bluuebunny/crossref_metadata_2025 huggingface dataset:
Discharge against medical advice among neurological patients: Characteristics and outcomes
Authors: Raja Aishwarya , Trivedi Parth D. , Dhamoon Mandip S.
Published: June 2020

Objective

To study characteristics and outcomes of patients with stroke, traumatic brain injury (TBI), and epilepsy with discharge against medical advice (DAMA).

Data Sources/Study Setting

Retrospective analysis of the 2013 Nationwide Readmissions Database, a nationally representative inpatient administrative dataset.

Study Design

Associations between predictors and DAMA at index admission were analyzed using adjusted logistic models. We examined 30‐day all‐cause readmissions.

Data Collection Methods

Patients aged ≥18 years at index admission for International Classification of Diseases‐9 diagnosis code of epilepsy, TBI, or stroke were included.

Principal Findings

Discharge against medical advice occurred in 1998/58278 patients (3.43 percent) in the epilepsy group, 1762/211 213 (0.83 percent) in the stroke group, and 1289/74 652 (1.73 percent) in the TBI group. Factors consistently associated with increased likelihood of DAMA included lower age, male sex, non‐Medicare and nonprivate insurance, lower socioeconomic status, and behavioral risk factors (smoking history, alcohol history, and drug use). The crude 30‐day all‐cause readmission rate for those with DAMA from their index admission was 16.4 percent for the stroke cohort, 13.9 percent for epilepsy, and 13.4 percent for TBI. DAMA at index admission was significantly associated with increased risk of 30‐day all‐cause readmission among all groups (adjusted odds ratio 1.79, 95% CI: 1.65‐1.94, P < .0001).

Conclusions

Age, sex, insurance status, socioeconomic status, and behavioral factors were associated with DAMA in neurological patients. Further research is needed to develop interventions to reduce DAMA in high‐risk groups.
What proportion of healthcare worker masks carry virus? A systematic review
Authors: Jones Peter , Roberts Sally , Hotu Cheri , Kamona Sinan
Published: June 2020

Objective

Concerns have been raised by healthcare organisations in New Zealand that routine mask use by healthcare workers (HCW) may increase the risk of transmission of SARS‐CoV‐2 through increased face touching. Routine mask use by frontline HCW was not recommended when seeing ‘low risk’ patients. The aim of this review was to determine the carriage of respiratory viruses on facemasks used by HCW.

Methods

A systematic review was conducted with structured searches of medical and allied health databases. Two authors independently screened articles for inclusion, with substantial agreement (k = 0.66, 95% CI 0.54–0.79). Studies that at least one author recommended for full text review were reviewed in full for inclusion. Two authors independently extracted data from included studies including the setting, method of analysis and results. There was exact agreement on the proportion of virus detected on masks.

Results

We retrieved 1233 titles, 47 underwent full text review and five studies reported in four articles were included. The studies were limited by small numbers and failure to test all eligible masks in some studies. The proportion in each study ranged from 0 (95% CI 0–10) to 25% (95% CI 8–54). No study reported clinical respiratory illness as a result of virus on the masks.

Conclusions

Although limited, current evidence suggests that viral carriage on the outer surface of surgical masks worn by HCW treating patients with clinical respiratory illness is low and there was not strong evidence to support the assumption that mask use may increase the risk of viral transmission.
Prediction of peak occurrence of Dendrolimus punctatus larvae based on Bayes discriminant method
Authors: Qian Guangjing , Song Xueyu , Sun Jiazhao , Zhang Shuping , Zhou Xiazhi , Zhang Guoqing , Zou Yunding , Fang Guofei , Zhang Zhen , Yan Ping , Bi Shoudong
Published: June 2020

To improve the accuracy of forecasting the peak occurrence of Dendrolimus punctatus Walker, we here used the Bayes discriminant analysis to predict this peak occurrence for the first and second generation of Dendrolimus punctatus larvae based on these data from 1983 to 2016 in Qianshan County, Anhui Province. Our present results showed that this discriminant equation for the first generation was as follows: f(1) = −3.2588‐6.2700x1 + 1.2870x2 + 0.7920x3 + 0.4152x4; f(2) = −14.5215‐8.5710x1 + 2.9790x2 + 2.0280x3 + 0.5031x4; f(3) = −3.5264; f(4) = −66.8312‐12.5216x1 + 5.1740x2 + 4.7162x3 + 0.6033x4. And that the prediction accuracy for the first generation was 97.22%. Whilst this discriminant equation for the second generation was as follows: f(1) = −3.536‐1.192x5 + 1.338x6 + 0.638x7−0.025x8; f(2) = −7.317‐1.337x5 + 4.240x6 + 1.010x7−0.295x8; f(3) = −16.488‐3.192x5 + 4.955x6 + 1.900x7–0.411x8; f(4) = −34.502‐4.184x5 + 7.484x6 + 2.583x7–0.443x8. The prediction accuracy for the second generation was 85.71%. Overall, our findings revealed that the Bayes discriminant analysis could screen out key factors to significantly improve the prediction accuracy of peak occurrence of Dendrolimus punctatus larvae.
Effects of deodorization temperature and time on the formation of 3‐MCPD, 2‐MCPD, and glycidyl esters and physicochemical changes of palm oil
Authors: Tivanello Renan , Capristo Maisa , Vicente Eduardo , Ferrari Roseli , Sampaio Klicia , Arisseto Adriana
Published: June 2020

