bluuebunny/crossref_metadata_2025 huggingface dataset:
A macrophage migration inhibitory factor as a predictor of reperfusion myocardial injury in patients with st-segment elevation myocardial infarction
Authors: Vishnevskaya I , Storozhenko T.Y.E , Kopytsya M.P
Published: November 2020

Introduction

Major adverse cardiovascular events in patients with ST-segment elevation myocardial infarction (STEMI) are still common despite the modern treatment approaches. It may be caused by the “no-reflow” phenomenon. One of the promising biomarkers for the coronary “no-reflow” phenomenon prediction is proinflammatory cytokine macrophage migration inhibitory factor (MIF).

Purpose

To estimate the role of MIF in the prediction of early reperfusion myocardial injury in patients with STEMI.

Methods

The study involved 341 STEMI patients (78.6% male and 21.4% female) with an average age of 59.08±9.65 years. Control group of 12 healthy volunteers included. All patients were made to undergo a baseline investigation. In addition, the level of MIF determined twice during the first 12 hours of STEMI, before the percutaneous coronary intervention (PCI) and after the procedure. Coronary blood flow evaluated using TIMI flow grade and myocardial blush grade (MBG). All patients had epicardial blood flow TIMI 3. The criteria for “no-reflow” diagnosis were myocardial perfusion at MBG 0 or MBG 1 level with complete recovery of epicardial blood flow or ST-segment resolution (rST) of less than 70% from baseline within 2 hours after PCI. All patients were divided into two groups according to MBG and rST after PCI more and less than 70%: 147 patients in the first group with MBG stage 0–1, 182 patients with MBG stage 2–3

Results

64% of STEMI patients had elevated MIF levels above the highest value in healthy controls (2778±217 ng/ml; 225±6,7 ng/ml; p=0,0003). The level of MIF biomarker, determined before PCI was significantly higher in the group of patients with MBG 0–1 in comparison to MBG 2–3. (4708±471 ng/ml vs 2914±347ng/ml; p=0,004). Using the multivariate regression analysis, the dependencies of the biomarker MIF on the parameters of the reperfusion myocardial injuries were obtained. MIF measured before revascularization as well as the patient's gender, was an independent predictor of MBG 0–1 and rST less than 70% (coefficients Beta 0,1; odd ratio 1,1; 95%confidential interval (CI) 1,0–1,2; p=0,037 and coefficient Beta 2,9; odd ratio 17.7; 95% CI 0,96–32; p=0,05, respectively).

Conclusions

The study revealed that MIF predicts reperfusion myocardial injury in patients with STEMI. Future investigations of the MIF biological effects are the perspective direction in the field of modern cardiology.

Funding Acknowledgement

Type of funding source: None
Obstructive respiratory events transiently impair electromechanical coupling and increase premature ventricular contraction rate in a drug-induced Long-QT-2 pig model
Authors: Linz B , Flethoj Madsen M , Hotbjerg Hansen M , Melis Hesselkilde E , Saljic A , Hohl M , Wirth K , Linz D , Sattler M , Tfelt-Hansen J , Jespersen T
Published: November 2020

Background

Obstructive sleep apnea (OSA) is characterized by intermittent negative thoracic pressure fluctuations and intermittent hypoxemic events. Recent findings associate OSA with impaired ventricular repolarization during sleep and increased risk of sudden cardiac death, which may have special implications for Long-QT-2-syndrome patients. Therefore, we elucidated changes in ventricular repolarization and electromechanical coupling (electromechanical window; EMW) during either obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) or hypoxemic events simulated by intermittent hypoxia (IH) in vehicle (VEH) and dofetilide (DOF) treated pigs, as a simulation of drug induced Long-QT-2 syndrome.

Methods

In sedated spontaneously breathing pigs, either VEH or DOF (50 μg/kg) was perfused and INAP was applied by a negative pressure device connected to the intubation tube. For IH-application the device was connected and left turned off. INAP or IH was maintained for 75 seconds followed by a ten-minute resting period. In order to evaluate the electromechanical window, the time difference between electrical (QT-duration) and mechanical systole (Q-wave to the end of left ventricular pressure signal, QLVPend) was measured before (pre-INAP/-IH), during and 60 seconds after INAP/IH (post-INAP/-IH). Incidence rates of premature ventricular contractions (PVC) and ventricular tachycardia were compared pre- to post-INAP/-IH.

