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Skin aging is associated with increased reactive oxygen species (ROS) produced by human cells. These radicals are the main causes of skin aging, and skin cells have developed antioxidant enzymes for protection against ROS-induced damage. Antioxidants play critical roles to prevent ROS-induced aging symptoms. In this study, the antioxidant properties of Pourthiaea villosa (Thunb.) Decne. extract (PVDE) were studied. Human dermal fibroblast (HDF) cells were treated with PVDE to evaluate its antioxidant and antiaging activities and to investigate the underlying mechanisms. The identified compounds were polyols, and phenolic and flavonoid compounds from PVDE by UHPLC-LTQ-IT-MS/MS. PVDE exhibited significant antioxidant effects, as evaluated with reducing power, and ABTS and DPPH radical scavenging activity. Furthermore, PVDE treatment significantly increased antioxidant enzyme expressions and effectively blocked H2O2-induced matrix metalloproteinase activity through MAPK signaling pathways in HDFs. Therefore, these results showed that PVDE affords an advantage of being a functional natural material with antioxidant and antiaging effects for the skin.

Islet transplantation has been shown to restore normoglycemia in animal models and for type 1 diabetic patients in clinical trials. One method of storing islets intended for transplantation is via cryobanking at very low temperatures (−196 °C). Cryobanking islets without the use of cryoprotecting agents (CPAs) contributes to cellular shear stress and cell death. Although current CPA protocols vary, high concentrations of these agents are toxic to islets cells. This study tested the effects of the permeating CPA dimethyl sulfoxide (Me2SO) with the addition of ethylene glycol (EG), both at reduced concentrations, on rat and human islet cell yield, viability, and glucose stimulated insulin release (GSIR). To test this, islets were treated using three combinations of CPAs (2M ME2SO, 1M ME2SO + 1M EG, and 1M ME2SO + 0.5M EG). Next, fresh islets, 2M ME2SO islets, and 1M ME2SO + 0.5M EG isolated rat islets were transplanted into streptozotocin-induced (STZ) diabetic mice. Our data showed that cryopreservation with a reduced concentration of ME2SO (1M ME2SO + multimolar EG) achieved a higher percent yield and viability when compared to the current standard 2M ME2SO treatment for both rat and human islets. Furthermore, STZ-induced diabetic mice achieved normoglycemia after transplantation with 1000 islet equivalents (IE), an average 12 days sooner, with islets cryopreserved with reduced-concentration (ME2SO + 0.5M EG), compared to islets preserved with 2M ME2SO. In conclusion, reduced concentration of penetrating CPAs during islet cryopreservation increases islet yield and viability in vitro and reduces delay before normoglycemia in diabetic mice.

BackgroundThe extended time window for endovascular therapy in adult stroke represents an opportunity for stroke treatment in children for whom diagnosis may be delayed. However, selection criteria for pediatric thrombectomy has not been defined.MethodsWe performed a retrospective cohort study of patients aged ResultsTwelve children were included: 8/12 (66.7%) were female, mean age 9.7±5.0 years, median National Institutes of Health Stroke Scale (NIHSS) 11.5 (IQR 10–14). Stroke etiology was cardioembolic in 75%, dissection in 16.7%, and cryptogenic in 8.3%. For 2/5 with perfusion imaging, Tmax >4 s appeared to better correlate with NIHSS. Nine patients (75%) were treated: seven underwent thrombectomy alone; one received IV alteplase and thrombectomy, and one received IV alteplase alone. Favorable outcome was achieved in 78% of treated patients versus 0% of untreated patients (P=0.018). All untreated patients had poor outcome, with death (n=2) or severe disability (n=1) at follow-up. Among treated patients, older children (12.8±2.9 vs 4.2±5.0 years, P=0.014) and children presenting as outpatient (100% vs 0%, P=0.028) appeared to have better outcomes.ConclusionsPerfusion imaging is feasible in pediatric stroke and may help identify salvageable tissue in extended time windows, though penumbral thresholds may differ from adult values. Further studies are needed to define criteria for thrombectomy in this unique population.

Introduction Increased use of opioids has led to higher rates of overdose and hospital admissions. Studies in trauma populations have focused on outcomes associated with acute intoxications rather than addiction. We hypothesize that clinical outcomes after injury would be inferior for opioid-dependent patients compared to opioid-naive patients. Methods We identified all opioid-dependent adult patients admitted to an academic level I trauma center in 2016 with an Injury Severity Score (ISS) ≥ 5. Patients were further categorized by their pattern of opioid dependency into prescription abuse, illicit abuse, or chronic pain subgroups. Outcome measures included length of stay (LOS), major complications, mortality, non-home discharge, ventilator days, and readmissions. Regression models were adjusted for patient demographics, insurance, ISS, and comorbidities. Results Of the 1450 patients who met the inclusion criteria, 18% were opioid-dependent. Among opioid-dependent patients, 30%, 27%, and 43% were prescription abuse, illicit abuse, and chronic pain patients, respectively. Compared to opioid-naive (non-users) patients, opioid-dependent patients had longer LOS, more ventilator days, more non-home discharges, and higher readmission rates. Subgroup analysis revealed significant differences among all cohorts when compared to non-users in LOS, non-home discharge, readmissions, and major complications. Opioid dependency was not associated with mortality. Conclusion Opioid dependency was detected in 18% of trauma patients and was independently associated with inferior outcomes. The impact of opioid dependency affects each opioid subgroup differently with all cohorts demonstrating increased 30-day readmissions. Opioid dependent patients may be targeted for risk interventions to reduce LOS, non-home discharge, complications and readmissions.

