bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of different general anaesthetics on ventricular repolarisation in robot‐assisted laparoscopic prostatectomy
Authors: Park Jin Ha , Lee Ki‐Young , Choi Young Deuk , Lee Jongsoo , Shin Hye Jung , Han Dong Woo , Baek Jiwon , Kim So Yeon
Published: June 2020

Background

Ventricular repolarisation is affected differently by the types of anaesthetics used. This study aimed to compare the effect of different types of anaesthetics on ventricular repolarisation during robot‐assisted laparoscopic radical prostatectomy (RALP).

Methods

Sixty‐nine patients were randomly assigned in a 1:1:1 ratio to the Sevoflurane (sevoflurane/remifentanil), Desflurane (desflurane/remifentanil) or total intravenous anaesthesia (TIVA [propofol/remifentanil]) groups; however, only 67 patients completed the study. The primary outcome was heart rate‐corrected QT (QTc) interval collected at nine time points during RALP. Bazett’s (QTcB) and Fridericia’s (QTcF) formulae were used for QT interval correction. The secondary outcomes were Tpeak‐Tend (Tp‐e) interval and Tp‐e/QT ratio that were collected at the same time points.

Results

The QTcB and QTcF intervals were significantly prolonged during surgery in all groups; however, these values showed significant intergroup differences with time. After assuming the Trendelenburg position, the QTcB and QTcF intervals were significantly longer in the Desflurane group than in the other two groups, and this prolongation continued until the end of surgery. Intra‐operatively, the QTcB and QTcF intervals exceeded 450 ms in six and five patients, respectively, in the Desflurane group, but in none in the TIVA group. Moreover, the incidence of intra‐operative QTc interval prolongation >20 ms and >60 ms was significantly higher in the Desflurane group than in the TIVA group. There were no significant differences in Tp‐e intervals and Tp‐e/QT ratio among the three groups during surgery.

Conclusions

To minimise QTc interval prolongation during RALP, TIVA with propofol/remifentanil is recommended for general anaesthesia.
Impact of mechanical circulatory support on pediatric heart transplant candidates with elevated pulmonary vascular resistance
Authors: Thangappan Karthik , Morales David L. S. , Vu Quyen , Lehenbauer David , Villa Chet , Wittekind Samuel , Hirsch Russel , Lorts Angela , Zafar Farhan
Published: June 2020

With the new era of increasing use of mechanical circulatory support (MCS) in children, seemingly more patients with elevated pulmonary vascular resistance (PVR) are having positive outcomes. The purpose of this study was to define the effect of MCS on pediatric patients listed for heart transplant with an elevated PVR. The United Network for Organ Sharing (UNOS) database was used to identify patients aged 0‐18 at the time of listing for heart transplant between 2010 and 2019 who had PVR documented (n = 2081). Patients were divided into MCS (LVAD, RVAD, BiVAD, and TAH) and No MCS groups, then divided by PVR (PVR) at the time of listing: <3, 3‐6, and >6 Wood units (WU). MCS was used in 20% overall (n = 426); 57% of those with PVR <3, 27% with PVR 3‐6, and 16% with PVR >6. MCS, PVR <3 patients had a higher chance of positive waitlist outcome than all No MCS groups (vs. PVR <3, P = .049; vs. PVR 3‐6, P = .004; vs. PVR >6, P < .001). MCS, PVR 3‐6 patients had a higher chance of positive waitlist outcome than all No MCS groups (vs. PVR <3, P = .048; vs. PVR 3‐6, P = .009; vs. PVR >6, P < .001). MCS, PVR >6 patients had a higher chance of positive waitlist outcome than No MCS, PVR >6 patients (P = .012). Within the No MCS group, patients with a PVR >6 had a higher incidence of negative waitlist outcome compared to PVR <3 (17% vs. 10%, P = .002); this was not the case in the MCS group (5% vs. 6%, P = .693). More patients in the MCS group were ventilator dependent (15% vs. 9%, P < .001) at the time of listing and less likely to have a functional status >50% (43% vs. 73%, P < .001). No significant differences in post‐transplant survival were found in pairwise comparisons of MCS and No MCS PVR subgroups. Patients supported with MCS had a significantly higher chance of a positive waitlist outcome than those without such support regardless of PVR status. This was most pronounced with a PVR greater than 6 WU. MCS compared to No MCS patients had better waitlist survival and equivalent post‐transplant survival. MCS patients, despite being more ill, had better overall survival regardless of PVR.
The impact of obesity on outcomes in patients receiving extracorporeal life support
Authors: Christian‐Miller Nathaniel , Hadaya Joseph , Nakhla Morcos , Sanaiha Yas , Madrigal Josef , Emami Sara , Cale Mario , Sareh Sohail , Benharash Peyman
Published: June 2020