Results

In VEH-pigs, EMW shortened throughout INAP and post-INAP periods steadily (VEH: pre-INAP: 81.69±2.31ms; INAP: 55.65±6.13ms; post-INAP: 38±8.89ms. p=0.008). EMW shortening during post-INAP was associated with an increase in PVCs (VEH: pre-INAP 5.41±1.87 vs. post-INAP 26.5±8.15; p=0.04). In DOF-pigs, INAP-associated EMW-shortening was further potentiated (DOF: pre-INAP: 61.16±7.18ms; INAP: 38.09±9.84ms; post-INAP: 14.93±9.24ms. p=0.016), which was associated with an increase in PVCs (DOF: pre-INAP 4.75±2.36 vs. post-INAP 36.58±10.92; p=0.017). Administration of Atenolol could prevent post-INAP shortening of the EMW and decrease counts of premature ventricular contractions. While desaturations were comparable in INAP and IH, IH did not result in EMW-shortening or increased arrhythmia risk.

Conclusion

Transient dissociation of the ventricular electromechanical coupling during a simulated obstructive apnea, but not during IH, creates a dynamic and sympathetically driven arrhythmogenic substrate. Apnea associated ventricular electromechanical uncoupling was aggravated in a drug-induced Long-QT-2 simulation. Whether OSA represents a modifiable arrhythmogenic risk factor in Long-QT-2-patients warrants further studies.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Novo nordisk fonden
Genetic variants in calcium regulatory cardiac genes and their contribution to Takotsubo syndrome
Authors: Treu F , Dybkova N , Jung P , Li Y , Huebscher D , Maurer W , Hasenfuss G , Voigt N , Sossalla S , Wollnik B , Streckfuss-Boemeke K
Published: November 2020

Background and purpose

Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction similar to a myocardial infarction (MI) in the absence of coronary artery stenosis. Patients show symptoms similar to the acute MI with increased biomarkers and blood serum catecholamines. Recently, we developed a patient-specific TTS stem cell model and identified a higher sensitivity to catecholamine-induced stress. Furthermore, familial TTS cases and genetic studies point to a genetic predisposition. The purpose of this study was to analyze a genetic predisposition by characterizing genetic variants in genes associated with cardiac pathologies and their impact on calcium homoeostasis in TTS.

Methods and results

Whole exome sequencing analysis of a TTS patient discovered 2 missense AHNAK variants in its C-terminal domain and in addition the missense variant F189L in the calcium buffering calsequestrin 2 gene (CASQ2). AHNAK is a 700kDa big nucleoprotein and is involved in the β-adrenergic regulation of the cardiac calcium channel Cav1.2. 3-month old TTS-iPSC-derived cardiomyocytes (CM) were generated and the variants were confirmed by sequencing. We found AHNAK higher expressed in TTS-iPSC-CMs compared to control, whereas no expression alteration was observed for Cav1.2. Since AHNAK is described to act as a repressor towards Cav1.2, which is relieved under β-adrenergic stimulation, we analyzed the effect of AHNAK variants on a potential co-localization and interaction between both proteins. AHNAK and Cav1.2 were shown to co-localize in the cytoplasm as well as the membranes and co-immunoprecipitation experiments confirmed an interaction of AHNAK and Cav1.2 in all tested control- and TTS-iPSC-CMs. On a functional level, we were able to show by patch clamp analysis that Cav1.2 calcium currents are significantly increased in TTS-iPSC-CMs compared to control. The influence of CASQ2-F189L on sarcomeric reticulum (SR) calcium load was analyzed by epifluorescence microscopy using FURA4 and caffeine-applications. We found significantly decreased SR calcium content with an increased fractional release during systole in TTS-iPSC-CMs. To test, whether these variants are the main reason for altered interaction of AHNAK and Cav1.2, calcium currents or SR calcium load in TTS need to be proven in the future by using CRISPR/Cas9-rescued AHNAK/CASQ2 lines.