e18029 Background: Patients with recurrent or metastatic nasopharyngeal cancer (R/M NPC) who failed platinum-based chemotherapy have poor prognoses. We report the clinical activity and safety of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor (TGF)-βRII receptor fused to a human IgG1 antibody blocking programmed death-ligand 1 (PD-L1), in patients with heavily pretreated R/M NPC. Tumor and plasma-based biomarkers were investigated in an exploratory analysis. Methods: Eligible patients had histologically confirmed NPC that had recurred at distant sites and were not amenable to curative treatment. All patients received at least one prior line of platinum-based chemotherapy for recurrent disease. Patients were treated with bintrafusp alfa (1200mg every 2 weeks) until disease progression. The sample size was estimated to assume a 40% objective response rate (ORR) to bintrafusp alfa compared with 20% for checkpoint inhibitors. Modified Simon two-stage optimal design was used (power, 80%; a = 0.05; P0 = 0.20; P1 = 0.40; n1 = 18; n = 33 with an additional five patients to allow for ineligibility or other reasons). The primary endpoint was ORR and secondary endpoints included survival and toxicity. Expression of PD-L1 in archived tumors, plasma clearance of Epstein-Barr virus (EBV) DNA, plasma clearance of TGF-β, and exosomal PD-L1 were assessed for a potential correlation with ORR. (NCT 04396886). Results: Out of 43 patients screened, 38 patients were enrolled. After a median follow-up of 14.9 months (range: 1.6-23.3 months), the confirmed ORR was 23.7% (95% CI: 12.4-38.8%) (complete response, n = 1; partial response, n = 8). The median treatment duration was 1.8 months (range: 0.5-14.3 months). 8 patients (21.1%) and 2 patients (5.3%) received bintrafusp alfa for > 6 months and > 12 months respectively. The 1-year overall survival (OS) rate was 57.5% (95% CI, 40.2% to 71.5%) and 1-year progression-free survival rate was 23% (95% CI, 10.1% to 39.4%). ORR was higher in patients with a decreasing trend in EBV-DNA at week 4 (40% vs. 6.3%, p = 0.02), whereas high exosomal PD-L1 levels at week 4 were predictive of worse ORR (5.3% vs. 41.7%, p = 0.012). There were no associations between clinical outcome and tissue PD-L1 expression (p = 0.952) or plasma TGF-β clearance (p = 0.28). 16 patients (42.4%) experienced ≥ grade 3 treatment-related adverse events, most commonly anemia (n = 9, 23.7%) and secondary malignancies (n = 4, 10.5%). Conclusions: Bintrafusp alfa has promising activity in heavily pretreated R/M NPC and a favorable 1-year OS rate, though the observed activity was not as high as the study initially aimed. The biomarker results warrant validation in larger cohorts. Clinical trial information: NCT04396886.

Food insecurity negatively impacts the health and well-being of postsecondary students attending college and university. Students may be especially vulnerable for food insecurity if they care for c...

Unschooling is a form of homeschooling in which parents allow children to self-direct their education. To determine if there was any evidence of unschoolers attending to the goals of multicultural education, we conducted a content analysis of a germinal resource—the 1977-1981 issues of Growing Without Schooling (GWS). Our analysis revealed that, in the early years, the content of this magazine depicted some degree of exposure to issues of oppression related to race, gender, and social class, but relatively rare engagement from the perspective of the marginalized, and minimal focus on taking social action to mitigate societal inequities.

Ethnopharmacological relevance Activated astrocytes are involved in the progression of neurodegenerative diseases. Traditionally, Ailanthus altissima (Mill.) Swingle, widely distributed in East Asia, has been used as a medicine for the treatment of fever, gastric diseases, and inflammation. Although A. altissima has been reported to play an anti-inflammatory role in peripheral tissues or cells, its role in the central nervous system (CNS) remains unclear. Aim of the study In the present study, we investigated the anti-inflammatory effects and mechanism of action of A. altissima in primary astrocytes stimulated by lipopolysaccharide (LPS). Materials and methods A nitrite assay was used to measure nitric oxide (NO) production, and the tetrazolium salt 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to determine cytotoxicity. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) were determined with western blotting. Reverse-transcription PCR was used to assess the expression of inflammatory cytokines. The levels of reactive oxygen species were measured using 2,7-dichlorodihydrofluorescein diacetate. Luciferase assay and immunocytochemistry were used for assessing nuclear factor-kappa B (NF-κB) transcription and p65 localization, respectively. Memory and social interaction were analyzed using the Y-maze and three-chamber tests, respectively. Results The ethanol extract of A. altissima leaves (AAE) inhibited iNOS and COX-2 expression in LPS-stimulated astrocytes. Moreover, AAE reduced the transcription of various proinflammatory mediators, hindered NF-κB activation, and suppressed extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activation without p38 activation. Ultra-high performance liquid chromatography with mass spectrometry analysis revealed that AAE comprised ethyl gallate, quercetin, and kaempferol, along with luteolin, which has anti-inflammatory properties, and repressed LPS-induced nitrite levels and the nuclear translocation of p65. Finally, oral administration of AAE attenuated LPS-induced memory and social impairment in mice and repressed LPS-induced ERK and JNK activation in the cortices of mice. Conclusion AAE could have therapeutic uses in the treatment of neuroinflammatory diseases via suppression of astrocyte activation.