This study verified the formation profile of esters of 3‐monochloropropane‐1,2‐diol (3‐MCPDE), 2‐monochloropropane‐1,2‐diol (2‐MCPDE), and glycidol (GE), and evaluated the physicochemical changes (free‐fatty acid, acylglycerols, and colour) that occurred during the deodorization of palm oil in different conditions of time (30, 60, 90, and 120 min) and temperature (210, 230, 250, and 270 °C). Levels of 3‐MCPD and 2‐MCPD esters ranged from 1.91 to 2.70 mg/kg and 0.68 to 1.44 mg/kg, respectively, and were formed at the mildest tested condition (210 °C, 30 min). No correlation was observed between these contaminants and physicochemical changes. GE levels varied from 0.12 to 8.51 mg/kg and showed correlation with color and diacylglycerol content. While the temperature had little influence on the formation of esters of 3‐MCPD and 2‐MCPD, the content of GE considerably raised above 250 °C.
Protective effect of seabuckthorn berry juice against acrylamide‐induced oxidative damage in rats
Authors: Zhao Sijia , Sun Hongyang , Liu Qingbo , Shen Yu , Jiang Yujun , Li Yanhua , Liu Tong , Liu Tianxu , Xu Honghua , Shao Meili
Published: June 2020

Acrylamide (AA), classified as a probable carcinogen, can be neurotoxic, genotoxic, and can damage DNA. This study explored the ability of seabuckthorn berries juice (SBJ) to alleviate AA‐induced toxic injury in rats. Twenty‐four adult male Sprague‐Dawley (SD) rats were randomly divided into four groups: control group, AA group (40 mg/kg), AA + SBJ (40 mg/kg AA and 5 mL/kg SBJ), and AA + vitamin C (VC) group (positive control group, 40 mg/kg AA and 100 mg/kg VC). At the end of the experiment, rats in AA group showed a marked decrease in the rate of weight gain, hind extremity abduction, and ataxia. Obvious anomalies were seen in plasma biochemical parameters (P < 0.05), and different degrees of injury were observed upon histological examination of five tissues (hippocampus, cerebellum, liver, small intestine, and kidney). Compared to the control group, levels of superoxide dismutase, catalase, and glutathione were significantly decreased, while malondialdehyde was elevated (P < 0.05). SBJ treatment reduced the abnormal of behavior, hematological index, antioxidant enzyme, and tissue damage caused by AA in rats.

Practical Application

Seabuckthorn berries are wild berries rich in vitamin C and polyphenols, which have good antioxidant properties. In this experiment, SBJ has a significant alleviating effect on AA‐induced oxidative damage in rats. Therefore, we speculate that SBJ may relieve the oxidative damage caused by diet or other forms of AA exposure in the general population. At the same time, this experiment also provides new ideas for alleviating AA‐induced in vivo toxicity.
Encapsulation of wheat germ oil in alginate‐gelatinized corn starch beads: Physicochemical properties and tocopherols’ stability
Authors: Feltre Gabriela , Sartori Tanara , Silva Klycia F. C. , Dacanal Gustavo C. , Menegalli Florencia C. , Hubinger Miriam D.
Published: June 2020

Microencapsulation by production of polymer beads from ionic gelation is a useful method to improve the stability of nutritional compounds. Wheat germ oil is a nutritional source of unsaturated fatty acids and phytonutrients, such as tocopherols (α and β), phytosterols, carotenoids, and phenolic compounds. This work studied the development of alginate‐starch beads over the stability of encapsulated wheat germ oil. The beads contained sodium alginate and gelatinized corn starch in proportions of 2:0, 1:1, 1:2, and 1:4. The addition of small amounts (1:1) of gelatinized starch in the alginate emulsions improved the physicochemical properties and stability during storage. The emulsions had oil droplets with mean sizes ranging from 4.5 to 12.2 µm. The 1:1 samples showed more disperse oil droplets, explained by the molecular interaction between the starch chains and oil. The encapsulation efficiency was higher than 91%, and the beads’ mean diameters were between 383.22 and 797.45 µm. The proportion of 1:1 alginate‐starch also enhanced the beads’ microstructures, avoiding oil oxidation. Six days accelerated stability (65 °C) evidenced higher tocopherols amounts (0.66 mg/g oil) and a lower oxidation (2.52 meq.O2/kg oil) for the 1:1 samples compared to the remained samples.

Practical Application

Alginate‐gelatinized corn starch beads loaded with wheat germ oil can be used as an ingredient in functional food products for the enrichment of nutrients. The use of starch decreased the oil oxidation and the loss of tocopherols during storage, indicating that the quality of the wheat germ oil will be desirable for longer durations of food storage.
Efficacy and safety of endoscopic submucosal tunnel dissection vs endoscopic submucosal dissection for early superficial upper gastrointestinal precancerous lesions and tumors: A meta‐analysis
Authors: Liu Yu Zhi , Lv Xiu He , Deng Kai , Yang Jin Lin
Published: June 2020

Objective

Endoscopic submucosal tunnel dissection (ESTD) is a new treatment for superficial upper gastrointestinal precancerous lesions and tumors. However, its safety and efficacy for treating these lesions is still uncertain. This meta‐analysis aimed to compare the efficacy and safety of ESTD with those of endoscopic submucosal dissection (ESD) in treating early superficial upper gastrointestinal precancerous lesions and tumors.

Methods

Electronic databases, including EMBASE, PubMed, Cochrane Library and the Web of Science, were systematically searched for articles published up to 1 April 2020. The primary outcomes were complete and en bloc resection rates of the lesions. The secondary outcomes included operation time, speed of dissection, complication and recurrence rates. The Newcastle‐Ottawa quality assessment scale was used to evaluate the quality of the studies.