Conclusion

Here we show the cardiac functional consequences of AHNAK and CASQ2 missense mutations in TTS-iPSC-CMs with regard to calcium currents and SR calcium load. These results show that AHNAK and CASQ2 variants may predispose to TTS and enable a new therapeutic option for TTS.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Else Kröner-Fresenius Foundation
Cyclin dependent kinase 1 (CDK1) positively regulates cardiac hypertrophy and fibrosis via TGF-beta pathway
Authors: Yamamoto T , Matsushima S , Okabe K , Ikeda S , Ishikita A , Enzan N , Sada M , Tsutsui Y , Miyake R , Tsutsui H
Published: November 2020

Background

Transforming growth factor beta (TGF-β) critically mediates cardiac fibrosis by transforming fibroblasts to myofibroblasts in pathological conditions. Cyclin dependent kinases (CDKs), cell cycle-regulating proteins, are known to be intimately involved in cardiac fibrosis. Among CDK isoforms, CDK1 is essential for cell cycle progression and cell division. It is reported some interphase CDKs such as CDK4 or CDK6 were involved in cardiac fibrosis, however, detailed mechanisms of cardiac fibrosis through CDK1 and its interactions with TGF-β in cardiac fibrotic process haven't been elucidated. We hypothesize that CDK1 is involved in cardiac fibrotic process via TGF-β pathway and its suppression decreases TGF-β expression and transformation to myofibroblasts from fibroblasts presenting antifibrotic effect.

Methods and results

Isolated neonatal rat cardiac fibroblasts were treated with angiotensin II (ANG II, 1 μM, 24 h) or phosphate-buffered saline (PBS). ANG II increased CDK1 and TGF-β in cardiac fibroblasts, by 97% and 292%, respectively (p<0.05). Administration of Ro-3306, a specific CDK1 inhibitor (1 μM, 24 h), suppressed TGF-β protein levels in ANG II-treated cardiac fibroblasts by 58% (p<0.05). Similarly, knockdown of CDK1 by RNA silencing also inhibited ANG II-induced increases in TGF-β in cardiac fibroblasts by 39% (p<0.05). ANG II increased alpha-smooth muscle actin (α-SMA), which is a marker of myofibroblasts, and knockdown of CDK1 significantly suppressed it by 49% (p<0.05). In vivo study, 11-week-old male C57BL/6J mice were administered ANG II continuously with infusion pump, at a dose of 1000 ng/kg/min, for a week. Also, Ro-3306 was intraperitoneally injected at a dose of 2 mg/kg/day, every other day, for a week. First, Ro-3306 attenuated ANG II-mediated cardiac hypertrophy indicated by heart weight and echocardiographic parameter as to left ventricular wall thickness. Second, CDK1 and TGF-β expression were significantly augmented in ANG II-infused mice by 404% and 113%, respectively (p<0.05). Injection of Ro-3306 suppressed TGF-β protein levels by 48%, although the difference wasn't statistically significant (p=0.09). Finally, histopathological examination (Masson's trichrome stain) demonstrated remarkable repression of ANG II-induced cardiac fibrosis by Ro-3306.

Conclusions

CDK1 positively controls cardiac fibrotic process by regulating transformation to cardiac myofibroblasts from fibroblasts via TGF-β pathway. It also presents an antihypertrophic effect on ANG II stimulation. CDK1 is a potential therapeutic target of cardiac fibrosis and hypertrophy.

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): KAKENHI
Distinct dietary alpha-linolenic acid-dependent shifts in the fecal microbiome composition suppresses aging-associated inflammatory responses and thrombus formation
Authors: Saeedi Saravi S.S , Bonetti N.R , Camici G.G , Luscher T.F , Beer J.H
Published: November 2020

Background

Aging is associated with alterations in the fecal microbiome composition. The microbiota-derived trimethylamine-N-oxide (TMAO) correlates with arterial thrombotic events, e.g. myocardial infarction and stroke, the leading causes of mortality worldwide. The omega-3 fatty acid (n-3 FA) α-linolenic acid (ALA) has been shown to be protective against thrombosis and associated pathologies. Therefore, we hypothesized that long-term dietary ALA supplementation protects against the aging-associated microbiome dysbiosis, and reduces inflammatory and thrombotic responses.

Methods

24 week-old male C57BL/6 mice were fed either a high ALA (7.3g%) or low ALA (0.03g%) diet for 12 months. We examined the compositional changes of fecal microbiota of the animals treated with high vs. low ALA via 16S rRNA gene sequencing. The plasma levels of TMAO and its precursors choline and betaine, and LPS were measured by ELISA. Additionally, the platelet aggregation in response to thrombin, and thrombus formation on collagen under high-shear flow conditions of 3000/sec (to mimic blood flow in stenosed arteries) were investigated.