The abundances of free-living species have changed dramatically in recent decades, but little is known about change in the abundance of parasitic species. We investigated whether populations of several parasites have shifted over time in two shore crab hosts, Hemigrapsus oregonensis and Hemigrapsus nudus, by comparing the prevalence and abundance of three parasite taxa in a historical dataset (1969–1970) to contemporary parasite abundance (2018–2020) for hosts collected from 11 intertidal sites located from Oregon, USA, to British Columbia, Canada. Our data suggest that the abundance of the parasitic isopod Portunion conformis has varied around a stable mean for the past 50 years. No change over time was observed for larval acanthocephalans. However, larval microphallid trematodes increased in prevalence over time among H. oregonensis hosts, from a mean of 8.4–61.8% between the historical and contemporary time points. The substantial increase in the prevalence of larval microphallid trematodes could be owing to increased abundances of their bird final hosts, increased production of parasite infective stages by snail intermediate hosts or both. Our study highlights the variability among parasite species in their temporal trajectories of change.

This special issue was inspired by recent developments within community sport which has seen a continual redefinition of the roles and responsibilities of community sports organisations. Central to these developments has been the increasing demand upon organisations to be held accountable in relation to their various funding agreements and the requirement to evidence a return on the investment given by multiple stakeholders (Brookes & Wiggan, 2009; Collins, 2010). At its core, community sport development is about addressing social inequalities and the need to understand and challenge these issues with society (Bloyce & Smith, 2013; Hylton & Totten, 2013; Mackintosh, 2011, 2020). Our intent has been to provide a special issue which offers insight into best practice examples of the management of change and measurement of impact within community sport across a wider variety of organisations and settings to address these issues (Hylton & Totten, 2013).

Pinus thunbergii Parl. (PTP) has traditionally been used for edible and medicinal purposes to treat several disorders, including diabetes and neuralgia. Therefore, this study sought to evaluate the inhibitory effects of PTP leaf ethanol extracts on acute inflammation. Moreover, the reactive oxygen species (ROS) scavenging activity, superoxide dismutase (SOD) activity, lipopolysaccharide (LPS)-induced nitric oxide (NO) generation, and H2O2-induced lipid peroxidation capacity of PTP were assessed in vitro in RAW 264.7 macrophages. Our results suggest that PTP prevents cell damage caused by oxidative free radicals and downregulates the expression of LPS-induced inflammation-associated factors including inducible nitric oxidase synthetase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). PTP inhibited NO production by 53.5% ( P < 0.05 ) and iNOS expression by 71.5% ( P < 0.01 ) at 100 µg/mL. PTP at 100 µg/mL also inhibited ROS generation by 58.2% ( P < 0.01 ) and SOD activity by 29.3%, as well as COX-2 expression by 83.3% ( P < 0.01 ) and PGE2 expression by 98.6% ( P < 0.01 ). The anti-inflammatory effects of PTP were confirmed in vivo using an arachidonic acid (AA)-induced ear edema mouse model. Ear thickness and myeloperoxidase (MPO) activity were evaluated as indicators of inflammation. PTP inhibited edema formation by 64.5% ( P < 0.05 ) at 1.0 mg/ear. A total of 16 metabolites were identified in PTP extracts and categorized into subgroups, including two phenolic acids (mainly quinic acid), seven flavonoids, five lignans, one sesquiterpenoid, and one long-chain fatty acid. Therefore, our results suggest that PTP possesses anti-inflammatory properties.

The Alberta Stroke Program Early CT Score (ASPECTS) is a quick and reliable semiquantitative tool to estimate the size of an acute ischemic infarct on a noncontrast head CT.1 Ten brain regions in the middle cerebral artery territory are evaluated, with 1 point subtracted for each infarcted region; total scores range from 0 to 10. Lower ASPECTS, indicating larger infarct burden, has been associated with higher risk of hemorrhagic transformation and worse outcomes in adult patients with stroke2 and is one criterion considered in the assessment of eligibility for thrombectomy. A version of this scoring system, the modified pediatric ASPECTS (modASPECTS), was developed to measure infarct size in children using diffusion-weighted sequences on MRI.3 For modASPECTS, 30 regions are scored, including areas of the anterior and posterior cerebral artery territories in addition to the middle cerebral artery territory.4 One point is added for each area involved, resulting in a score from 0 to 30, with higher scores indicating more areas of infarct.