Results

Seven studies were included in the final meta‐analysis. The complete and en bloc resection rates of early superficial esophageal lesions as well as the en bloc resection rate of early superficial gastric lesions were similar between the ESTD and ESD groups. Compared with the ESD group, the ESTD group had a higher en bloc resection rate for early superficial gastric lesions. A faster dissection speed was observed in both superficial esophageal and gastric lesions. In gastric lesions, the operation time of the ESTD group was shorter than that of the ESD group, while it did not differ for esophageal lesions. There were no obvious differences in bleeding and perforation rates between the groups.

Conclusion

As an endoscopic technique for treating early superficial upper gastrointestinal lesions, ESTD is as safe as and more effective than ESD, especially for gastric lesions.
Proteomic characterization of extracellular vesicles produced by several wine yeast species
Authors: Mencher Ana , Morales Pilar , Valero Eva , Tronchoni Jordi , Patil Kiran Raosaheb , Gonzalez Ramon
Published: June 2020

In winemaking, the use of alternative yeast starters is becoming increasingly popular. They contribute to the diversity and complexity of wine sensory features and are typically used in combination with Saccharomyces cerevisiae, to ensure complete fermentation. This practice has drawn the interest on interactions between different oenological yeasts, which are also relevant in spontaneous and conventional fermentations, or in the vineyard. Although several interactions have been described and some mechanisms have been suggested, the possible involvement of extracellular vesicles (EVs) has not yet been considered. This work describes the production of EVs by six wine yeast species (S. cerevisiae, Torulaspora delbrueckii, Lachancea thermotolerans, Hanseniaspora uvarum, Candida sake and Metschnikowia pulcherrima) in synthetic grape must. Proteomic analysis of EV‐enriched fractions from S. cerevisiae and T. delbrueckii showed enrichment in glycolytic enzymes and cell‐wall‐related proteins. The most abundant protein found in S. cerevisiae, T. delbrueckii and L. thermotolerans EV‐enriched fractions was the enzyme exo‐1,3‐β‐glucanase. However, this protein was not involved in the here‐observed negative impact of T. delbrueckii extracellular fractions on the growth of other yeast species. These findings suggest that EVs may play a role in fungal interactions during wine fermentation and other aspects of wine yeast biology.
Hassling: How States Prevent a Preventive War
Authors: Schram Peter
Published: June 2020

Low‐level military operations outside of war are pervasive in the international system. These activities have been viewed as destabilizing by both academics and policy makers, as miscalculations or missteps in conducting low‐level operations can risk escalation to war. I show the opposite can be true: these operations can prevent escalation to a greater war. I examine a type of low‐level conflict that I call “hassling” in the common framework of bargaining and war. The critical feature of hassling is that it weakens a targeted state. I find that when a rising power rules out peaceful bargains, hassling the rising power can prevent a preventive war, with efficiency gains for the involved states. This intuition is formalized in a dynamic model of conflict and is explored through examinations of Israel's Operation Outside the Box (2007), the United States' involvement in Iraq (1991–2003), and Russia's operations in Ukraine (beginning in 2014).
Impaired airway epithelial cell wound‐healing capacity is associated with airway remodelling following RSV infection in severe preschool wheeze
Authors: Andersson Cecilia K. , Iwasaki Jua , Cook James , Robinson Polly , Nagakumar Prasad , Mogren Sofia , Fleming Louise , Bush Andrew , Saglani Sejal , Lloyd Clare M.
Published: June 2020

Background

Respiratory syncytial virus (RSV) causes exacerbations of asthma and preschool wheeze (PSW). However, the anti‐viral and repair responses of the bronchial epithelium in children with severe therapy‐resistant asthma (STRA) and PSW are poorly understood.

Methods

Children with STRA (age 12 [6‐16] years), PSW (age 2 [1‐5] years) and non‐asthmatic controls (age 7 [2‐14] years) underwent bronchoscopy with endobronchial brushings and biopsies. Anti‐viral, wound injury responses were quantified in biopsies and primary bronchial epithelial cells (PBECs) in response to RSV, poly(I:C), house dust mite (HDM) or IL‐33 using RT‐qPCR, Luminex and live cell imaging. Collagen deposition and tissue expression of epithelial growth factor receptor (EGFR), IL‐33 and receptor ST2 were investigated in bronchial biopsies.

Results

PBECs from STRA and PSW had increased TLR3 gene expression and increased secretion of anti‐viral and pro‐inflammatory cytokines (IFN‐γ, IL‐6 and IL‐13) in response to RSV compared to controls. Exposure of PBECs to concomitant TLR3 agonist poly(I:C) and HDM resulted in a significant reduction in epithelial cell proliferation in PSW compared to controls. Wound‐healing was also impaired in PSW compared to controls at baseline and following IL‐33 stimulation. In addition, tissue EGFR expression was significantly reduced in PSW and correlated with collagen deposition in endobronchial biopsies.

Conclusions

Despite increased anti‐viral responses, preschool children with severe wheeze had impaired airway epithelial proliferative responses following damage. This might be connected to the low expression of EGFR in PSW which may affect epithelial function and contribute to asthma pathogenesis.
Characteristics of penile growth in pubertal rats and a non‐invasive method to lengthen the penis
Authors: Li Tao , Fu Fudong , Wu Changjing , Qin Feng , Yuan Jiuhong
Published: June 2020

Background

Males with short penises may suffer from sexual dysfunction and psychological problems. However, currently, managing short penis is a huge challenge.

Objectives

To explore whether inhibition of lysyl oxidase (LOX) activity (anti‐LOX) combined with a vacuum device could lengthen the penis of pubertal rat.