Extracorporeal life support (ECLS) has been increasingly utilized to manage cardiac and pulmonary dysfunction. The impact of obesity on outcomes of ECLS is poorly defined. The purpose of the study was to compare in‐hospital mortality, resource use, complications, and readmissions in obese versus non‐obese patients receiving ECLS. We performed a retrospective cohort study of all adult ECLS patients with and without an obesity diagnosis using the 2010–2016 Nationwide Readmissions Database (NRD). Mortality, length of stay (LOS), hospital charges, complications, and readmissions were evaluated using multivariable logistic and linear regression. Of 23 876, patients who received ECLS, 1924 (8.1%) were obese. Obese patients received ECLS more frequently for respiratory failure (29.5% vs. 23.7%, P = .001). After adjustment for patient and hospital factors, obesity was not associated with increased odds of mortality (AOR = 1.06, P = .44) and was associated with decreased LOS (13.7 vs. 21.2 days, P < .001), hospital charges ($171 866 vs. $211 445, P < .001), and 30‐day readmission (AOR = 0.71, P = .03). Obesity was also associated with reduced odds of hemorrhage (AOR = 0.43, P < .001), neurologic complications (AOR = 0.55, P = .004), and acute kidney injury (AOR=0.83, P = .04). After stratification by ECLS indication, obesity remained predictive of shorter LOS (AOR range: 0.53‐0.78, all P < .05 ) and did not impact mortality (all P > .05). Respiratory support remains the most common indication for ECLS among obese patients. Among all patients, as well as by individual ECLS indication, obesity was not associated with increased odds of mortality. These findings suggest that obesity should not be considered a high‐risk contraindication to ECLS.
Scotland's 2009–2015 methadone‐prescription cohort: Quintiles for daily dose of prescribed methadone and risk of methadone‐specific death
Authors: Gao Lu , Robertson J. Roy , Bird Sheila M.
Published: June 2020

Aims

As methadone clients age, their drug‐related death (DRD) risks increase, more than doubling at 45+ years for methadone‐specific DRDs.

Methods

Using Community Health Index (CHI) numbers, mortality to 31 December 2015 was ascertained for 36 347 methadone‐prescription clients in Scotland during 2009–2015. Cohort entry, quantity of prescribed methadone and daily dose (actual or recovered by effective, simple rules) were defined by clients' first CHI‐identified methadone prescription after 30 June 2009 and used in proportional hazards analysis. As custodian of death records, National Records of Scotland identified non‐DRDs from DRDs. Methadone‐specific DRD means methadone was implicated but neither heroin nor buprenorphine.

Results

The cohort's 192 928 person‐years included 1857 non‐DRDs and 1323 DRDs (42%), 546 of which were methadone specific. Actual/recovered daily dose was available for 26 533 (73%) clients who experienced 420 methadone‐specific DRDs. Top quintile for daily dose at first CHI‐identified methadone prescription was >90 mg. Age 45+ years at cohort‐entry (hazard ratio vs 25–34 years: 3.1, 95% confidence interval: 2.4–4.2), top quintile for baseline daily dose of prescribed methadone (vs 50–70 mg: 1.9, 1.1–3.1) and being female (1.3, 1.0–1.6) significantly increased clients' risk of methadone‐specific DRD.

Conclusion

Extra care is needed when methadone daily dose exceeds 90 mg. Females' higher risk for methadone‐specific DRD is new and needs validation. Further analyses of prescribed daily dose linked to mortality for large cohorts of methadone clients are needed internationally, together with greater pharmacodynamic and pharmacokinetic understanding of methadone by age and sex. Balancing age‐related risks is challenging for prescribers who manage chronic opiate dependency against additional uncertainty about the nature, strength and pharmacological characteristics of drugs from illegal markets.
C1 esterase inhibitor and the contact system in COVID‐19
Authors: Thomson Timothy M. , Toscano‐Guerra Emily , Casis Ernesto , Paciucci Rosanna
Published: June 2020

Coronavirus disease 2019 (COVID‐19) is frequently associated with severe systemic consequences, including vasculitis, a hyperinflammatory state and hypercoagulation. The mechanisms leading to these life‐threatening abnormalities are multifactorial. Based on the analysis of publicly available interactomes, we propose that severe acute respiratory syndrome coronavirus‐2 infection directly causes a deficiency in C1 esterase inhibitor, a pathogen‐specific mechanism that may help explain significant systemic abnormalities in patients with COVID‐19.
Tumor‐associated macrophage‐derived inflammatory cytokine enhances malignant potential of malignant pleural mesothelioma
Authors: Horio Daisuke , Minami Toshiyuki , Kitai Hidemi , Ishigaki Hirotoshi , Higashiguchi Yoko , Kondo Nobuyuki , Hirota Seiichi , Kitajima Kazuhiro , Nakajima Yasuhiro , Koda Yuichi , Fujimoto Eriko , Negi Yoshiki , Niki Maiko , Kanemura Shingo , Shibata Eisuke , Mikami Koji , Takahashi Ryo , Yokoi Takashi , Kuribayashi Kozo , Kijima Takashi
Published: June 2020