Objectives: To characterize the effect that a ban on elective surgery had for patients who were scheduled for surgery with a gynecologic oncologist during the first coronavirus disease 19 (COVID-19) outbreak in New York City. Methods: Patients who were scheduled to undergo surgery by a gynecologic oncologist at one of three campuses of a New York City based academic hospital during the ban on elective surgery between March 16, 2020 and June 15, 2020 were included. Patients with benign disease were excluded. Data on patient demographics, perioperative characteristics, nature of surgical delay, and post-operative treatment were abstracted from patient charts. Standard of care was considered met if surgical procedures occurred for suspected malignant and pre-invasive disease, or if an appropriate treatment plan and follow up was documented for malignant cases. Kruskal-Wallis and chi-square test of independence were performed with significance set at p Results: A total of 196 patients were scheduled to undergo a surgical procedure during the ban on elective surgery, of which 146 were for malignant, suspected malignant or pre-invasive disease. The majority of cases (42.4%) occurred in patients with known malignancy, followed by suspected malignancy (37.7%) and pre-invasive disease (19.9%). Forty percent of patients experienced one or more surgical delay, 9.6% experienced 2 or more surgical delays and 1.4% experienced three or more surgical delays. Of patients who experienced surgical delays, 75.9% experienced hospital-initiated delays and 24.1% experienced patient-initiated delays. There were no differences between hospital versus patient initiated delays by White vs non-White race (p=0.167). Eight percent of delays were due to a patient with known or suspected COVID-19. The median time from surgical consultation to proposed date of surgery was 20 days for both known malignancy and suspected malignancy, and 34.5 days for pre-invasive disease (p=0.005). Similarly, the median time from surgical consultation to actual date surgery was 23 days for patients with known or suspected malignancy compared to 64 days for preinvasive disease (p=0.011). Of eight patients undergoing treatment for ovarian cancer, 50% underwent primary debulking and 50% underwent neoadjuvant chemotherapy. Among all scheduled cases, the standard of care was met in 89.7% of cases. Standard of care treatment was achieved with a documented alternative plan in 6.1% of cases and with a non-surgical plan in 3% of cases. Download : Download high-res image (503KB) Download : Download full-size image Conclusions: During the ban on elective surgery in New York City during the first outbreak of the COVID-19 pandemic, many patients experienced minor surgical delays, but the majority of patients with known or suspected malignancies obtained appropriate, timely care. Ten percent of patients did not receive standard of care.

Objectives: An international consensus panel has defined locally advanced cervical cancers as a high priority malignancy during the COVID-19 pandemic and recommends prompt initiation of definitive treatment and completion of treatment (PMID 32563593). The objective of this study was to study the clinical outcomes of patients (pts) with cervical cancer treated with definitive chemoradiation (CRT) and brachytherapy (BT) at our institution in 2019 (pre-COVID) and in 2020 (peri-COVID). Methods: This was a retrospective cohort study of pts with FIGO Stage IB2-IVA cervical cancer at our institutions from 1/2019 to 10/2020. Pts received CRT followed by intracavitary brachytherapy (IC) with two operative insertions one week apart, or interstitial (IS) BT with one operative insertion. BT treatment was planned using image-guided CT or MR delineation. Pre-COVID was defined by initiation of CRT between 1/2019-12/2019, and peri-COVID was defined by initiation between 1/2020-10/2020. Process changes peri-COVID included limited on-site staff (e.g., minimal OR staff, no trainees, remote physics team), universal implementation of COVID-19 testing prior to surgery, and CT instead of MR-delineation based treatment. Outcomes of interest were time to treatment initiation and completion and differences in treatment planning modality or dosimetry. Fisher's exact and Mann Whitney U tests were used with significance p Results: Thirty pts were included, with 18 patients undergoing treatment pre-COVID and 12 peri-COVID. The median age at diagnosis pre-COVID was 57.7 (range 23-77) and for peri-COVID, 45.5 (range 28-62, p=0.06). There were no differences in non-English speaking pts (44% vs 59%, p=0.71) or uninsured pts (11% vs 33%, p=0.184) between the two cohorts. Median time to initiation of treatment from biopsy diagnosis was 52 days (range 13-209) in 2019 and for peri-COVID, 55.5 (range 20-173, p=0.71). During COVID, three pts had delayed initiation to treatment >100 days: two related to fertility and one due to fear of COVID-19. For this pt, tumor size progressed from 2.3cm to 4.2 cm maximal dimension. One pt treated in 2020 tested positive following treatment and did not require hospital admission. All pts completed CRT with RT: 24 pts pelvic RT (45 Gy), 3 pelvic and para-aortic RT (45 Gy with 57.5 Gy concomitant boost to nodes), 8 pts pelvic RT (45Gy) with sequential parametrial boost (50.4-59.4 Gy) using IMRT with no dose differences between pre and peri-COVID (Table 1). No pts required treatment breaks and the median overall treatment time was 50 days (range 31-85) in 2019 vs 50 days (range 43-63) in 2020 (p=0.710). Download : Download high-res image (105KB) Download : Download full-size image Conclusions: Despite the significant burden of the COVID-19 pandemic on our health care system, all cervical cancer pts receiving CRT met standard of care including CRT and BT within the recommended time frame with no significant differences in treatment parameters pre- and peri-COVID.

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.

Linusorbs (LOs) are natural peptides found in flaxseed oil that exert various biological activities. Of LOs, LOB3 ([1&ndash, 9-N&alpha, C]-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 &alpha, melanocyte-stimulating hormone (&alpha, 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.

