapsed endocervical polyp/fibroid, abscess, hematoma, granulation tissue, or dehiscence with organ evisceration. Case: We introduce a case of a woman who presented with a vaginal apex mass and had a remote history of a total hysterectomy for an unknown indication. She was ultimately diagnosed with high grade serous carcinoma of a prolapsed fallopian tube. Conclusion: This is the first reported case of serous carcinoma of a prolapsed fallopian tube and highlights the importance of maintaining a wide differential diagnosis for women who present with vaginal apex masses.

ObjectiveHypotension following endotracheal intubation in the ICU is associated with poor outcomes. There is no formal prediction tool to help estimate the onset of this hemodynamic compromise. Our objective was to derive and validate a prediction model for immediate hypotension following endotracheal intubation.MethodsA multicenter, prospective, cohort study enrolling 934 adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 was conducted to derive and validate a prediction model for immediate hypotension following endotracheal intubation. We defined hypotension as: 1) mean arterial pressure ResultsPost-intubation hypotension developed in 344 (36.8%) patients. In the full cohort, 11 variables were independently associated with hypotension: increasing illness severity; increasing age; sepsis diagnosis; endotracheal intubation in the setting of cardiac arrest, mean arterial pressure ConclusionsA novel multivariable risk score predicted post-intubation hypotension with accuracy in both unstable and stable critically ill patients.Study registrationClinicaltrials.gov identifier: NCT02508948 and Registered Report Identifier: RR2-10.2196/11101.

Abstract Background The U.S. Centers for Disease Control and Prevention (CDC) develops tools to support implementation of evidence-based interventions for school health. To advance understanding of factors influencing the use of these implementation tools, we conducted an evaluation of state, school district, and local school staffs’ use of four CDC tools to support implementation of physical activity, nutrition, health education, and parent engagement. Two frameworks guided the evaluation: Interactive Systems Framework (ISF) for Dissemination and Implementation and Consolidated Framework for Implementation Research (CFIR). Methods The evaluation applied a mixed methods, cross-sectional design that included online surveys (n = 69 state staff from 43 states), phone interviews (n = 13 state staff from 6 states), and in-person interviews (n = 90 district and school staff from 8 districts in 5 states). Descriptive analyses were applied to surveys and content analysis to interviews. Results The survey found that the majority of state staff surveyed was aware of three of the CDC tools but most were knowledgeable and confident in their ability to use only two. These same two tools were the ones for which states were most likely to have provided training and technical assistance in the past year. Interviews provided insight into how tools were used and why use varied, with themes organized within the ISF domain “support strategies” (e.g., training, technical assistance) and four CFIR domains: (1) characteristics of tools, (2) inner setting, (3) outer setting, and (4) individuals. Overall, tools were valued for the credibility of their source (CDC) and evidence strength and quality. Respondents reported that tools were too complex for use by school staff. However, if tools were adaptable and compatible with inner and outer setting factors, state and district staff were willing and able to adapt tools for school use. Conclusions Implementation tools are essential to supporting broad-scale implementation of evidence-based interventions. This study illustrates how CFIR and ISF might be applied to evaluate factors influencing tools’ use and provides recommendations for designing tools to fit within the multi-tiered systems involved in promoting, supporting, and implementing evidence-based interventions in schools. Findings have relevance for the design of implementation tools for use by other multi-tiered systems.

An ethanol extract (Pd-EE) of Pinus densiflora Siebold and Zucc was derived from the branches of pine trees. According to the Donguibogam, pine resin has the effects of lowering the fever, reducing pain, and killing worms. The purpose of this study is to investigate whether Pd-EE has anti-inflammatory effects. During in vitro trials, NO production, as well as changes in the mRNA levels of inflammation-related genes and the phosphorylation levels of related proteins, were confirmed in RAW264.7 cells activated with lipopolysaccharide depending on the presence or absence of Pd-EE treatment. The activities of transcription factors were checked in HEK293T cells transfected with adapter molecules in the inflammatory pathway. The anti-inflammatory efficacy of Pd-EE was also estimated in vivo with acute gastritis and acute lung injury models. LC-MS analysis was conducted to identify the components of Pd-EE. This extract reduced the production of NO and the mRNA expression levels of iNOS, COX-2, and IL-6 in RAW264.7 cells. In addition, protein expression levels of p50 and p65 and phosphorylation levels of FRA1 were decreased. In the luciferase assay, the activities of NF-κB and AP-1 were lowered. In acute gastritis and acute lung injury models, Pd-EE suppressed inflammation, resulting in alleviated damage.