Malignant pleural mesothelioma (MPM) is an asbestos‐related aggressive malignant neoplasm. Due to the difficulty of achieving curative surgical resection in most patients with MPM, a combination chemotherapy of cisplatin and pemetrexed has been the only approved regimen proven to improve the prognosis of MPM. However, the median overall survival time is at most 12 mo even with this regimen. There has been therefore a pressing need to develop a novel chemotherapeutic strategy to bring about a better outcome for MPM. We found that expression of interleukin‐1 receptor (IL‐1R) was upregulated in MPM cells compared with normal mesothelial cells. We also investigated the biological significance of the interaction between pro‐inflammatory cytokine IL‐1β and the IL‐1R in MPM cells. Stimulation by IL‐1β promoted MPM cells to form spheroids along with upregulating a cancer stem cell marker CD26. We also identified tumor‐associated macrophages (TAMs) as the major source of IL‐1β in the MPM microenvironment. Both high mobility group box 1 derived from MPM cells and the asbestos‐activated inflammasome in TAMs induced the production of IL‐1β, which resulted in enhancement of the malignant potential of MPM. We further performed immunohistochemical analysis using clinical MPM samples obtained from patients who were treated with the combination of platinum plus pemetrexed, and found that the overexpression of IL‐1R tended to correlate with poor overall survival. In conclusion, the interaction between MPM cells and TAMs through a IL‐1β/IL‐1R signal could be a promising candidate as the target for novel treatment of MPM (Hyogo College of Medicine clinical trial registration number: 2973).
Hypertonic saline mediates the NLRP3/IL‐1β signaling axis in microglia to alleviate ischemic blood‐brain barrier permeability by downregulating astrocyte‐derived VEGF in rats
Authors: Wang Qiao‐sheng , Ding Hong‐guang , Chen Sheng‐long , Liu Xin‐qiang , Deng Yi‐yu , Jiang Wen‐qiang , Li Ya , Huang Lin‐qiang , Han Yong‐li , Wen Miao‐yun , Wang Mei‐qiu , Zeng Hong‐ke
Published: June 2020

Introduction

The aim of this study was to explore whether the antibrain edema of hypertonic saline (HS) is associated with alleviating ischemic blood‐brain barrier (BBB) permeability by downregulating astrocyte‐derived vascular endothelial growth factor (VEGF), which is mediated by microglia‐derived NOD‐like receptor protein 3 (NLRP3) inflammasome.

Methods

The infarct volume and BBB permeability were detected. The protein expression level of VEGF in astrocytes in a transient focal brain ischemia model of rats was evaluated after 10% HS treatment. Changes in the NLRP3 inflammasome, IL‐1β protein expression, and the interleukin‐1 receptor (IL1R1)/pNF‐кBp65/VEGF signaling pathway were determined in astrocytes.

Results

HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulates IL‐1β expression by inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulates VEGF expression by inhibiting the phosphorylation of NF‐кBp65 mediated by IL‐1β in astrocytes.

Conclusions

HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulated IL‐1β expression via inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulated VEGF expression through inhibiting the phosphorylation of NF‐кBp65 mediated by IL‐1β in astrocytes.
FDG PET/CT of the non‐malignant liver in an increasingly obese world population
Authors: Keramida Georgia , Peters A. Michael
Published: June 2020

Because of obesity, non‐alcoholic fatty liver disease (NAFLD) is becoming increasingly important. 10% of NAFLD patients develop non‐alcoholic steatohepatitis (NASH), which may progress to cirrhosis and is now the leading indication for liver transplantation in the Western world. Prefibrotic NASH can only be reliably diagnosed by biopsy. However, given its success in other inflammatory diseases, PET/CT with 18F‐fluorodeoxyglucose (FDG), although non‐specific, may offer a promising approach to diagnosing not only NASH but also other inflammatory liver conditions. In addition, FDG PET has generated pathophysiological information on hepatic glucose metabolism and, diagnostically, used liver for quantification of tumour FDG accumulation (e.g. Deauville scoring). A review of hepatic FDG PET is therefore timely. There are two general approaches to the quantification of hepatic FDG accumulation: firstly, standard uptake value (SUV) and secondly dynamic PET. SUV is a poor index of hepatic metabolic function because most hepatic FDG (~75%) is un‐phosphorylated 60‐min postinjection. Hepatic fat is increased in NAFLD but accumulates negligible FDG. Because fat distribution is heterogeneous, maximum pixel SUV is therefore preferred to mean pixel SUV. Computer modelling of dynamic PET dissects the transport constants governing hepatic FDG kinetics but is challenged by the liver's dual blood supply. Graphical analysis is less informative but more robust and will be the preferred clinical approach to measurement of hepatic FDG phosphorylation. Previous dynamic PET studies have ignored hepatic fat and therefore potentially underestimated glucose accumulation in patients with hepatic steatosis. Future work should use graphical analysis of dynamic PET and correction for hepatic fat.
A review on methods for diagnosis of breast cancer cells and tissues
Authors: He Ziyu , Chen Zhu , Tan Miduo , Elingarami Sauli , Liu Yuan , Li Taotao , Deng Yan , He Nongyue , Li Song , Fu Juan , Li Wen
Published: June 2020

Breast cancer has seriously been threatening physical and mental health of women in the world, and its morbidity and mortality also show clearly upward trend in China over time. Through inquiry, we find that survival rate of patients with early‐stage breast cancer is significantly higher than those with middle‐ and late‐stage breast cancer, hence, it is essential to conduct research to quickly diagnose breast cancer. Until now, many methods for diagnosing breast cancer have been developed, mainly based on imaging and molecular biotechnology examination. These methods have great contributions in screening and confirmation of breast cancer. In this review article, we introduce and elaborate the advances of these methods, and then conclude some gold standard diagnostic methods for certain breast cancer patients. We lastly discuss how to choose the most suitable diagnostic methods for breast cancer patients. In general, this article not only summarizes application and development of these diagnostic methods, but also provides the guidance for researchers who work on diagnosis of breast cancer.
Emerging role of targeting macrophages in rheumatoid arthritis: Focus on polarization, metabolism and apoptosis
Authors: Yang Xuezhi , Chang Yan , Wei Wei
Published: June 2020