Materials and Methods

Male rats of different ages were purchased, their exposed penile lengths and weights were measured, and protein expression and lysyl oxidase activity in the corpus cavernosum were analyzed. Fifteen‐day‐old rats were then purchased and divided into six groups: control, Anti‐lysyl oxidase, −200 mm Hg (vacuum device under −200 mm Hg value), −200 mm Hg + Anti‐lysyl oxidase, −300 mm Hg, and −300 mm Hg + Anti‐lysyl oxidase groups. After the intervention duration of 7 weeks, rats' penile length was measured and erectile function was assessed. The corpus cavernosum was harvested for histopathology and molecular assessments.

Results

Exposed penile length and weight significantly increased with age, especially between 4 and 8 weeks. Both the protein expression and lysyl oxidase activity in corpus cavernosum were the highest at 2 weeks; however, they quickly decreased with age and slowly declined after 8 weeks. Anti‐lysyl oxidase significantly increased the penile length by 10.79% over controlled rats, −200 mm Hg + Anti‐lysyl oxidase lengthened it by 14.05%, and −300 mm Hg + Anti‐lysyl oxidase increased it by 19.84%. Anti‐lysyl oxidase significantly reduced lysyl oxidase activity to decrease pyridinoline concentration; however, it did not change desmosine (P = .28), hydroxyproline (P = .14), and total elastin (P = .06) levels. Anti‐lysyl oxidase with or without a vacuum device did not diminish erectile function or impair the normal microstructure of corpus cavernosum.

Discussion and Conclusion

The rats' penile growth peaks occurred between 4 and 8 weeks. Anti‐lysyl oxidase with a vacuum device promoted penile lengthening by inhibiting pyridinoline production to induce tunica albuginea remodeling. The penile lengthening effect was more obvious in pubertal rats than the adult rats. None of the procedures decreased erectile function.
Scoping review of head and neck neoplasms presenting with obstructive sleep apnoea: the importance of flexible nasendoscopy
Authors: Moore Phillip , Cardemil Felipe , Hayward Nathan J. , Flatman Samuel
Published: June 2020

Background

Obstructive sleep apnoea (OSA) can be caused by neoplasms involving the upper aerodigestive tract. Currently, many of these patients have this diagnosis missed, as most adults diagnosed with OSA do not undergo adequate head and neck examination including flexible nasendoscopy. We performed a review of the literature to shed light on this phenomenon and outline the pathologies and issues surrounding this sub‐population of patients diagnosed with OSA.

Methods

A scoping review of the literature was conducted on head and neck neoplasms presenting with OSA. Data were extracted on demographics, clinical presentation, histopathology, treatment and patient outcomes.

Results

Sixty‐seven articles were included, describing 79 patients. Mean age was 45.8 years, and 77.2% were male. Symptoms of OSA were present for an average of 29.2 months before a diagnosis of causative neoplasm was made. Forty‐two different benign and malignant histopathological entities were reported. At diagnosis, the causative pathology of 100% of patients was visible on head and neck examination including flexible nasendoscopy, while only 53.2% were visible on trans‐oral examination. One‐third of patients had commenced inappropriate treatment for OSA, including three who had undergone sleep surgical procedures. The majority of patients were treated with surgery alone (72.2%).

Conclusion

Although rare, neoplasms of the upper aerodigestive tract should be considered as a cause of OSA, especially in patients experiencing other symptoms in addition to the typical symptoms of OSA. They should particularly be considered in patients with comparatively lower body mass index or those with worsening OSA without an apparent cause identified.
Analysis of differential strategies to enhance detection of low‐abundance proteins in the bovine serum proteome
Authors: Schalich Kasey M. , Herren Anthony W. , Selvaraj Vimal
Published: June 2020

Serum‐based biomarkers hold propitious applications for addressing livestock health, and management. However, discovery of protein biomarkers in complex biological fluids like serum is wholly intractable due to the large dynamic range of protein concentrations; that is, ˜10–12 high abundance proteins constitute >90% of the total protein content and effectively mask proteomic detection of low‐abundance biomarkers. Toward addressing this limitation, we test a continuous elution size‐based fractionation method, and two approaches that use affinity interaction‐based separation of proteins in preparing bovine serum, and compare liquid chromatography tandem mass spectrometry protein identification to neat serum. Our results identify the high‐abundance proteins in bovine serum, and demonstrate dynamic range compression and improved protein identification with the different enrichment methods. Although these findings indicate the highest protein number identified in bovine serum (445 proteins, all methods combined), and by any single sample processing method (312 proteins) to date, they still remain lower than levels deemed necessary for biomarker discovery. As such, this investigation revealed limitations to resolving the bovine serum proteome, and the need for species‐specific tools for immunodepleting high‐abundance proteins. In concert, this study represents a step toward advancing sample preparation methods for bovine serum biomarker identification.
In chronic lymphocytic leukaemia, SLAMF1 deregulation is associated with genomic complexity and independently predicts a worse outcome
Authors: Rigolin Gian Matteo , Saccenti Elena , Melandri Aurora , Cavallari Maurizio , Urso Antonio , Rotondo Francesco , Betulla Anita , Tognolo Lucia , Bardi Maria Antonella , Rossini Marika , Tammiso Elisa , Bassi Christian , Cavazzini Francesco , Negrini Massimo , Cuneo Antonio
Published: June 2020