Ethnopharmacological relevance Melicope accedens (Blume) Thomas G. Hartley is a plant included in the family Rutaceae and genus Melicope. It is a native plant from Vietnam that has been used for ethnopharmacology. In Indonesia and Malaysia, the leaves of M. accedens are applied externally to decrease fever. Aim of the study The molecular mechanisms of the anti-inflammatory properties of M. accedens are not yet understood. Therefore, we examined those mechanisms using a methanol extract of M. accedens (Ma-ME) and determined the target molecule in macrophages. Materials and methods We evaluated the anti-inflammatory effects of Ma-ME in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in an HCl/EtOH-triggered gastritis model in mice. To investigate the anti-inflammatory activity, we performed a nitric oxide (NO) production assay and ELISA assay for prostaglandin E2 (PGE2). RT-PCR, luciferase gene reporter assays, western blotting analyses, and a cellular thermal shift assay (CETSA) were conducted to identify the mechanism and target molecule of Ma-ME. The phytochemical composition of Ma-ME was analyzed by HPLC and LC-MS/MS. Results Ma-ME suppressed the production of NO and PGE2 and the mRNA expression of proinflammatory genes (iNOS, IL-1β, and COX-2) in LPS-stimulated RAW264.7 cells without cytotoxicity. Ma-ME inhibited NF-κB activation by suppressing signaling molecules such as IκBα, Akt, Src, and Syk. Moreover, the CETSA assay revealed that Ma-ME binds to Syk, the most upstream molecule in the NF-κB signal pathway. Oral administration of Ma-ME not only alleviated inflammatory lesions, but also reduced the gene expression of IL-1β and p-Syk in mice with HCl/EtOH-induced gastritis. HPLC and LC-MS/MS analyses confirmed that Ma-ME contains various anti-inflammatory flavonoids, including quercetin, daidzein, and nevadensin. Conclusions Ma-ME exhibited anti-inflammatory activities in vitro and in vivo by targeting Syk in the NF-κB signaling pathway. Therefore, we propose that Ma-ME could be used to treat inflammatory diseases such as gastritis.

Background Training helps maintain high-quality supervision and its associated benefits (e.g. reduced burnout, improved care). While studies have previously evaluated extended-duration supervision training programmes, none have treated these as complex interventions so have not employed realist approaches. Objectives Building on a previous realist synthesis, this evaluation tests and develops programme theory for extended-duration supervision training to answer the question: to what extent does the supervision training programme work, for whom, under what circumstances and why? Design We conducted a realist evaluation of a novel state-wide Victorian 3-month supervision training programme including one or two 3.5-h workshops followed by weekly reflexive longitudinal audio diaries (LADs) for up to 12 weeks. Methods Realist evaluation data comprised 25 entrance interviews with nurses and allied health professionals, 176 LADs (and 29 written diaries), and 23 exit interviews. We employed team-based realist analysis to identify context-mechanism-outcome configurations (CMOCs) to test and develop programme theory. Results We refined four recurring CMOCs from the realist synthesis programme theory, found insufficient evidence for two, and established five new recurring CMOCs. We identified multiple positive outcomes from our extended-duration supervision training programme (e.g. improved supervisor practices) through various mechanisms relating to pedagogy (e.g. weekly reflexivity), supervisors (e.g. engagement), and workplaces (e.g. enabling supervision cultures). Some negative outcomes were reported (e.g. decreased engagement) through various mechanisms (e.g. suboptimal training design). Such mechanisms were thought to come about by diverse contexts including supervisors (e.g. inexperienced/experienced), professions (nursing/allied health), and organisations (supervision-enabled/non-enabled cultures). Conclusions Our findings extend the realist synthesis programme theory by highlighting various contexts triggering outcome-generating mechanisms. Programme outcomes are maximised through ongoing supervisor reflexivity paying attention to facilitator-supervisor relationships, as well as protected time for supervisors to translate learning into practice.

Multiple myeloma is a hematologic malignancy characterized by presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. Multiple myeloma is diagnosed in an estimated 34 920 people in the US and in approximately 588 161 people worldwide each year.Among patients with multiple myeloma, approximately 73% have anemia, 79% have osteolytic bone disease, and 19% have acute kidney injury at the time of presentation. Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging. The Revised International Staging System combines data from the serum biomarkers β2 microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features found on fluorescence in situ hybridization-t(4;14), del(17p), and t(14;16)-to assess estimated progression-free survival and overall survival. At diagnosis, 28% of patients are classified as having Revised International Staging stage I multiple myeloma, and these patients have a median 5-year survival of 82%. Among all patients with multiple myeloma, standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor (ie, bortezomib), an oral immunomodulatory agent (ie, lenalidomide), and dexamethasone and is associated with median progression-free survival of 41 months, compared with historical reports of 8.5 months without therapy. This induction therapy combined with autologous hematopoietic stem cell transplantation followed by maintenance lenalidomide is standard of care for eligible patients.Approximately 34 920 people in the US and 155 688 people worldwide are diagnosed with multiple myeloma each year. Induction therapy with an injectable proteasome inhibitor, an oral immunomodulatory agent and dexamethasone followed by treatment with autologous hematopoietic stem cell transplantation, and maintenance therapy with lenalidomide are among the treatments considered standard care for eligible patients.