Many indigenous Korean plants have been used in medicinal preparations and health-promoting foods. These plant species contain beneficial metabolites with various bioactivities, such as antioxidant and anti-inflammatory activities. Herein, we suggest a new screening strategy using metabolomics to explore the bioactive compounds in 50 Korean plants. Secondary metabolites were analyzed using UHPLC-LTQ-Orbitrap-MS/MS. The plant extracts were subjected to antioxidant and anti-inflammatory assays. We identified metabolites that contributed to bioactivities according to the results of bioassays and multivariate analyses. Using Pearson’s correlation, phenolics (e.g., casuarictin, 3-O-methylellagic acid) showed positive correlation with antioxidant activity, while biflavonoids (e.g., amentoflavone, rosbustaflavone) were correlated with nitric oxide (NO) inhibition activity. To compensate for the limitation of this new strategy, we further validated these by investigating three parts (branches, fruits, leaves) of Platycladus orientalis which showed high activities on both bioassays. Unlike the above observation, we identified significantly different metabolites from different parts, which was not the results of bioassays. In these validation steps, interestingly, biflavonoids (e.g., robustaflavone, sciadopitysin) contributed to both activities in P. orientalis. The findings of this work suggest that new strategy could be more beneficial in the identification of bioactive plant species as well as that of their corresponding bioactive compounds that impart the bioactivity.

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

This article demonstrates evidence of context-related style-shifting on YouTube. This was achieved by comparing the vowels of vlogger Phil Lester in multiple contexts (a solo vlog, collaborative vlog, gaming video, and live video). A mixed-model regression found significant differences between the more scripted solo vlog context and the less scripted gaming and live videos: in the former, Lester’s FOOT/STRUT merger was reduced, and in the latter he showed considerable variability in his employment of the TRAP/BATH split. It is argued that this results from greater attention paid to level aspects of his Northern accent for an international audience.

Linusorbs (LOs) are natural peptides found in flaxseed oil that exert various biological activities. Of LOs, LOB3 ([1–9-NαC]-linusorb B3) was reported to have antioxidative and anti-inflammatory activities; however, its anti-cancer activity has been poorly understood. Therefore, this study investigated the anti-cancer effect of LOB3 and its underlying mechanism in glioblastoma cells. LOB3 induced apoptosis and suppressed the proliferation of C6 cells by inhibiting the expression of anti-apoptotic genes, B cell lymphoma 2 (Bcl-2) and p53, as well as promoting the activation of pro-apoptotic caspases, caspase-3 and -9. LOB3 also retarded the migration of C6 cells, which was achieved by suppressing the formation of the actin cytoskeleton critical for the progression, invasion, and metastasis of cancer. Moreover, LOB3 inhibited the activation of the proto-oncogene, Src, and the downstream effector, signal transducer and activator of transcription 3 (STAT3), in C6 cells. Taken together, these results suggest that LOB3 plays an anti-cancer role by inducing apoptosis and inhibiting the migration of C6 cells through the regulation of apoptosis-related molecules, actin polymerization, and proto-oncogenes.