In a series of 349 patients with chronic lymphocytic leukaemia (CLL), we found lower levels of signalling lymphocytic activation molecule family member 1 (SLAMF1) expression in cases with highly complex karyotypes, as defined by the presence of five or more chromosomal abnormalities (CK5; P < 0·001) and with major chromosomal structural abnormalities (P < 0·001). SLAMF1 downregulation was significantly associated with advanced Binet Stage (P = 0·001), CD38 positivity (P < 0·001), high β2‐microglobulin levels (P < 0·001), immunoglobulin heavy chain variable region gene (IGHV) unmutated status (P < 0·001), 11q deletion (P < 0·001), tumour protein p53 (TP53) disruption (P = 0·011) and higher risk CLL International Prognostic Index categories (P < 0·001). Multivariate analysis showed that downregulated SLAMF1 levels had independent negative prognostic impact on time‐to‐first treatment (P < 0·001) and overall survival (P < 0·001).
On the neutrality of the exchange rate regime regarding real misalignments: Evidence from sub‐Saharan Africa
Authors: Owoundi Ferdinand , Bikai Jacques Landry
Published: June 2020

This article provides further insights into the issue of real misalignments’ effects of exchange rate regimes. Our approach aims at comparing real exchange rate misalignments between countries with fixed regimes and those practicing alternative arrangements in sub‐Saharan Africa. To this end, we assess the equilibrium exchange rates based on two models of the equilibrium exchange rate, while using competing estimators and bothDe JureandDe Factoclassifications. Our results confirm the exchange rate regime neutrality regarding exchange rate misalignment, implying that the fixed regime is not prone to more misalignment within the sub‐region.
Oxiapoptophagy: A type of cell death induced by some oxysterols
Authors: Nury Thomas , Zarrouk Amira , Yammine Aline , Mackrill John J. , Vejux Anne , Lizard Gérard
Published: June 2020

Oxysterols are oxidized forms of cholesterol generated from cholesterol by auto‐oxidation, enzymatic processes, or both. Some of them (7‐ketocholesterol, 7β‐hydroxycholesterol and 24(S)‐hydroxycholesterol), when used at cytotoxic concentrations on different cell types from different species (mesenchymal bone marrow cells, monocytic cells and nerve cells), induce a type of cell death associated with OXIdative stress and several characteristics of APOPTOsis and autoPHAGY, defined as oxiapoptophagy. Oxidative stress is associated with overproduction of ROS, increased antioxidant enzyme activities, lipid peroxidation and protein carbonylation. Apoptosis is associated with activation of the mitochondrial pathway, opening of the mitochondrial permeability pore, loss of mitochondrial membrane potential, caspase‐3 activation, PARP degradation, nuclear condensation and/or fragmentation. Autophagy is characterized by autophagic vacuoles revealed by monodansylcadaverine staining and transmission electron microscopy, plus increased ratio of LC‐3II/LC‐3I. In addition, morphological, topographical and functional changes of the peroxisome are observed.

LINKED ARTICLES

This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc
A chalcone derivative, 1m‐6, exhibits atheroprotective effects by increasing cholesterol efflux and reducing inflammation‐induced endothelial dysfunction
Authors: Chen Liv Weichien , Tsai Min‐Chien , Chern Ching‐Yuh , Tsao Tien‐Ping , Lin Feng‐Yen , Chen Sy‐Jou , Tsui Pi‐Fen , Liu Yao‐Wen , Lu Hsien‐Jui , Wu Wan‐Lin , Lin Wei‐Shiang , Tsai Chien‐Sung , Lin Chin‐Sheng
Published: June 2020

Background and Purpose

Atherosclerosis, resulting from lipid dysregulation and vascular inflammation, causes atherosclerotic cardiovascular disease (ASCVD), which contributes to morbidity and mortality worldwide. Chalcone and its derivatives possess beneficial properties, including anti‐inflammatory, antioxidant and antitumour activity with unknown cardioprotective effects. We aimed to develop an effective chalcone derivative with antiatherogenic potential.

Experimental Approach

Human THP‐1 cells and HUVECs were used as in vitro models. Western blots and real‐time PCRs were performed to quantify protein, mRNA and miRNA expressions. The cholesterol efflux capacity was assayed by 3H labelling of cholesterol. LDL receptor knockout (Ldlr−/−) mice fed a high‐fat diet were used as an in vivo atherogenesis model. Haematoxylin and eosin and oil red O staining were used to analyse plaque formation.

Key Results

Using ATP‐binding cassette transporter A1 (ABCA1) expression we identified the chalcone derivative, 1m‐6, which enhances ABCA1 expression and promotes cholesterol efflux in THP‐1 macrophages. Moreover, 1m‐6 stabilizes ABCA1 mRNA and suppresses the expression of potential ABCA1‐regulating miRNAs through nuclear factor erythroid 2‐related factor 2 (Nrf2)/haem oxygenase‐1 (HO‐1) signalling. Additionally, 1m‐6 significantly inhibits TNF‐α‐induced expression of adhesion molecules, vascular cell adhesion molecule 1 (VCAM‐1) and intercellular adhesion molecule 1 (ICAM‐1), plus production of proinflammatory cytokines via inhibition of JAK/STAT3 activation and the modulation of Nrf2/HO‐1 signalling in HUVECs. In atherosclerosis‐prone mice, 1m‐6 significantly reduces lipid accumulation and atherosclerotic plaque formation.

Conclusion and Implications

Our study demonstrates that 1m‐6 produces promising atheroprotective effects by enhancing cholesterol efflux and suppressing inflammation‐induced endothelial dysfunction, which opens a new avenue for treating ASCVD.