This is the author accepted manuscript. The final version is available from the Publisher via https://doi.org/10.1016/j.ejrad.2020.109182, BACKGROUND: Respiratory diseases are one of the leading causes of death worldwide, yet effective treatment options remain limited. Although inflammation is thought to be a key driver in the pathogenesis and progression of several lung diseases, the underlying molecular mechanisms of lung dysfunction remain poorly understood. Imaging techniques may help to further our understanding of the pathophysiology and facilitate the translation of novel therapies. Positron Emission Tomography (PET) is a functional imaging technique which has the potential to interrogate the underlying inflammatory response. We present a systematic review of the literature summarising the emerging PET radiotracers developed to quantify pulmonary inflammation. METHOD: We performed a systematic review using the following databases: Medline, Embase, Scopus, PubMed, Web of Science and Cochrane. We included articles between 1995 and 2019 for all studies using PET radiotracers to evaluate inflammatory response in the lung. From a total of 911 articles covering both animal and human studies, two reviewers selected papers based on the inclusion/exclusion criteria and extracted data from 68 articles selected. RESULTS: 53 out of 68 papers, including both human and animal studies, were eligible for synthesis. Heterogenous study populations and differences in study design, image acquisition and analysis made data pooling unfeasible; instead, we provide a narrative synthesis. CONCLUSIONS: Currently, very few novel radiotracers targeting lung inflammation have crossed the translational gap from animal models to human studies. Nevertheless, our results highlight a handful of promising tracers which warrant further evaluation in humans. 18F-FDG has been investigated most extensively; although 18F-FDG is not a specific inflammatory tracer, human studies of several pulmonary diseases support its use as a biomarker for inflammation. Despite ongoing debate about the optimal analysis methodology for 18F-FDG lung images, standardisation of image acquisition and analysis should help to improve confidence in research outcomes. PET radiotracers can provide quantitative, targeted biomarkers which relate to the activity of molecular pathways and may expedite development of specific anti-inflammatory drugs.

Highlights • Vaginal masses after hysterectomy for benign indications should be investigated. • Opportunistic salpingectomies may decrease incidence of epithelial ovarian cancers. • Consider regular pelvic exams for women with asymptomatic prolapsed fallopian tubes., 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.

Background The prevalence of cancer among children with stroke is unknown. This study sought to evaluate cancer- and tumor-associated childhood ischemic stroke in a multinational pediatric stroke registry. Methods Children aged 29 days to less than 19 years with arterial ischemic stroke or cerebral sinovenous thrombosis enrolled in the International Pediatric Stroke Study between January 2003 and June 2019 were included. Data including stroke treatment and recurrence were compared between subjects with and without cancer using Wilcoxon rank sum and chi-square tests. Results Cancer or tumor was present in 99 of 2968 children (3.3%) with arterial ischemic stroke and 64 of 596 children (10.7%) with cerebral sinovenous thrombosis. Among children in whom cancer type was identified, 42 of 88 arterial ischemic stroke cases (48%) had brain tumors and 35 (40%) had hematologic malignancies; 45 of 58 cerebral sinovenous thrombosis cases (78%) had hematologic malignancies and eight (14%) had brain tumors. Of 54 cancer-associated arterial ischemic stroke cases with a known cause, 34 (63%) were due to arteriopathy and nine (17%) were due to cardioembolism. Of 46 cancer-associated cerebral sinovenous thrombosis cases with a known cause, 41 (89%) were related to chemotherapy-induced or other prothrombotic states. Children with cancer were less likely than children without cancer to receive antithrombotic therapy for arterial ischemic stroke (58% vs 80%, P = 0.007) and anticoagulation for cerebral sinovenous thrombosis (71% vs 87%, P = 0.046). Recurrent arterial ischemic stroke (5% vs 2%, P = 0.04) and cerebral sinovenous thrombosis (5% vs 1%, P = 0.006) were more common among children with cancer. Conclusions Cancer is an important risk factor for incident and recurrent childhood stroke. Stroke prevention strategies for children with cancer are needed.

Background Nursing leadership plays a vital role in shaping outcomes for healthcare organizations, personnel and patients. With much of the leadership workforce set to retire in the near future, identifying factors that positively contribute to the development of leadership in nurses is of utmost importance. Objectives To identify determining factors of nursing leadership, and the effectiveness of interventions to enhance leadership in nurses. Design We conducted a systematic review, including a total of nine electronic databases. Data Sources Databases included: Medline, Academic Search Premier, Embase, PsychInfo, Sociological Abstracts, ABI, CINAHL, ERIC, and Cochrane. Review Methods Studies were included if they quantitatively examined factors contributing to nursing leadership or educational interventions implemented with the intention of developing leadership practices in nurses. Two research team members independently reviewed each article to determine inclusion. All included studies underwent quality assessment, data extraction and content analysis. Results 49,502 titles/abstracts were screened resulting in 100 included manuscripts reporting on 93 studies (n=44 correlational studies and n=49 intervention studies). One hundred and five factors examined in correlational studies were categorized into 5 groups experience and education, individuals’ traits and characteristics, relationship with work, role in the practice setting, and organizational context. Correlational studies revealed mixed results with some studies finding positive correlations and other non-significant relationships with leadership. Participation in leadership interventions had a positive impact on the development of a variety of leadership styles in 44 of 49 intervention studies, with relational leadership styles being the most common target of interventions. Conclusions The findings of this review make it clear that targeted educational interventions are an effective method of leadership development in nurses. However, due to equivocal results reported in many included studies and heterogeneity of leadership measurement tools, few conclusions can be drawn regarding which specific nurse characteristics and organizational factors most effectively contribute to the development of nursing leadership. Contextual and confounding factors that may mediate the relationships between nursing characteristics, development of leadership and enhancement of leadership development programs also require further examination. Targeted development of nursing leadership will help ensure that nurses of the future are well equipped to tackle the challenges of a burdened health-care system.