Results

Genomic analyses showed that the abundance of Phylum Proteobacteria and the family of desulfovibrio were reduced 71.72% and 51.73% in the aged high ALA-treated mice (p<0.01 and p<0.001, resp.) that may result in decrease in TAMO production and the subsequent inflammatory responses. However, microbial diversity of Bacteroidetes or Fermicutes and Bacteroidetes/Fermicutes ratio did not demonstrate a significant change between high vs. low ALA groups. Interestingly, the dietary intake of high ALA increased the abundance of Lachnospiraceae (p<0.01) that may exert anti-inflammatory effects. Importantly, high ALA significantly decreased the plasma levels of TMAO (p<0.01) and its precursor choline (P<0.05), but not betaine. The pro-inflammatory cytokine TNF-α showed a significant reduction (p<0.05), whereas plasma IL-1β did not change significantly following high ALA supplementation. An increased thrombus formation on collagen under high-shear flow (36.34%, p<0.01) and thrombin-induced platelet aggregation (31.31%, p<0.05) were found in the aged mice.

Conclusion

These studies demonstrate that an ALA-rich diet induces beneficial bacterial shifts in the aging-associated fecal microbiome that may lead to the suppression of inflammatory and thrombotic responses. Hence, long-term dietary ALA supplementation may be exploited as a nutritional antithrombotic strategy in the aging.

Microbiome-Thrombosis-Aging

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Swiss National Science Foundation (SNSF)
Impact of hypoxia on immune cells in human atherosclerotic plaques
Authors: Vorobyeva D , Lebedeva A , Elizarova A , Maryukhnich E , Gontarenko V , Shpektor A , Margolis L.B , Vasilieva E
Published: November 2020

Background

Inflammation plays a major role in atherosclerotic plaques' progression and was shown to be associated with the formation of hypoxic areas within the plaques. However, the data about the impact of hypoxia on atherosclerosis are contradictory, in part due to inadequacy of in vitro and animal models to reproduce faithfully the complexity of human atherosclerotic plaques.

Purpose

The aim of this study was to investigate the effect of hypoxia on immune status in the ex vivo system of human atherosclerotic plaques.

Methods

We collected 25 atherosclerotic plaques from patients undergoing carotid endarterectomy, cut plaques into ring-shaped slices and cultured them for 24 hours at the liquid/air interface on collagen sponges under hypoxic (2% O2) and normoxic (12% O2) conditions. After 24 hours we evaluated T-cell activation status within plaques according to the presence of membrane activation markers by means of multiparametric flow cytometry and the activity of cytokine production using xMAP technology.

Results

We found that CD8 T cells from human atherosclerotic plaques cultured under hypoxic conditions compared to normoxic conditions have a decreased expression of CD69 activation marker (42.7 [34.3; 50.9]% vs 53.8 [33.3; 63.3]%, n=10, p=0.047) and lower level of CD69 and HLA-DR coexpression (16.0 [10.5; 22.3] vs 22.6 [11.3; 28.2], n=10, p=0.02). CD4 T cells did not show any significant changes in expression of activation markers under hypoxia. Hypoxic conditions also resulted in a reduced IL-10 production (104.2 [53.8; 170.9] vs 235.2 [158.5; 335.3] pg/100 mg of tissue, n=20, p=0.0001) and increased VEGF production (116.1 [79.8; 253.5] vs 89.9 [71.1; 148.8] pg/100 mg of tissue, n=20, p=0.033).

Conclusions

Our results indicate that hypoxia causes a decrease in the activity of cytotoxic T cells and increases stimuli for angiogenesis within the human atherosclerotic plaques. The established ex vivo model of human atherosclerotic plaques culture under hypoxia enables further studies of the hypoxia impact on atherosclerosis.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Russian Science Foundation grant
Identification of mRNA and microRNA profiles in right ventricular dysfunction induced type II cardiorenal syndrome
Authors: Chen K.T , Liao Y.L
Published: November 2020

Background

Type II Cardiorenal syndrome (CRS) induced by right ventricular (RV) dysfunction is a disease with high mortality but little attention. Its unique pathophysiology and molecular characteristics remains puzzled. This study is aimed to investigate the transcriptomic expression profile of circRNAs, miRNAs and mRNAs, and identify the potential therapeutic targets that regulate molecular signaling networks in RV dysfunction-induced type II CRS.

Methods

Male C57BL/6 mice receiving pulmonary artery constriction were used to establish RV dysfunction model. The expression profiles of mRNAs, miRNAs and circRNAs in RV and kidney tissues were obtained by whole transcriptome sequencing. Bioinformatics analyses were performed, including Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and co-expression network analysis. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to confirm the results of transcriptome sequencing.