LINKED ARTICLES

This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc
The suppressive effect on CD4 T cell alloresponse against endothelial HLA-DR via PD-L1 induced by anti-A/B ligation
Authors: Iwasaki K , Hamana H , Kishi H , Yamamoto T , Hiramitsu T , Okad M , Tomosugi T , Takeda A , Narumi S , Watarai Y , Miwa Y , Okumura M , Matsuoka Y , Horimi K , Muraguchi A , Kobayashi T
Published: June 2020

While donor-specific human leukocyte antigen (HLA) antibodies are a frequent cause for chronic antibody-mediated rejection in organ transplantation, this is not the case for antibodies targeting blood group antigens, as ABO-incompatible (ABO-I) organ transplantation has been associated with a favorable graft outcome. Here, we explored the role of CD4 T cell-mediated alloresponses against endothelial HLA-D-related (DR) in the presence of anti-HLA class I or anti-A/B antibodies. CD4 T cells, notably CD45RA-memory CD4 T cells, undergo extensive proliferation in response to endothelial HLA-DR. The CD4 T cell proliferative response was enhanced in the presence of anti-HLA class I, but attenuated in the presence of anti-A/B antibodies. Microarray analysis and molecular profiling demonstrated that the expression of CD274 programmed cell death ligand 1 (PD-L1) increased in response to anti-A/B ligation-mediated extracellular signal-regulated kinase (ERK) inactivation in endothelial cells that were detected even in the presence of interferon-γ stimulation. Anti-PD-1 antibody enhanced CD4 T cell proliferation, and blocked the suppressive effect of the anti-A/B antibodies. Educated CD25+CD127− regulatory T cells (edu.Tregs) were more effective at preventing CD4 T cell alloresponses to endothelial cells compared with naive Treg; anti-A/B antibodies were not involved in the Treg-mediated events. Finally, amplified expression of transcript encoding PD-L1 was observed in biopsy samples from ABO-I renal transplants when compared with those from ABO-identical/compatible transplants. Taken together, our findings identified a possible factor that might prevent graft rejection and thus contribute to a favorable outcome in ABO-I renal transplantation.
Effects of in vitro fertilization (IVF) therapies on metabolic, endocrine and inflammatory status in IVF‐conceived pregnancy
Authors: Coussa Ayla , Hasan Hayder A. , Barber Thomas M.
Published: June 2020

Rationale

In vitro fertilization (IVF) is a common treatment for infertility. In mice, IVF is associated with development of glucose intolerance. However, human data are limited regarding the metabolic, endocrine and inflammatory effects of IVF therapy in IVF‐conceived pregnancies.

Objective

To explore effects of IVF therapies on metabolic, endocrine and inflammatory parameters in IVF‐conceived pregnancy.

Methodology

Twelve‐week prospective observational study of adult normoglycaemic women, BMI 18.5‐38 kg/m2and ≤ 39 years awaiting IVF therapy. Fasting blood samples were collected at baseline and 12 weeks, and serum analysed for reproductive hormones, glucose, lipids, insulin sensitivity, thyroid status, adiponectin inflammatory marker and lipopolysaccharide‐binding protein (LBP).

Results

Two hundred and seventy‐five women were analysed: 158 IVF‐conceived pregnant women and 117 with failed IVF. Compared with baseline, nonpregnant women had significant (P < .001) increases in 12‐week glucose (86.04‐87.62 mg/dL), insulin (8.72‐9.37 µIU/mL), HOMA‐IR (1.9‐2.1), T‐Chol (169.5‐174.9 mg/dL), TG (71.0‐83.7 mg/dL) and HDL‐C (52.0‐54.11 mg/dL) levels. At 12 weeks, pregnant women also had (P < .001) increases in T‐Chol (177.5‐199.5 mg/dL), TG (73.5‐126.78 mg/dL) and HDL‐C (55.3‐65.1 mg/dL), while a significant reduction in glucose (86.15‐82.19 mg/dL), HbA1c (5.3‐5.08%) and TSH (1.71‐1.36 µIU/mL) levels from baseline. Adiponectin and LBP levels remained the same in either group.

Conclusion

In vitro fertilization hormonal therapy impairs glucose and insulin levels; these effects are masked in early pregnancy. Changes in lipid profile occur following IVF therapies regardless of pregnancy outcome. Neither adiponectin nor LBP is affected by IVF therapies and during early IVF‐conceived pregnancy.
Exosome biogenesis, secretion and function of exosomal miRNAs in skeletal muscle myogenesis
Authors: Yue Binglin , Yang Haiyan , Wang Jian , Ru Wenxiu , Wu Jiyao , Huang Yongzheng , Lan Xianyong , Lei Chuzhao , Chen Hong
Published: June 2020

Exosomes are membrane‐bound extracellular vesicles that are produced in the endosomal compartment of most mammalian cell types and then released. Exosomes are effective carriers for the intercellular material transfer of material that can influence a series of physiological and pathological processes in recipient cells. Among loaded cargoes, non‐coding RNAs (ncRNAs) vary for the exosome‐producing cell and its homeostatic state, and characterization of the biogenesis and secretion of exosomal ncRNAs and the functions of these ncRNAs in skeletal muscle myogenesis remain preliminary. In this review, we will describe what is currently known of exosome biogenesis, release and uptake of exosomal ncRNAs, as well as the varied functions of exosomal miRNAs in skeletal muscle myogenesis.
Quality assurance in melanoma care: guideline‐based quality indicators for melanoma – implementation, evaluation and update process
Authors: Follmann Markus , Eigentler Thomas , Adam Henning , Wenzel Gregor , Langer Thomas , Wesselmann Simone
Published: June 2020

Background

In 2018, an update of the German evidence‐based (S3) guidelines “Diagnosis, Therapy and Follow‐up of Melanoma” first issued in 2013 was published under the auspices of the German Guideline Program in Oncology. The update also included a revision of existing guideline‐based quality indicators (QIs).

Patients and methods

Using a standardized multi‐step process, the guideline‐derived QIs were revised by a multidisciplinary, interprofessional working group based on the strong (level A) recommendations contained in the guideline update as well as on a systematic literature search for international indicators and on the outcomes of existing QIs as reported by certified German skin cancer centers.