Macrophages maintain a dynamic balance in physiology. Various known or unknown microenvironmental signals influence the polarization, activation and death of macrophages, which creates an imbalance that leads to disease. Rheumatoid arthritis (RA) is characterized by the massive infiltration of a variety of chronic inflammatory cells in synovia. Abundant activated macrophages found in RA synovia are an early hallmark of RA, and the number of these macrophages can be decreased after effective treatment. In RA, the proportion of M1 (pro‐inflammatory macrophages) is higher than that of M2 (anti‐inflammatory macrophages). The increased pro‐inflammatory ability of macrophages is related to their excessive activation and proliferation as well as an enhanced anti‐apoptosis ability. At present, there are no clinical therapies specific to macrophages in RA. Understanding the mechanisms and functional consequences of the heterogeneity of macrophages will aid in confirming their potential role in inflammation development. This review will outline RA‐related macrophage properties (focus on polarization, metabolism and apoptosis) as well as the origin of macrophages. The molecular mechanisms that drive macrophage properties also be elucidated to identify novel therapeutic targets for RA and other autoimmune disease.
Endoscopic muscularis dissection for gastrointestinal mesenchymal tumor
Authors: Sawada Atsushi , Hirasawa Kingo , Maeda Shin
Published: June 2020

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Diagnostic performance for T1 cancer in colorectal lesions ≥10 mm by optical characterization using magnifying narrow‐band imaging combined with magnifying chromoendoscopy; implications for optimized stratification by Japan Narrow‐band Imaging Expert Team classification
Authors: Hosotani Kazuya , Imai Kenichiro , Hotta Kinichi , Ito Sayo , Kishida Yoshihiro , Yabuuchi Yohei , Yoshida Masao , Kawata Noboru , Kakushima Naomi , Takizawa Kohei , Ishiwatari Hirotoshi , Matsubayashi Hiroyuki , Ono Hiroyuki
Published: June 2020

Background

Magnifying narrow‐band imaging (M‐NBI) and magnifying chromoendoscopy (M‐CE) enable accurate diagnosis of T1 colorectal cancer, but the diagnostic yields from combined M‐NBI and CE have not been fully analyzed. We aimed to evaluate the diagnostic yield of combining Japan NBI Expert Team (JNET) classification using M‐NBI and M‐CE.

Methods

Superficial colorectal lesions ≥10 mm removed at a Japanese tertiary cancer center between February 2016 and December 2018 were included. We analyzed the relationship between JNET classification, M‐CE findings, and histological results based on prospectively collected endoscopic and pathologic data.

Results

A total of 1573 lesions, including 56 superficial submucosal invasive cancers, 160 deep submucosal invasive cancers, and 81 advanced cancers (≥T2) were analyzed. The probability of deeply invasive cancer (95% confidence interval) was 1.8% (1.1–2.8), 30.1% (25.4–35.1), and 96.6% (91.5–99.1) in JNET Types 2A, 2B, and 3, respectively. The probability of deeply invasive cancer in JNET Type 2B lesions with non‐V, VL, and VH pit pattern was 4.3%, 16.6%, 76.0%, respectively (P < 0.001).

Conclusions

Our study showed the stratification by M‐NBI using JNET classification and the effect of additional M‐CE for JNET Type 2B lesions.
Risk factors and outcomes of anxiety symptom trajectories in type 2 diabetes: the Fremantle Diabetes Study Phase II
Authors: Whitworth S. R. , Bruce D. G. , Starkstein S. E. , Davis T. M. E. , Skinner T. C. , Davis W. A. , Bucks R. S.
Published: June 2020

Aim

To identify determinants and outcomes of 4‐year trajectories of anxiety symptoms in a community‐based cohort with type 2 diabetes.

Methods

Some 1091 participants in the Fremantle Diabetes Study‐Phase II with type 2 diabetes completed the Generalized Anxiety Disorder Scale at baseline and biennially for 4 years, in addition to psychological, biomedical and self‐management measures. Latent growth mixture modelling identified trajectories of anxiety symptom severity, and regression models determined predictors of trajectory membership and associated outcomes.

Results

Two distinct groups of participants were identified: those with continuously low–no anxiety symptoms (87%) and those with improving but consistently high anxiety symptoms (elevated anxiety; 13%). Higher HbA1c and BMI, macrovascular complications and a history of generalized anxiety and/or major depressive disorder increased the risk of elevated anxiety. Elevated anxiety did not predict change in health‐related outcomes over time. Elevated anxiety and depression symptoms were highly comorbid and those with both displayed the most persistent anxiety symptoms.

Conclusions

A subgroup of individuals with type 2 diabetes are at risk of persistently elevated anxiety symptoms. Routine monitoring of the severity of psychological symptoms over time in this population should facilitate earlier and more intensive mood management.
Teaching dental anatomy & morphology: An updated clinical‐ & digital‐based learning module
Authors: Abdalla Rowida
Published: June 2020

Introduction

Dental Anatomy and morphology learning is an essential component of the dental curriculum; students introduced to dental morphology in a detailed textbook style lecture format often have difficulty transferring that knowledge to the associated clinically related activities. The purpose of this article is to describe the rationale, components and advantages of an updated dental anatomy module and present a comparison of student course evaluations for those who received the updated module (CDM) versus those who received the traditional module (TM).