Findings

A total of 741 and 86 differentially expressed (DE) mRNAs, 159 and 29 DEmiRNAs and 233 and 104 DEcircRNAs were found in RV and kidney tissue, respectively. Pairs of miRNA-mRNA were established. GO and KEGG analysis displayed a significant correlation with proliferation signaling pathways and metabolic pathways. Then the circRNA-miRNA-mRNA network related to proliferation and metabolic pathways were established. We identified hub circRNA-miRNA-mRNA pairs affected the fibrotic, proliferative and metabolic pathways significantly.

Interpretation

These findings indicate that the function of ceRNA networks play an important role in RV dysfunction induced type II CRS. Therefore, these circRNA-miRNA-mRNA pairs should be potential targets for treatment of this disease.

Figure 1

Funding Acknowledgement

Type of funding source: None
Clot formation, lysis and ultrastructure in patients with acute phase myocardial infarction
Authors: Siniarski A , Baker S.R , Duval C , Gajos G , Nessler J , Ariens R.A.S
Published: November 2020

Background/Introduction

Patients with established coronary artery disease have impaired clot structure and lysis. Prior research has compared patients with myocardial infarction to those with stable coronary artery disease (without a healthy reference), or patients after myocardial ischemia. The role of clot structure in the acute phase of the disease is unknown.

Purpose

Investigate clot structure in the acute phase of myocardial infarction (AMI) compared to healthy controls.

Methods

Plasma clots from AMI patients (within 12 hours of symptoms onset) or healthy controls were analyzed by turbidity and lysis. Clot pore size was determined by permeation. Clot ultrastructure was determined by confocal and scanning electron microscopy. Average fiber radius and protofibril packing were investigated by turbidimetry.

Results

Analysis on clot formation, using turbidity, showed increased lag time (24%, p<0.05), suggesting changes in protofibril packing and increased fiber size for AMI patients compared to controls. Additionally, AMI clots formed more quickly as evidenced by average rate of clotting (2.9-fold increase, p<0.001) and time to maximum absorbance (38% decrease, p<0.0001). Decreased plasminogen in AMI patients (23%, p<0.05) had strong effects on clot lysis, including increased time to half lysis (1.72-fold, p<0.0001) and increased time to maximum lysis rate (7.96-fold, p<0.0001). Taken together, these results suggest that AMI patients form less porous clots made from densely packed fibers with decreased numbers of protofibrils, which was confirmed using permeation (1.05-fold decrease, p<0.0001), confocal (Figure 1) and scanning electron microscopy (46% increase, p<0.0001), and turbidimetry (16% decrease, p<0.05) respectively.

Conclusions

Plasma from patients with AMI form denser and less permeable clots that lyse more slowly than healthy controls. These data show marked abnormalities in clot ultrastructure that contribute to the high risk of thrombosis during the acute phase of myocardial infarction, which has not shown in previous investigations.

Figure 1. Confocal microscopy of AMI vs. controls

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Jagiellonian University Medical College to G.G. (N41/DBS/000096) and BHF Programme Grant to S.R.B. and R.A.S.A. (RG/18/11/34036).
Deep learning and the electrocardiogram: review of the current state-of-the-art
Authors: Somani Sulaiman , Russak Adam J , Richter Felix , Zhao Shan , Vaid Akhil , Chaudhry Fayzan , De Freitas Jessica K , Naik Nidhi , Miotto Riccardo , Nadkarni Girish N , Narula Jagat , Argulian Edgar , Glicksberg Benjamin S
Published: November 2020

In the recent decade, deep learning, a subset of artificial intelligence and machine learning, has been used to identify patterns in big healthcare datasets for disease phenotyping, event predictions, and complex decision making. Public datasets for electrocardiograms (ECGs) have existed since the 1980s and have been used for very specific tasks in cardiology, such as arrhythmia, ischemia, and cardiomyopathy detection. Recently, private institutions have begun curating large ECG databases that are orders of magnitude larger than the public databases for ingestion by deep learning models. These efforts have demonstrated not only improved performance and generalizability in these aforementioned tasks but also application to novel clinical scenarios. This review focuses on orienting the clinician towards fundamental tenets of deep learning, state-of-the-art prior to its use for ECG analysis, and current applications of deep learning on ECGs, as well as their limitations and future areas of improvement.
Reliability and validity of the Spanish (Spain) version of the consultation and relational empathy measure in primary care
Authors: García del Barrio Loreto , Rodríguez-Díez Cristina , Martín-Lanas Raquel , Costa Patricio , Costa Manual J , Díez Nieves
Published: November 2020

Background

Empathy is an essential competence in the medical field. There are no validated patient-rated empathy measures in Spanish (Spain). The Consultation and Relational Empathy (CARE) measure is a widely used patient-rated measure of physician empathy.