Background and Purpose— The recent Save ChildS study provides multicenter evidence for the use of mechanical thrombectomy in children with large vessel occlusion arterial ischemic stroke. However, device selection for thrombectomy may influence rates of recanalization, complications, and neurological outcomes, especially in pediatric patients of different ages. We, therefore, performed additional analyses of the Save ChildS data to investigate a possible association of different thrombectomy techniques and devices with angiographic and clinical outcome parameters. Methods— The Save ChildS cohort study (January 2000–December 2018) analyzed data from 27 European and United States stroke centers and included all pediatric patients ( Results— Seventy-three patients with a median age of 11.3 years were included. Currently available stent retrievers were used in 59 patients (80.8%), of which 4×20 mm (width×length) was the most frequently chosen size (36 patients =61%). A first-line ADAPT approach was used in 7 patients (9.6%), and 7 patients (9.6%) were treated with first-generation thrombectomy devices. In this study, a first-line ADAPT approach was neither associated with the rate of successful recanalization (ADAPT 85.7% versus 87.5% No ADAPT) nor with the complication rate or the neurological outcome. Moreover, there were no associations of stent retriever sizes with rates of recanalization, complication rates, or outcome parameters. Conclusions— Our study suggests that neurological outcomes are generally good regardless of any specific device selection and suggests that it is important to offer thrombectomy in eligible children regardless of technique or device selection. Registration— URL: https://www.drks.de/ ; Unique identifier: DRKS00016528.

Exacerbations of chronic obstructive pulmonary disease (COPD) are currently diagnosed based on changes in respiratory symptoms. Characterizing the imaging manifestation of exacerbations could be useful for objective diagnosis of exacerbations in the clinic and clinical trials, as well as provide a mechanism for monitoring exacerbation treatment and recovery. In this systematic review, we employed a comprehensive search across three databases (Medline, EMBASE, Web of Science) to identify studies that performed imaging of the thorax at COPD exacerbation. We included 51 from a total of 5,047 articles which met all our inclusion criteria. We used an adapted version of the Modified Newcastle-Ottawa Quality Assessment Scale for cohort studies to assess the quality of the included studies. Conclusions were weighted towards higher-quality articles. We identified a total of 36 thoracic imaging features studied at exacerbation of COPD. Studies were generally heterogeneous in their measurements and focus. Nevertheless, considering studies which performed consecutive imaging at stable state and exacerbation, which scored highest for quality, we identified salient imaging biomarkers of exacerbations. An exacerbation is characterized by airway wall and airway calibre changes, hyperinflation, pulmonary vasoconstriction and imaging features suggestive of pulmonary arterial hypertension. Most information was gained from CT studies. We present the first ever composite imaging signature of COPD exacerbations. While imaging during an exacerbation is comparatively new and not comprehensively studied, it may uncover important insights into the acute pathophysiologic changes in the cardiorespiratory system during exacerbations of COPD, providing objective confirmation of events and a biomarker of recovery and treatment response.

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.

There is a paucity of data regarding outcomes and response to standard therapy in patients with limited-stage (LS) agressive B-cell lymphoma (LS-ABCL) who harbor MYC rearrangement (MYC-R) with or without BCL2 and/or BCL6 rearrangements. We conducted a multicenter retrospective study of MYC-R LS-ABCL patients who received either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or more intensive immunochemotherapy (IIC) plus or minus consolidative involved-field radiation therapy (IFRT). One hundred four patients from 15 academic centers were included. Forty four patients (42%) received R-CHOP, of whom 52% had IFRT. Sixty patients (58%) received IIC, of whom 40% had IFRT. Overall response rate was 91% (84% complete response [CR]; 7% partial response). Patients with double-hit lymphoma (DHL; n = 40) had a lower CR rate compared with patients with MYC-R only (75% vs 98%; P = .003). CR rate was higher in the IFRT vs no-IFRT group (98% vs 72%; P < .001). Median follow-up was 3.2 years; 2-year progression-free survival (PFS) and overal survival (OS) were 78% and 86% for the entire cohort, and 74% and 81% for the DHL patients, respectively. PFS and OS were similar across treatment groups (IFRT vs no IFRT, R-CHOP vs IIC) in the entire cohort and in DHL patients. Our data provide a historical benchmark for MYC-R LS-ABCL and LS-DHL patients and show that outcomes for this population may be better than previously recognized. There was no benefit of using IIC over R-CHOP in patients with MYC-R LS-ABCL and LS-DHL.

Murine models have become powerful tools in leukemia research for investigating interactions between blast cells niche factors. In the tumor microenvironment, immune cells are one of the most important niche factors, capable of mounting dynamic innate or adoptive responses against leukemic cells. Acute myeloid leukemia (AML) is a systemic cancer accompanied by immune disruption. In order to exploit the enhanced activity of immune cells in AML treatment, the use of syngeneic mouse models is necessary. Studies of crosstalk between cancer blast cells and immune cells in syngeneic mouse models are beneficial, as the absence of immune functions in syngeneic models enables focus on cancer-associated immune reactions. Once AML is induced, innate and adoptive immune cells respond differently, ultimately resulting in suppression of the immune cells. Murine AML models are commonly induced by intravenous or subcutaneous injection of C1498 cells. Despite the popularity of murine models, they have not yet resulted in the elucidation of distinct differences in immune cells by the injection method. Here, we investigated the frequency of immune cells and survival rate of mice with AML induced using both injection methods.