Method

An updated module was implemented at the University of Kentucky College of Dentistry (UKCD). The updated module consisted of clinically based lectures and incorporated digital technologies in both lecture and laboratory portions of the course as well as a patient‐based aesthetic wax‐up exercise. The goal of the updated module is to shift emphasis away from decontextualised technical learning towards more active and clinically applicable learning that improves classroom interaction and takes advantage of the current technologies available.

Results

The results were statistically analysed using a two‐sample t test. The updated module was statistically significantly highly rated by students.

Conclusion

The updated module was highly appreciated and rated by students. An update to the educational method of teaching dental anatomy and morphology is proposed, clinical dental anatomy teaching results in enhanced students’ engagement and assessment. More research and proper strategic planning for implementation of digital technology into the dental anatomy curriculum are needed to adequately utilise these resources.
Integrin adhesion in brain assembly: From molecular structure to neuropsychiatric disorders
Authors: Jaudon Fanny , Thalhammer Agnes , Cingolani Lorenzo A.
Published: June 2020

Integrins are extracellular matrix receptors that mediate biochemical and mechanical bi‐directional signals between the extracellular and intracellular environment of a cell thanks to allosteric conformational changes. In the brain, they are found in both neurons and glial cells, where they play essential roles in several aspects of brain development and function, such as cell migration, axon guidance, synaptogenesis, synaptic plasticity and neuro‐inflammation. Although there are many successful examples of how regulating integrin adhesion and signaling can be used for therapeutic purposes, for example for halting tumor progression, this is not the case for the brain, where the growing evidence of the importance of integrins for brain pathophysiology has not translated yet into medical applications. Here, we review recent literature showing how alterations in integrin structure, expression and signaling may be involved in the etiology of autism spectrum disorder, epilepsy, schizophrenia, addiction, depression and Alzheimer's disease. We focus on common mechanisms and recurrent signaling pathways, trying to bridge studies on the genetics and molecular structure of integrins with those on synaptic physiology and brain pathology. Further, we discuss integrin‐targeting strategies and their potential benefits for therapeutic purposes in neuropsychiatric disorders.
The function of apolipoproteins L (APOLs): relevance for kidney disease, neurotransmission disorders, cancer and viral infection
Authors: Pays Etienne
Published: June 2020

The discovery that apolipoprotein L1 (APOL1) is the trypanolytic factor of human serum raised interest about the function of APOLs, especially following the unexpected finding that in addition to their protective action against sleeping sickness, APOL1 C‐terminal variants also cause kidney disease. Based on the analysis of the structure and trypanolytic activity of APOL1, it was proposed that APOLs could function as ion channels of intracellular membranes and be involved in mechanisms triggering programmed cell death. In this review, the recent finding that APOL1 and APOL3 inversely control the synthesis of phosphatidylinositol‐4‐phosphate (PI(4)P) by the Golgi PI(4)‐kinase IIIB (PI4KB) is commented. APOL3 promotes Ca2+‐dependent activation of PI4KB, but due to their increased interaction with APOL3, APOL1 C‐terminal variants can inactivate APOL3, leading to reduction of Golgi PI(4)P synthesis. The impact of APOLs on several pathological processes that depend on Golgi PI(4)P levels is discussed. I propose that through their effect on PI4KB activity, APOLs control not only actomyosin activities related to vesicular trafficking, but also the generation and elongation of autophagosomes induced by inflammation.
Supply and demand—heme synthesis, salvage and utilization by Apicomplexa
Authors: Kloehn Joachim , Harding Clare R. , Soldati‐Favre Dominique
Published: June 2020

The Apicomplexa phylum groups important human and animal pathogens that cause severe diseases, encompassing malaria, toxoplasmosis, and cryptosporidiosis. In common with most organisms, apicomplexans rely on heme as cofactor for several enzymes, including cytochromes of the electron transport chain. This heme derives from de novo synthesis and/or the development of uptake mechanisms to scavenge heme from their host. Recent studies have revealed that heme synthesis is essential for Toxoplasma gondii tachyzoites, as well as for the mosquito and liver stages of Plasmodium spp. In contrast, the erythrocytic stages of the malaria parasites rely on scavenging heme from the host red blood cell. The unusual heme synthesis pathway in Apicomplexa spans three cellular compartments and comprises enzymes of distinct ancestral origin, providing promising drug targets. Remarkably given the requirement for heme, T. gondii can tolerate the loss of several heme synthesis enzymes at a high fitness cost, while the ferrochelatase is essential for survival. These findings indicate that T. gondii is capable of salvaging heme precursors from its host. Furthermore, heme is implicated in the activation of the key antimalarial drug artemisinin. Recent findings established that a reduction in heme availability corresponds to decreased sensitivity to artemisinin in T. gondii and Plasmodium falciparum, providing insights into the possible development of combination therapies to tackle apicomplexan parasites. This review describes the microeconomics of heme in Apicomplexa, from supply, either from de novo synthesis or scavenging, to demand by metabolic pathways, including the electron transport chain.
Wildfire combustion and carbon stocks in the southern Canadian boreal forest: Implications for a warming world
Authors: Dieleman Catherine M. , Rogers Brendan M. , Potter Stefano , Veraverbeke Sander , Johnstone Jill F. , Laflamme Jocelyne , Solvik Kylen , Walker Xanthe J. , Mack Michelle C. , Turetsky Merritt R.
Published: June 2020