Results

Based on the original set of twelve guideline‐based QIs agreed upon in 2013, the working group developed an updated set containing nine indicators. Four QIs were kept unchanged; two were modified; two were removed; and three new QIs were added. Unlike 2013, the working group was now able to incorporate the outcomes of QIs previously implemented at the various skin cancer centers.

Conclusions

Close cooperation between guideline group and certification commission allows for the implementation of guideline‐based QIs in cancer care. Measured outcomes form the basis for updating both the guidelines and the QI development process. They provide information about the care of cancer patients in a real‐world setting as well as on guideline adherence and the feasibility of QIs themselves. This is a dynamic process that can be described in a transparent manner and that requires regular updating.
Congenital anomalies in children with pre‐ or perinatally acquired cerebral palsy: an international data linkage study
Authors: Goldsmith Shona , Mcintyre Sarah , Andersen Guro L , Gibson Catherine , Himmelmann Kate , Blair Eve , Badawi Nadia , Smithers‐Sheedy Hayley , Garne Ester ,   the Comprehensive CA‐CP Study Group*
Published: June 2020

Aim

To describe the frequency and types of major congenital anomalies present in children with pre‐ or perinatally acquired cerebral palsy (CP), and compare clinical outcomes for children with and without anomalies.

Method

This multi‐centre total population collaborative study between Surveillance of Cerebral Palsy in Europe, Australian Cerebral Palsy Register, and European Surveillance of Congenital Anomalies (EUROCAT) involved six European and three Australian regions. Data were linked between each region’s CP and congenital anomaly register for children born between 1991 and 2009, and then pooled. Children were classified into mutually exclusive categories based on type of anomaly. Proportions of children with congenital anomalies were calculated, and clinical outcomes compared between children with and without anomalies.

Results

Of 8201 children with CP, 22.8% (95% confidence interval [CI] 21.9, 23.8) had a major congenital anomaly. Isolated cerebral anomalies were most common (45.2%), with a further 8.6% having both cerebral and non‐cerebral anomalies. Cardiac anomalies only were described in 10.5% of children and anomalies associated with syndromes were also reported: genetic (8.0%), chromosomal (5.7%), and teratogenic (3.0%). Clinical outcomes were more severe for children with CP and congenital anomalies, particularly cerebral anomalies.

Interpretation

This large, international study reports major congenital anomalies in nearly one‐quarter of children with pre‐ or perinatally acquired CP. Future research must focus on aetiological pathways to CP that include specific patterns of congenital anomalies.

What this paper adds

Congenital anomalies were reported in 23% of children with pre‐ or perinatally acquired cerebral palsy.

A higher proportion of children born at or near term had anomalies.

The most common type of anomalies were isolated cerebral anomalies.

Clinical outcomes were more severe for children with congenital anomalies (particularly cerebral).
Resource Discovery and the Political Fortunes of National Leaders
Authors: Bhattacharyya Sambit , Keller Michael
Published: June 2020

We investigate the causal effects ofgiantandfirstoil and mineral discoveries on the political fortunes of national leaders using a large dataset of 1255 leaders in 158 countries over the period 1950 to 2010 insingle‐riskandmultiple‐riskdiscrete time proportional hazard models. We find that mineral discoveries reduce risk for the incumbent in a single‐risk model especially in a non‐election year. In contrast, oil discoveries reduce risk disproportionately more in countries with weak political institutions. The effects appear to be induced by resource income rather than expectations. In a multiple‐risk model, oil discovery significantly reduces the risk of departure via military coup while resource discovery reduces the risk of resignation. Resource discovery does not seem to affect the risk of election loss. Non‐resource tax and military expenditure appear to be two potent mechanisms through which oil discovery affects political survival.
WHAT DRIVES SECOND GENERATION SUCCESS? THE ROLES OF EDUCATION, CULTURE, AND CONTEXT
Authors: Deutscher Nathan
Published: June 2020

I explore differences in intergenerational income mobility among second generation Australians—why do some communities do better or worse than would be expected from first generation incomes alone? I present a new decomposition of this exceptional income mobility, finding exceptional educational mobility drives many of these differences. Drawing on rich survey and test score data, I provide evidence that educational mobility partly reflects a role for culture—but also the wider context of migration. In particular, migrants facing higher first generation income penalties tend to aspire to and acquire more education, and see it as more important to success. (JEL J62, F22, I2)
Embryogenesis plasticity and the transmission of maternal effects in Daphnia pulex
Authors: Hasoon Megan S. R. , Plaistow Stewart J.
Published: June 2020

Understanding how genetic, nongenetic, and environmental cues are integrated during development may be critical in understanding if, and how, organisms will respond to rapid environmental change. Normally, only post‐embryonic studies are possible. But in this study, we developed a real‐time, high‐throughput confocal microscope assay that allowed us to link Daphnia embryogenesis to offspring life history variation at the individual level. Our assay identified eight clear developmental phenotypes linked by seven developmental stages, the duration of which were correlated with the expression of specific offspring life history traits. Daphnia embryogenesis varied not only between clones reared in the same environment, but also within a single clone when mothers were of different ages or reared in different food environments. Our results support the hypothesis that Daphnia embryogenesis is plastic and can be altered by changes in maternal state or maternal environment. As well as furthering our understanding of the mechanisms underpinning parental effects, our assay may also have an industrial application if it can be used as a rapid ecotoxicological prescreen for testing the effect that pollutant doses have on offspring life histories traditionally assayed with a 21‐day Daphnia reproduction test.
The upper thermal tolerance for a Texas population of the hairy maggot blow fly Chrysomya rufifacies Macquart (Diptera: Calliphoridae)
Authors: Rusch Travis W. , Faris Ashleigh M. , Beebe Lauren E. J. , Tomberlin Jeffery K. , Tarone Aaron M.
Published: June 2020

The hairy maggot blow fly (Chrysomya rufifacies: Macquart) is an invasive necrophagous fly found throughout the continental United States. Chrysomya rufifacies is of medical/veterinary, forensic, and ecological importance due to its ability to cause myiasis, colonise human remains, and displace native Diptera. However, little is known about their upper thermal tolerance, which could be used to better predict their invasion potential.