Objective

To analyse the reliability and validity of the Spanish (Spain) version of the CARE measure in primary care.

Methods

After translation, back translation and pilot testing, a convenient sample of 369 patients recruited through 21 primary care physicians in five primary care centres in Pamplona (Navarre, Spain) completed the Spanish (Spain) CARE (Sp-CARE) measure. The number of ‘does not apply’ or blank responses was calculated to assess acceptability. We analysed internal reliability by means of Cronbach’s alpha and ordinal alpha and homogeneity with corrected item-total correlations. The construct validity was examined by confirmatory factor analysis (CFA) and concurrent validity by Spearman’s correlation.

Results

We observed high acceptability; only 37 (1%) responses were marked ‘does not apply’ and only 3 (0.08%) were left blank. Cronbach’s alpha and ordinal alpha for the Sp-CARE measure were 0.953 and 0.970, respectively, and all corrected item-total correlations exceeded the accepted cut of 0.30, demonstrating high internal reliability and homogeneity. CFA corroborated the one-factor structure proposed in the original version. The Sp-CARE measure total score was significantly correlated with overall patient satisfaction (Spearman’s rho 0.45, P < 0.001).

Conclusion

The results support the reliability and validity of the Sp-CARE measure as a patient-rated empathy measure in the primary care setting.
The biology of thermoacidophilic archaea from the order Sulfolobales
Authors: Lewis April M , Recalde Alejandra , Bräsen Christopher , Counts James A , Nussbaum Phillip , Bost Jan , Schocke Larissa , Shen Lu , Willard Daniel J , Quax Tessa E F , Peeters Eveline , Siebers Bettina , Albers Sonja-Verena , Kelly Robert M
Published: November 2020

Thermoacidophilic archaea belonging to the order Sulfolobales thrive in extreme biotopes, such as sulfuric hot springs and ore deposits. These microorganisms have been model systems for understanding life in extreme environments, as well as for probing the evolution of both molecular genetic processes and central metabolic pathways. Thermoacidophiles, such as the Sulfolobales, use typical microbial responses to persist in hot acid (e.g. motility, stress response, biofilm formation), albeit with some unusual twists. They also exhibit unique physiological features, including iron and sulfur chemolithoautotrophy, that differentiate them from much of the microbial world. Although first discovered >50 years ago, it was not until recently that genome sequence data and facile genetic tools have been developed for species in the Sulfolobales. These advances have not only opened up ways to further probe novel features of these microbes but also paved the way for their potential biotechnological applications. Discussed here are the nuances of the thermoacidophilic lifestyle of the Sulfolobales, including their evolutionary placement, cell biology, survival strategies, genetic tools, metabolic processes and physiological attributes together with how these characteristics make thermoacidophiles ideal platforms for specialized industrial processes.
Genomics of Recombination Rate Variation in Temperature-EvolvedDrosophila melanogasterPopulations
Authors: Winbush Ari , Singh Nadia D
Published: November 2020

Meiotic recombination is a critical process that ensures proper segregation of chromosome homologs through DNA double-strand break repair mechanisms. Rates of recombination are highly variable among various taxa, within species, and within genomes with far-reaching evolutionary and genomic consequences. The genetic basis of recombination rate variation is therefore crucial in the study of evolutionary biology but remains poorly understood. In this study, we took advantage of a set of experimental temperature-evolved populations of Drosophila melanogaster with heritable differences in recombination rates depending on the temperature regime in which they evolved. We performed whole-genome sequencing and identified several chromosomal regions that appear to be divergent depending on temperature regime. In addition, we identify a set of single-nucleotide polymorphisms and associated genes with significant differences in allele frequency when the different temperature populations are compared. Further refinement of these gene candidates emphasizing those expressed in the ovary and associated with DNA binding reveals numerous potential candidate genes such as Hr38, EcR, and mamo responsible for observed differences in recombination rates in these experimental evolution lines thus providing insight into the genetic basis of recombination rate variation.
Majority of alpha2,6-sialylated glycans in the adult mouse brain exist inO-glycans: SALSA-MS analysis for knockout mice of alpha2,6-sialyltransferase genes
Authors: Ohmi Yuhsuke , Nishikaze Takashi , Kitaura Yoko , Ito Takako , Yamamoto Satoko , Sugiyama Fumihiro , Matsuyama Makoto , Takahashi Yoshimasa , Takeda Akira , Kawahara Toshio , Okajima Tetsuya , Furukawa Keiko , Furukawa Koichi
Published: November 2020