Boreal wildfires are increasing in intensity, extent, and frequency, potentially intensifying carbon emissions and transitioning the region from a globally significant carbon sink to a source. The productive southern boreal forests of central Canada already experience relatively high frequencies of fire, and as such may serve as an analog of future carbon dynamics for more northern forests. Fire–carbon dynamics in southern boreal systems are relatively understudied, with limited investigation into the drivers of pre‐fire carbon stocks or subsequent combustion. As part of NASA's Arctic‐Boreal Vulnerability Experiment, we sampled 79 stands (47 burned, 32 unburned) throughout central Saskatchewan to characterize above‐ and belowground carbon stocks and combustion rates in relation to historical land use, vegetation characteristics, and geophysical attributes. We found southern boreal forests emitted an average of 3.3 ± 1.1 kg C/m2from field sites. The emissions from southern boreal stands varied as a function of stand age, fire weather conditions, ecozone, and soil moisture class. Sites affected by historical timber harvesting had greater combustion rates due to faster carbon stock recovery rates than sites recovering from wildfire events, indicating that different boreal forest land use practices can generate divergent carbon legacy effects. We estimate the 2015 fire season in Saskatchewan emitted a total of 36.3 ± 15.0 Tg C, emphasizing the importance of southern boreal fires for regional carbon budgets. Using the southern boreal as an analog, the northern boreal may undergo fundamental shifts in forest structure and carbon dynamics, becoming dominated by stands <70 years old that hold 2–7 kg C/m2less than current mature northern boreal stands. Our latitudinal approach reinforces previous studies showing that northern boreal stands are at a high risk of holding less carbon under changing disturbance conditions.
Climate change promotes transitions to tall evergreen vegetation in tropical Asia
Authors: Scheiter Simon , Kumar Dushyant , Corlett Richard T. , Gaillard Camille , Langan Liam , Lapuz Ralph Sedricke , Martens Carola , Pfeiffer Mirjam , Tomlinson Kyle W.
Published: June 2020

Vegetation in tropical Asia is highly diverse due to large environmental gradients and heterogeneity of landscapes. This biodiversity is threatened by intense land use and climate change. However, despite the rich biodiversity and the dense human population, tropical Asia is often underrepresented in global biodiversity assessments. Understanding how climate change influences the remaining areas of natural vegetation is therefore highly important for conservation planning. Here, we used the adaptive Dynamic Global Vegetation Model version 2 (aDGVM2) to simulate impacts of climate change and elevated CO2 on vegetation formations in tropical Asia for an ensemble of climate change scenarios. We used climate forcing from five different climate models for representative concentration pathways RCP4.5 and RCP8.5. We found that vegetation in tropical Asia will remain a carbon sink until 2099, and that vegetation biomass increases of up to 28% by 2099 are associated with transitions from small to tall woody vegetation and from deciduous to evergreen vegetation. Patterns of phenology were less responsive to climate change and elevated CO2 than biomes and biomass, indicating that the selection of variables and methods used to detect vegetation changes is crucial. Model simulations revealed substantial variation within the ensemble, both in biomass increases and in distributions of different biome types. Our results have important implications for management policy, because they suggest that large ensembles of climate models and scenarios are required to assess a wide range of potential future trajectories of vegetation change and to develop robust management plans. Furthermore, our results highlight open ecosystems with low tree cover as most threatened by climate change, indicating potential conflicts of interest between biodiversity conservation in open ecosystems and active afforestation to enhance carbon sequestration.
Dietary generalism accelerates arrival and persistence of coral‐reef fishes in their novel ranges under climate change
Authors: Monaco Cristián J. , Bradshaw Corey J. A. , Booth David J. , Gillanders Bronwyn M. , Schoeman David S. , Nagelkerken Ivan
Published: June 2020

Climate change is redistributing marine and terrestrial species globally. Life‐history traits mediate the ability of species to cope with novel environmental conditions, and can be used to gauge the potential redistribution of taxa facing the challenges of a changing climate. However, it is unclear whether the same traits are important across different stages of range shifts (arrival, population increase, persistence). To test which life‐history traits most mediate the process of range extension, we used a 16‐year dataset of 35 range‐extending coral‐reef fish species and quantified the importance of various traits on the arrival time (earliness) and degree of persistence (prevalence and patchiness) at higher latitudes. We show that traits predisposing species to shift their range more rapidly (large body size, broad latitudinal range, long dispersal duration) did not drive the early stages of redistribution. Instead, we found that as diet breadth increased, the initial arrival and establishment (prevalence and patchiness) of climate migrant species in temperate locations occurred earlier. While the initial incursion of range‐shifting species depends on traits associated with dispersal potential, subsequent establishment hinges more on a species’ ability to exploit novel food resources locally. These results highlight that generalist species that can best adapt to novel food sources might be most successful in a future ocean.
Climate change considerations are fundamental to management of deep‐sea resource extraction
Authors: Levin Lisa A. , Wei Chih‐Lin , Dunn Daniel C. , Amon Diva J. , Ashford Oliver S. , Cheung William W. L. , Colaço Ana , Dominguez‐Carrió Carlos , Escobar Elva G. , Harden‐Davies Harriet R. , Drazen Jeffrey C. , Ismail Khaira , Jones Daniel O. B. , Johnson David E. , Le Jennifer T. , Lejzerowicz Franck , Mitarai Satoshi , Morato Telmo , Mulsow Sandor , Snelgrove Paul V. R. , Sweetman Andrew K. , Yasuhara Moriaki
Published: June 2020