We investigated the upper thermal tolerance of C. rufifacies exposed to different temperatures (20–45 °C), times (1–6 h), and nutrients (no food or water, water only, or a food‐water mixture) for both sexes and two age ranges (young = 6–8 days post pupal emergence; old = 9–11 days post pupal emergence).

As temperature or duration increased, the probability of knockdown increased (0–100% at 20 and 45 °C and from 41 to 75% at 1 and 6 h), while the probability of survival decreased (99–2% at 20 and 45 °C and from 75 to 28% at 1 and 6 h). The availability of nutrients increased thermal tolerance at moderate temperatures (40 and 42 °C). Female flies were more thermally tolerant than males (probability of knockdown = 49% vs 58%; probability of survival = 58% vs 46%). Thermal tolerance did not differ by age.

These data reveal details about the upper thermal tolerance for a single population of C. rufifacies, and suggest that environmental and organismal factors ought to be considered in order to make meaningful predictions about the invasion potential of C. rufifacies in North America.
Increasing connectivity of Great Lakes tributaries: Interspecific and intraspecific effects on resident brook trout and brown trout populations
Authors: Zorn Troy G. , Hessenauer Jan‐Michael , Wills Todd C.
Published: June 2020

Understanding resident fish population responses to restored connectivity would enhance decision‐making on dam removal and fish passage. Since such evaluations are limited in the Great Lakes region of North America, we compared abundance, survival, and growth of resident brook trout and brown trout between sets of Michigan streams where populations were or were not interacting with salmonid species that might be present if connectivity existed. We analysed data from 34 electrofishing index sites to compare resident trout populations between streams without versus with Great Lakes access (and migratory Pacific salmonids), and brook trout populations in Great Lakes inaccessible (land‐locked) streams where brown trout were present versus absent. Great Lakes accessibility effects on fish density became increasingly positive for older age groups of brown trout while generally negative for all age classes of brook trout. Brown trout had consistently negative effects on brook trout density in land‐locked streams. Increased connectivity had significant effects on annual survival for only one of seven trout age classes modelled, while intraspecific density‐dependent effects on survival were significant in six models. Significant intraspecific effects on resident trout growth occurred for seven of eleven age classes examined. Negative interspecific effects of Great Lakes access on resident trout growth were most noticeable for age‐0 and age‐1 resident trout, age classes that likely compete with juvenile Pacific salmonids. Our findings provide a more robust understanding of how Great Lakes connectivity affects resident trout populations, highlighting negative influences of brown trout on brook trout and intraspecific density‐dependent effects.
Romantic relationship group intervention for men with early psychosis: A feasibility, acceptability and potential impact pilot study
Authors: Hache‐Labelle Catherine , Abdel‐Baki Amal , Lepage Martin , Laurin Anne‐Sophie , Guillou Amili , Francoeur Audrey , Bergeron Sophie , Lecomte Tania
Published: June 2020

Aim

To assess the feasibility, acceptability and potential impact of a cognitive behavioural group intervention occurring over 12 sessions and focusing on romantic relationships for single men with early psychosis.

Methods

Recruitment, drop‐out and participation rates were collected. An A‐B‐A within‐subject design (n = 7), where each participant acted as his own control, was used to determine potential impact (on social functioning, romantic relationship functioning, self‐esteem, theory of mind [ToM] and self‐stigma) across time (six time points).

Results

Feasibility and acceptability were established. As for the potential impact of the intervention, participants did not all evolve the same way. Improvements were found on social functioning (“behaviours” subscale), romantic relationship functioning and ToM (“mentalizing” subscale).

Conclusions

More studies are warranted to expand on these results and to further help men with early psychosis in their social and romantic development.
Functional analysis of CX3CR1 in human induced pluripotent stem (iPS) cell‐derived microglia‐like cells
Authors: Murai Nobuhito , Mitalipova Maisam , Jaenisch Rudolf
Published: June 2020

Microglia are the primary immune cells of the central nervous system and crucial to proper development and maintenance of the brain. Microglia have been recognized to be associated with neurodegenerative diseases and neuroinflammatory disorders. CX3C chemokine receptor 1 (CX3CR1), which is specifically expressed in microglia, regulates microglia homeostatic functions such as microglial activation and is downregulated in aged brain and disease‐associated microglia in rodents, yet its role in human microglia is not fully understood. In this study, we investigated the function of CX3CR1 in human microglia using human induced pluripotent stem (iPS) cell‐derived microglia‐like cells. Human iPS cell‐derived microglia‐like cells expressed microglial markers and showed an activated state and phagocytic activity. Using CRISPR/Cas9 genome editing, we deleted CX3CR1 in human iPS cells and found increased inflammatory responses and phagocytic activity in mutant as compared to wild‐type microglia‐like cells. In addition, the CX3C chemokine ligand 1 (CX3CL1, a ligand for CX3CR1) significantly decreased the upregulation of IL‐6 by lipopolysaccharide stimulation in human iPS cell‐derived microglia‐like cells. These results suggest that CX3CR1 in human microglia may contribute to microglial homeostasis by regulating inflammatory response and phagocytosis.