Sialic acids are unique sugars with negative charge and exert various biological functions such as regulation of immune systems, maintenance of nerve tissues and expression of malignant properties of cancers. Alpha 2,6 sialylated N-glycans, one of representative sialylation forms, are synthesized by St6gal1 or St6gal2 gene products in humans and mice. Previously, it has been reported that St6gal1 gene is ubiquitously expressed in almost all tissues. On the other hand, St6gal2 gene is expressed mainly in the embryonic and perinatal stages of brain tissues. However, roles of St6gal2 gene have not been clarified. Expression profiles of N-glycans with terminal α2,6 sialic acid generated by St6gal gene products in the brain have never been directly studied. Using conventional lectin blotting and novel sialic acid linkage-specific alkylamidationmass spectrometry method (SALSA-MS), we investigated the function and expression of St6gal genes and profiles of their products in the adult mouse brain by establishing KO mice lacking St6gal1 gene, St6gal2 gene, or both of them (double knockout). Consequently, α2,6-sialylated N-glycans were scarcely detected in adult mouse brain tissues, and a majority of α2,6-sialylated glycans found in the mouse brain were O-linked glycans. The majority of these α2,6-sialylated O-glycans were shown to be disialyl-T antigen and sialyl-(6)T antigen by mass spectrometry analysis. Moreover, it was revealed that a few α2,6-sialylated N-glycans were produced by the action of St6gal1 gene, despite both St6gal1 and St6gal2 genes being expressed in the adult mouse brain. In the future, where and how sialylated O-linked glycoproteins function in the brain tissue remains to be clarified.
Association Between Fatty Liver and Cirrhosis, Hepatocellular Carcinoma, and Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B
Authors: Li Jie , Yang Hwai-I , Yeh Ming-Lun , Le Michael H , Le An K , Yeo Yee Hui , Dai Chia-Yen , Barnett Scott , Zhang Jian Q , Huang Jee-Fu , Trinh Huy N , Wong Christopher , Wong Clifford , Hoang Joseph K , Cheung Ramsey , Yu Ming-Lung , Nguyen Mindie H
Published: November 2020

Background

Chronic hepatitis B (CHB) and fatty liver (FL) are common, natural history data on concurrent FL and CHB (FL-CHB) are limited. This study aimed to evaluate the effect of FL on cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) seroclearance incidence in CHB patients.

Methods

In a retrospective cohort study of 6786 adult CHB patients, we used propensity score matching (PSM) to balance the FL-CHB and non-FL CHB groups. Kaplan-Meier methods were used to compare cumulative cirrhosis, HCC, and HBsAg seroclearance rates between subgroups.

Results

Before PSM, compared to non-FL CHB, FL-CHB patients had lower 10-year cumulative rates of cirrhosis, HCC, and a higher HBsAg seroclearance rate. Similar results were found in the matched FL-CHB and non-FL CHB patients, as well as in the antiviral-treated PSM cohort. Cox proportional hazards model indicated FL to remain significantly and strongly associated with lower risk of cirrhosis and HCC (hazard ratio [HR], 0.19 [95% confidence interval {CI}, .12–.33], P < .001 and HR, 0.21 [95% CI, .09–.51], P = .001, respectively) in antiviral-treated patients but not in untreated patients.

Conclusions

FL was significantly associated with lower cirrhosis and HCC risk and higher HBsAg seroclearance. Further studies are needed to confirm our funding and investigate the mechanisms underlying the impact of FL on CHB.
Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients
Authors: Lersy François , Benotmane Ilies , Helms Julie , Collange Olivier , Schenck Maleka , Brisset Jean-Christophe , Chammas Agathe , Willaume Thibault , Lefebvre Nicolas , Solis Morgane , Hansmann Yves , Fabacher Thibaut , Caillard Sophie , Mertes Paul Michel , Pottecher Julien , Schneider Francis , Meziani Ferhat , Fafi-Kremer Samira , Kremer Stéphane
Published: November 2020

Background

Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings.

Methods

The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed.

Results

Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%).