Importance Randomized clinical trials have shown the efficacy of thrombectomy of large intracranial vessel occlusions in adults; however, any association of therapy with clinical outcomes in children is unknown. Objective To evaluate the use of endovascular recanalization in pediatric patients with arterial ischemic stroke. Design, Setting, and Participants This retrospective, multicenter cohort study, conducted from January 1, 2000, to December 31, 2018, analyzed the databases from 27 stroke centers in Europe and the United States. Included were all pediatric patients ( Exposures Endovascular recanalization. Main Outcomes and Measures The decrease of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score from admission to day 7 was the primary outcome (score range: 0 [no deficit] to 34 [maximum deficit]). Secondary clinical outcomes included the modified Rankin scale (mRS) (score range: 0 [no deficit] to 6 [death]) at 6 and 24 months and rate of complications. Results Seventy-three children from 27 participating stroke centers were included. Median age was 11.3 years (interquartile range [IQR], 7.0-15.0); 37 patients (51%) were boys, and 36 patients (49%) were girls. Sixty-three children (86%) received treatment for anterior circulation occlusion and 10 patients (14%) received treatment for posterior circulation occlusion; 16 patients (22%) received concomitant intravenous thrombolysis. Neurologic outcome improved from a median PedNIHSS score of 14.0 (IQR, 9.2-20.0) at admission to 4.0 (IQR, 2.0-7.3) at day 7. Median mRS score was 1.0 (IQR, 0-1.6) at 6 months and 1.0 (IQR, 0-1.0) at 24 months. One patient (1%) developed a postinterventional bleeding complication and 4 patients (5%) developed transient peri-interventional vasospasm. The proportion of symptomatic intracerebral hemorrhage events in the HERMES meta-analysis of trials with adults was 2.79 (95% CI, 0.42-6.66) and in Save ChildS was 1.37 (95% CI, 0.03-7.40). Conclusions and Relevance The results of this study suggest that the safety profile of thrombectomy in childhood stroke does not differ from the safety profile in randomized clinical trials for adults; most of the treated children had favorable neurologic outcomes. This study may support clinicians’ practice of off-label thrombectomy in childhood stroke in the absence of high-level evidence.

Murine models have become powerful tools in leukemia research for investigating interactions between blast cells niche factors. In the tumor microenvironment, immune cells are one of the most important niche factors, capable of mounting dynamic innate or adoptive responses against leukemic cells. Acute myeloid leukemia (AML) is a systemic cancer accompanied by immune disruption. In order to exploit the enhanced activity of immune cells in AML treatment, the use of syngeneic mouse models is necessary. Studies of crosstalk between cancer blast cells and immune cells in syngeneic mouse models are beneficial, as the absence of immune functions in syngeneic models enables focus on cancer-associated immune reactions. Once AML is induced, innate and adoptive immune cells respond differently, ultimately resulting in suppression of the immune cells. Murine AML models are commonly induced by intravenous or subcutaneous injection of C1498 cells. Despite the popularity of murine models, they have not yet resulted in the elucidation of distinct differences in immune cells by the injection method. Here, we investigated the frequency of immune cells and survival rate of mice with AML induced using both injection methods.

Endocrine disrupting chemicals (EDCs) disrupt the physiological metabolism, thus playing an important role in the development of obesity. EDCs, the so-called &lsquo, obesogens&rsquo, 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 &plusmn, 0.57 mg gallic acid equivalents (GAE)/g and 57.31 &plusmn, 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-&gamma, C/EBP-&alpha, 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.

Background and Purpose— Data regarding the safety and efficacy of intravenous tPA (tissue-type plasminogen activator) in childhood acute arterial ischemic stroke are inadequate. The TIPS trial (Thrombolysis in Pediatric Stroke; National Institutes of Health grant R01NS065848)—a prospective safety and dose-finding trial of intravenous tPA in acute childhood stroke—was closed for lack of accrual. TIPS sites have subsequently treated children with acute stroke in accordance with established institutional protocols supporting data collection on outcomes. Methods— Data on children treated with intravenous tPA for neuroimaging-confirmed arterial ischemic stroke were collected retrospectively from 16 former TIPS sites to establish preliminary safety data. Participating sites were required to report all children who were treated with intravenous tPA to minimize reporting bias. Symptomatic intracranial hemorrhage (SICH) was defined as ECASS (European Cooperative Acute Stroke Study) II parenchymal hematoma type 2 or any intracranial hemorrhage associated with neurological deterioration within 36 following tPA administration. A Bayesian beta-binomial model for risk of SICH following intravenous tPA was fit using a prior distribution based on the risk level in young adults (1.7%); to test for robustness, the model was also fit with uninformative and conservative priors. Results— Twenty-six children (age range, 1.1–17 years; median, 14 years; 12 boys) with stroke and a median pediatric National Institutes of Health Stroke Scale score of 14 were treated with intravenous tPA within 2 to 4.5 hours (median, 3.0 hours) after stroke onset. No patient had SICH. Two children developed epistaxis. Conclusions— The estimated risk of SICH after tPA in children is 2.1% (95% highest posterior density interval, 0.0%–6.7%; mode, 0.9%). Regardless of prior assumption, there is at least a 98% chance that the risk is