Patrinia villosa (Thunb.) Juss is a traditional herb commonly used in East Asia including Korea, Japan, and China. It has been administered to reduce and treat inflammation in Donguibogam, Korea. The mechanism for its anti-inflammatory effects has already been reported. In this study, we confirmed the efficacy of Patrinia villosa (Thunb.) Juss ethanol extract (Pv-EE) for inducing autophagy and investigate its anti-melanogenic properties. Melanin secretion and content were investigated using cells from the melanoma cell line B16F10. Pv-EE inhibited melanin in melanogenesis induced by α-melanocyte-stimulating hormone (α-MSH). The mechanism of inhibition of Pv-EE was confirmed by suppressing the mRNA of microphthalmia-associated transcription factor (MITF), decreasing the phosphorylation level of CREB, and increasing the phosphorylation of ERK. Finally, it was confirmed that Pv-EE induces autophagy through the autophagy markers LC3B and p62, and that the anti-melanogenic effect of Pv-EE is inhibited by the autophagy inhibitor 3-methyl adenine (3-MA). These results suggest that Pv-EE may be used as a skin protectant due to its anti-melanin properties including autophagy.

ABSTRACT BACKGROUND: Multiple myeloma is a plasma cell neoplasm with acquired genetic abnormalities of clinical and prognostic importance. Multiple myeloma differs from other hematologic malignancies due to a high fraction of low proliferating malignant plasma cells and the paucity of plasma cells in bone marrow aspiration samples, making cytogenetic analysis a challenge. An abnormal karyotype is found in only one-third of patients with multiple myeloma and interphase fluorescence in situ hybridization is the most useful test for studying the chromosomal abnormalities present in almost 90% of cases. However, it is necessary to study the genetic abnormalities in plasma cells after their identification or selection by morphology, immunophenotyping or sorting. Other challenges are the selection of the most informative FISH panel and determining cut-off levels for FISH probes. This study reports the validation of interphase fluorescence in situ hybridization using CD138 positive cells, according to proposed guidelines published by the European Myeloma Network (EMN) in 2012. METHOD: Bone marrow samples from patients with multiple myeloma were used to standardize a panel of five probes [1q amplification, 13q14 deletion, 17p deletion, t(4;14), and t(14;16)] in CD138+ cells purified by magnetic cell sorting. RESULTS: This test was validated with a low turnaround time and good reproducibility. Five of six samples showed genetic abnormalities. Monosomy/deletion 13 plus t(4;14) were found in two cases. CONCLUSION: This technique together with magnetic cell sorting is effective and can be used in the routine laboratory practice. In addition, magnetic cell sorting provides a pure plasma cell population that allows other molecular and genomic studies.

Chemotaxonomic metabolite profiling of 62 indigenous Korean plant species was performed by ultrahigh performance liquid chromatography (UHPLC)-linear trap quadrupole-ion trap (LTQ-IT) mass spectrometry/mass spectrometry (MS/MS) combined with multivariate statistical analysis. In partial least squares discriminant analysis (PLS-DA), the 62 species clustered depending on their phylogenetic family, in particular, Aceraceae, Betulaceae, and Fagaceae were distinguished from Rosaceae, Fabaceae, and Asteraceae. Quinic acid, gallic acid, quercetin, quercetin derivatives, kaempferol, and kaempferol derivatives were identified as family-specific metabolites, and were found in relatively high concentrations in Aceraceae, Betulaceae, and Fagaceae. Fagaceae and Asteraceae were selected based on results of PLS-DA and bioactivities to determine the correlation between metabolic differences among plant families and bioactivities. Quinic acid, quercetin, kaempferol, quercetin derivatives, and kaempferol derivatives were found in higher concentrations in Fagaceae than in Asteraceae, and were positively correlated with antioxidant and tyrosinase inhibition activities. These results suggest that metabolite profiling was a useful tool for finding the different metabolic states of each plant family and understanding the correlation between metabolites and bioactivities in accordance with plant family.