Climate change manifestation in the ocean, through warming, oxygen loss, increasing acidification, and changing particulate organic carbon flux (one metric of altered food supply), is projected to affect most deep‐ocean ecosystems concomitantly with increasing direct human disturbance. Climate drivers will alter deep‐sea biodiversity and associated ecosystem services, and may interact with disturbance from resource extraction activities or even climate geoengineering. We suggest that to ensure the effective management of increasing use of the deep ocean (e.g., for bottom fishing, oil and gas extraction, and deep‐seabed mining), environmental management and developing regulations must consider climate change. Strategic planning, impact assessment and monitoring, spatial management, application of the precautionary approach, and full‐cost accounting of extraction activities should embrace climate consciousness. Coupled climate and biological modeling approaches applied in the water and on the seafloor can help accomplish this goal. For example, Earth‐System Model projections of climate‐change parameters at the seafloor reveal heterogeneity in projected climate hazard and time of emergence (beyond natural variability) in regions targeted for deep‐seabed mining. Models that combine climate‐induced changes in ocean circulation with particle tracking predict altered transport of early life stages (larvae) under climate change. Habitat suitability models can help assess the consequences of altered larval dispersal, predict climate refugia, and identify vulnerable regions for multiple species under climate change. Engaging the deep observing community can support the necessary data provisioning to mainstream climate into the development of environmental management plans. To illustrate this approach, we focus on deep‐seabed mining and the International Seabed Authority, whose mandates include regulation of all mineral‐related activities in international waters and protecting the marine environment from the harmful effects of mining. However, achieving deep‐ocean sustainability under the UN Sustainable Development Goals will require integration of climate consideration across all policy sectors.
Parallel Simulation in Subsurface Hydrology: Evaluating the Performance of Modeling Computers
Authors: Sarris Theo S. , Scott David M. , Close Murray E.
Published: June 2020

Monte Carlo uncertainty analysis, model calibration and optimization applications in hydrology, usually involve a very large number of forward transient model solutions, often resulting in computational bottlenecks. Parallel processing can significantly reduce overall simulation time, benefiting from the architecture of modern computers. This work investigates system performance using two realistic flow and transport modeling scenarios, applied to various modeling hardware, to provide information on the expected performance of parallel simulations and inform investment decisions. We investigate how performance, measured in terms of speedup and efficiency, changes with increasing number of parallel processes. We conclude that the maximum performance achieved by parallelization can range from 40% to 100% of the theoretical limit, with the lower increases associated with multi‐CPU servers. The number of parallel processes required to maximize performance is application dependent, and in contrast to common practice, often needs to be significantly larger than the total number of system CPU cores. Further testing is required to better understand how the physical problem being simulated affects the optimal number of parallel processes needed. Finally, when laptops are considered for modeling applications, careful consideration should be given not only to the specifications but also to the intended use designated by the manufacturer.
Minimally invasive surgery for haemophilic pseudotumour of the limbs: 28 years of experience
Authors: Caviglia Horacio Alberto , Douglas Price Ana Laura , Cambiaggi Guillermo , Honorat Egle , Salgado Pablo , Galatro Gustavo Alberto
Published: June 2020

Introduction

Haemophilic pseudotumour (HP) is an encapsulated haematoma in patients with haemophilia (PWH) which has a tendency to progress and produce clinical symptoms related to its anatomical location.

Aim

To show the experience of one surgeon who has been using mini‐invasive technique to treat pseudotumours of limbs in PWH with and without inhibitors at one centre for 28 years.

Materials and Methods

Thirty‐three patients with 39 HP were treated. All patients had haemophilia A. Twenty‐four patients had no inhibitors (72.8%), and 9 had inhibitors (27.2%). The mean follow‐up was 16 years (1‐25). All patients had x‐rays and MRIs. All of them received Buenos Aires protocol as conservative treatment for 6 weeks. MRIs were repeated after 6 weeks’ treatment to assess response to treatment.

Surgery was performed in patients who did not respond to conservative treatment.

Results

After Buenos Aires protocol, four pseudotumours did not shrink (10.24%), 33 (84.61%) shrank, and two (5.12%) healed. Thirty‐seven pseudotumours had surgery, 35 pseudotumours (94.59%) healed with minimally invasive treatment, and two did not heal (5.41%).

No infection was observed with this treatment. The mortality rate for the series was 0%.

Conclusion

The minimally invasive treatment of pseudotumours was effective in 95% of the cases and resulted in no mortality in this series after 28 years.
Finding harmony within dissonance: Engaging patients, family/caregivers and service providers in research to fundamentally restructure relationships through integrative dynamics
Authors: Mulvale Gillian , Green Jenn , Miatello Ashleigh , Cassidy Ann E. , Martens Terry
Published: June 2020

Background

Deeply divided ideological positions challenge collaboration when engaging youth with mental disorders, caregivers and providers in mental health research. The integrative dynamics (ID) approach can restructure relationships and overcome ‘us vs them’ thinking.

Objective

To assess the extent to which an experience‐based co‐design (EBCD) approach to patient and family engagement in mental health research aligned with ID processes.

Methods

A retrospective case study of EBCD data in which transitional‐aged youth (n = 12), caregivers (n = 8) and providers (n = 10) co‐designed prototypes to improve transitions from child to adult services. Transcripts from focus groups and a co‐design event, co‐designed prototypes, the resulting model, evaluation interviews and author reflections were coded deductively based on core ID concepts, while allowing for emergent themes. Analysis was based on pattern matching. Triangulation across data sources, research team, and youth and caregiver reflections enhanced rigour.