Hemorrhagic strokes account for half of all strokes seen in children, and the etiologies of these hemorrhagic strokes differ greatly from those seen in adult patients. This review gives an overview about incidence and etiologies as well as presentation of children with intracerebral hemorrhage and with differential diagnoses in the emergency department. Most importantly it describes how neuroimaging of children with intracerebral hemorrhage should be tailored to specific situations and clinical contexts and recommends specific imaging protocols for acute and repeat imaging. In this context it is important to keep in mind the high prevalence of underlying vascular lesions and adapt the imaging protocol accordingly, meaning that vascular imaging plays a key role regardless of modality. Magnetic resonance imaging (MRI), including advanced sequences, should be favored whenever possible at the acute phase.

Endocrine disrupting chemicals (EDCs) disrupt the physiological metabolism, thus playing an important role in the development of obesity. EDCs, the so-called ‘obesogens’, might predispose some individuals to gain weight. This study investigated the effects of bisphenol A (BPA) and its alternatives (BPS and BPF) on adipocyte differentiation and the effects of the leaves of Potentilla rugulosa Nakai extract (LPE) as a functional food ingredient on obesogen-induced lipid production and adipogenesis in 3T3-L1 cells. The results showed that LPE has high total phenolic and flavonoid contents (77.58 ± 0.57 mg gallic acid equivalents (GAE)/g and 57.31 ± 1.72 mg quercetin equivalents (QE)/g, respectively). In addition, LPE exerted significant antioxidant effects in terms of DPPH radical scavenging activity, reducing power, ferric-ion reducing antioxidant power, and oxygen radical absorbance capacity. BPA, BPS, and BPF increased lipid accumulation, protein expressions of adipogenic transcription factors (PPAR-γ, C/EBP-α, and aP2), and reactive oxygen species (ROS) production in 3T3-L1 cells. However, LPE suppressed the BPA-, BPS-, and BPF-induced effects on adipogenesis. Therefore, LPE has potential as a functional food supplement that can prevent bisphenol-induced lipid metabolism disorders.

While substantial progress has been made in understanding defense responses of cereals to insect herbivores, comparatively little is known about responses to feeding by spider mites. Nevertheless, several spider mite species, including the generalist Tetranychus urticae and the grass specialist Oligonychus pratensis, cause damage on cereals such as maize and wheat, especially during drought stress. To understand defense responses of cereals to spider mites, we characterized the transcriptomic responses of maize and barley to herbivory by both mite species, and included a wounding control against which modulation of defenses could be tested. T. urticae and O. pratensis induced highly correlated changes in gene expression on both maize and barley. Within 2 h, hundreds of genes were upregulated, and thousands of genes were up- or downregulated after 24 h. In general, expression changes were similar to those induced by wounding, including for genes associated with jasmonic acid biosynthesis and signaling. Many genes encoding proteins involved in direct defenses, or those required for herbivore-induced plant volatiles, were strongly upregulated in response to mite herbivory. Further, biosynthesis genes for benzoxazinoids, which are specialized compounds of Poaceae with known roles in deterring insect herbivores, were induced in maize. Compared to chewing insects, spider mites are cell content feeders and cause grossly different patterns of tissue damage. Nonetheless, the gene expression responses of maize to both mite herbivores, including for phytohormone signaling pathways and for the synthesis of the benzoxazinoid 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside, a known defensive metabolite against caterpillars, resembled those reported for a generalist chewing insect, Spodoptera exigua. On maize plants harboring mutations in several benzoxazinoid biosynthesis genes, T. urticae performance dramatically increased compared to wild-type plants. In contrast, no difference in performance was observed between mutant and wild-type plants for the specialist O. pratensis. Collectively, our data provide little evidence that maize and barley defense responses differentiate herbivory between T. urticae and O. pratensis. Further, our work suggests that the likely route to specialization for O. pratensis involved the evolution of a robust mechanism to cope with the benzoxazinoid defenses of its cereal hosts.

Plants are an important and inexhaustible source of bioactive molecules in food, medicine, agriculture, and industry. In this study, we performed systematic liquid chromatography-mass spectrometry (LC-MS)-based metabolic profiling coupled with antioxidant assays for indigenous plant family extracts. Partial least-squares discriminant analysis of LC-MS datasets for the extracts of 34 plant species belonging to the families Aceraceae, Asteraceae, and Rosaceae showed that these species were clustered according to their respective phylogenies. In particular, seven Aceraceae species were clearly demarcated with higher average antioxidant activities, rationalizing their application for bioconversion studies. On the basis of further evaluation of the interspecies variability of metabolic profiles and antioxidant activities among Aceraceae family plants, we found that Acer tataricum (TA) extracts were clearly distinguished from those of other species, with a higher relative abundance of tannin derivatives. Further, we detected a strong positive correlation between most tannin derivatives and the observed higher antioxidant activities. Following Aspergillus oryzae-mediated fermentative bioconversion of Acer plant extracts, we observed a time-correlated (0-8 days) linear increase in antioxidant phenotypes for all species, with TA having the highest activity. Temporal analysis of the MS data revealed tannin bioconversion mechanisms with a relatively higher abundance of gallic acid (m/z 169) accumulated at the end of 8 days, particularly in TA. Similarly, quercetin precursor (glycoside) metabolites were also transformed to quercetin aglycones (m/z 301) in most Acer plant extracts. The present study underscores the efficacy of fermentative bioconversion strategies aimed at enhancing the quality and availability of bioactive metabolites from plant extracts.

Nine varieties of pigmented rice (Oryza sativa L.) seeds that were black, red, or white were used to perform metabolite profiling by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography (GC) TOF-MS, to measure antioxidant activities. Clear grouping patterns determined by the color of the rice seeds were identified in principle component analysis (PCA) derived from UPLC-Q-TOF-MS. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimer, proanthocyanidin trimer, apigenin-6-C-glugosyl-8-C-arabiboside, tricin-O-rhamnoside-O-hexoside, and lipids were identified as significantly different secondary metabolites. In PCA score plots derived from GC-TOF-MS, Jakwangdo (JKD) and Ilpoom (IP) species were discriminated from the other rice seeds by PC1 and PC2. Valine, phenylalanine, adenosine, pyruvate, nicotinic acid, succinic acid, maleic acid, malonic acid, gluconic acid, xylose, fructose, glucose, maltose, and myo-inositol were significantly different primary metabolites in JKD species, while GABA, asparagine, xylitol, and sucrose were significantly distributed in IP species. Analysis of antioxidant activities revealed that black and red rice seeds had higher activity than white rice seeds. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimers, proanthocyanidin trimers, and catechin were highly correlated with antioxidant activities, and were more plentiful in black and red rice seeds. These results are expected to provide valuable information that could help improve and develop rice-breeding techniques.

Plant species have traditionally been revered for their unparalleled pharmacognostic applications. We outline a non-iterative multi-parallel metabolomic-cum-bioassay-guided methodology toward the functional characterization of ethanol extracts from the Betulaceae family plants (n = 10). We performed mass spectrometry (MS)-based multivariate analyses and bioassay-guided (ABTS antioxidant activity and cytoprotective effects against H2O2-induced cell damage) analyses of SPE fractions. A clearly distinct metabolomic pattern coupled with significantly higher bioactivities was observed for 40% methanol SPE eluate. Further, the 40% SPE eluate was subjected to preparative high-performance liquid chromatography (prep-HPLC) analysis, yielding 72 sub-fractions (1 min−1), with the highest antioxidant activities observed for the 15 min and 31 min sub-fractions. We simultaneously performed hyphenated-MS-based metabolite characterization of bioactive components for both the 40% methanol SPE fraction and its prep-HPLC sub-fraction (15 min and 31 min). Altogether, 19 candidate metabolites were mainly observed to contribute toward the observed bioactivities. In particular, ethyl gallate was mainly observed to affect the antioxidant activities of SPE and prep-HPLC fractions of Alnus firma extracts. We propose an integrated metabolomic-cum-bioassay-guided approach for the expeditious selection and characterization of discriminant metabolites with desired phenotypes or bioactivities.