Findings

The EBCD focus group discussions of touchpoints in experiences aligned with ID processes of acknowledging the past, by revealing the perceived identity mythos of each group, and allowing expression of and working through emotional pain. These ID processes were briefly revisited in the co‐design event, where the focus was on the remaining ID processes: building cross‐cutting connections and reconfiguring relationships. The staged EBCD approach may facilitate ID, by working within one's own perspective prior to all perspectives working together in co‐design.

Conclusion

Researchers can augment patient engagement approaches by applying ID principles with staged integration of groups to improve relations in mental health systems, and EBCD shows promise to operationalize this.
Engineering rheological response in chitosan–sophorolipid systems through controlled interactions
Authors: Pingali S. , Benhur A. M. , Amin S.
Published: June 2020

Objective

The purpose of this study was to understand the impact of the biopolymer chitosan on the rheological behaviour of the biosurfactant sophorolipid as well as the effects of ionization and electrolyte addition on the chitosan–sophorolipid system.

Methods

Rotation mechanical rheometry was used to study the rheological response of the chitosan–SL systems. Frequency sweeps were conducted to analyse the rheological properties of the system at low‐frequency ranges, and bulk viscosity of the system was studied at high shear rates for each sample.

Results

The biosurfactant sophorolipid on its own has very low viscosity. The bulk rheology results show that the addition of chitosan enhances the viscosity and viscoelastic properties of the chitosan–sophorolipid system indicating the presence of synergistic interactions between the two systems. Electrolyte addition had a significant impact on the system’s rheological response. Addition of salt built the viscosity of pure chitosan. However due to charge screening effects, it resulted in a decrease in viscosity for the chitosan–sophorolipid system. On further increasing the salt concentration, an increase in viscosity was observed but not beyond the value obtained for the chitosan–SL system without any salt. An increase in pH results in increased ionization of the carboxylic acid groups in acidic SL, which in turn enhances the synergistic interactions between chitosan and SL.

Conclusion

The strong charge interactions between chitosan and sophorolipid lead to formation of an integrated gel‐like network, thus building the viscosity of the system. A variation in parameters like biopolymer concentration, electrolyte and ionic strength has the potential to modify the bulk rheological properties of the chitosan–SL system.
Patterns of skin cancer and treatment outcomes for patients with albinism at Kisangani Clinic, Democratic Republic of Congo
Authors: Inena Gaylord , Chu Brian , Falay Dadi , Limengo Bambale , Matondo Ibanda , Bokanga Abisa , Kovarik Carrie , Williams Victoria L.
Published: June 2020

Background

People with albinism (PWA) are at increased risk of photodamage and skin cancer. In many parts of Africa, there is a significant lack of knowledge regarding albinism which can lead to societal stigma, discrimination, and persecution from an early age. In the Democratic Republic of Congo (DRC), there is limited clinical data on PWA and skin cancer. We aim to better understand sociodemographics, risk factors, clinical features, and outcomes of this population.

Methods

Patients with a diagnosis of albinism and skin cancer presenting to Kisangani Albino Clinic were enrolled.

Results

Of 205 PWA, 61 patients were diagnosed with skin cancer with a mean age of 26.5 years. Common occupations were student (45.6%) or unemployed (26.4%). Discrimination was experienced from close contacts (24.4%) and society (67.4%). A majority (88.5%) had never used sunscreen, only 4.9% used fully sun protective clothing, and 90.2% spent 4 or more hours in the sun daily. Skin cancers had a mean size of 3.8 cm and were most commonly located on the face (47.7%). Squamous cell carcinoma was the most common histopathological diagnosis. Most patients underwent excision, and 90.2% had clinical clearance of tumors at a mean follow‐up of 5.7 months.

Conclusion

People living with albinism in the DRC experience a high rate of nonmelanoma skin cancers at a young age and additionally face a number of psychosocial challenges. This study represents the first attempt to analyze a cohort of patients with albinism from the DRC and serves to increase awareness of this vulnerable population.
Effects of organizational commitment, job satisfaction and workplace violence on turnover intention of emergency nurses: A cross‐sectional study
Authors: Li Na , Zhang Lichuan , Xiao Guangqing , Chen Zhuo Job , Lu Qian
Published: June 2020

Aims

To describe turnover intention of emergency nurses and clarify the effects of organizational commitment, job satisfaction and workplace violence on turnover intention.

Background

Research has showed the predictors of turnover intention differed among nurses of different specialties. However, research on turnover intention has mostly focused on general nurses rather than emergency nurses.

Design

A descriptive, cross‐sectional study was conducted.

Methods

A self‐administered questionnaire was used to collect data from 415 emergency nurses in Beijing, China, using convenience sampling. Path analysis was used to test the relationships between organizational commitment, job satisfaction, workplace violence and turnover intention.

Results

Most emergency nurses (90.2%) had a high level or very high level of turnover intention. Contrary to previous studies, organizational commitment had a significant direct positive effect on workplace violence. It also had a direct positive effect on job satisfaction and a negative effect on turnover intention. Workplace violence had a negative effect on job satisfaction and a positive effect on turnover intention. Job satisfaction had a direct negative effect on turnover intention.

Conclusion

To reduce turnover intention in the emergency department, measures should be taken to reduce workplace violence and increase nurses' job satisfaction, especially those with high organizational commitment.