Conclusions

Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.
Administrative Review Provisions in Chinese Investment Treaties: ‘Gilding the Lily’?
Authors: Chi Manjiao , Li Zongyao
Published: November 2020

Despite the popularization of investor-state arbitration (ISA), administrative review remains a helpful local remedy for investment-state dispute settlement (ISDS) in some states. China has a complicated and comprehensive legal system of administrative review. It has concluded a large number of international investment agreements (IIAs), and nearly half of them contain an administrative review provision. These provisions could be considered as an expropriation review mechanism, a standalone ISDS option, an ISA supporting measure or a pre-ISA requirement. Given that administrative review has legal and practical limits, and that China’s national law on dispute settlement and foreign investment governance keeps changing, the attractiveness and significance of administrative review for ISDS are diminishing. In China’s recent IIA-making, there appears an emerging trend of abandoning administrative review. In the long run, it remains to be seen how China will balance local remedies and ISA in IIA-making and foreign investment governance in the future.
Severe Acute Respiratory Syndrome-Coronavirus-2 Transmission in an Urban Community: The Role of Children and Household Contacts
Authors: Pitman-Hunt Chaya , Leja Jacqueline , Jiwani Zahra M , Rondot Dominique , Ang Jocelyn , Kannikeswaran Nirupama
Published: November 2020

This is a single-center US retrospective study of infection patterns among household sick contacts (HHSCs) of children with confirmed severe acute respiratory syndrome-coronavirus-2 infection in an urban setting. An HHSC was identified in fewer than half (42%) of the patients, and no child-to-adult transmission was identified.

This is a single center US retrospective study of infection patterns among household sick contacts of children with confirmed SARS-CoV-2 infection. A household sick contact was identified in fewer than half (42%) of patients and no child-to-adult transmission was identified.
Fracture and embolization of an implantable venous access device in patient with atrial septal defect
Authors: Syltern Julie , Jørgensen Geir , Norstein Jarle , Augestad Knut Magne
Published: November 2020

Totally implantable venous access devices (TIVADs) are frequently used for the administration of chemotherapy or parenteral nutrition and have proved to be safe and improve patient quality of life during treatment. Catheter-related infections are the most common complication, whereas catheter fracture and embolization is rarely seen. We present a case of a 61-year-old cancer patient in which the TIVAD fractured and embolized to the patient’s left knee 18 months after its initial placement. An endovascular procedure with intraoperative imaging revealed that the catheter had embolized to the popliteal artery and was successfully removed, the only explanation being the presence of an atrial septal defect. A bubble echocardiogram was unsuccessful in confirming the diagnosis. The catheter fracture could be related to an intravascular procedure that was performed 18 months prior to remove fibrin sheaths as a cause of port malfunction, or it could be a case of pinch-off syndrome.
Conceptualizing Youth Mental Health Through a Dual-Factor Model
Authors: Suldo Shannon M. , Doll Beth
Published: November 2020

This chapter summarizes evidence for the dual-factor model of mental health in which youth psychopathology and well-being are related but distinct and the promotion of wellness is equally important as amelioration of emotional and behavioral problems. The dual-factor model identifies 2 groups described in traditional mental health frameworks: youth without psychopathology who report positive emotional well-being (complete mental health) and youth who experience both psychopathology and low emotional well-being (troubled). Additional groups identified in dual-factor models are youth who are languishing emotionally but evidence no psychopathology (vulnerable) and youth who experience psychopathology while also evidencing emotional wellness (symptomatic but content). The use of the dual-factor model in school mental health facilitates identification of students who are vulnerable or symptomatic but content and need supports to foster positive emotions or manage distressing symptoms of disorders, as well as those who are troubled and need high-intensity or individualized mental health services.
Building Culturally Responsive Schools
Authors: Jones Janine , Miranda Antoinette Halsell
Published: November 2020

Public education in the United States is built on an unstable foundation of educational inequity. Educational achievement gaps, disproportionate discipline, and fiscal disinvestment all affect the socioemotional health of youth in schools. School reform efforts must include building the socioemotional well-being of students while also targeting systems-level change. Further, a comprehensive approach that attacks multiple problems of practice simultaneously as symptoms of a systemic problem is needed. In a culturally responsive school, personnel hold in constant an awareness the existence of educational inequity; they intentionally work toward for systems level change and support the needs of the whole child. This chapter presents a comprehensive method of facilitating systems level change that is holistically addressing the school context while also supporting the whole child. Building on the five tenets of the whole child approach, the chapter provides practical recommendations for implementation while building a culturally responsive school.
Building Family–School Partnerships to Support Positive Parenting and Promote Healthy Families
Authors: Garbacz S. Andrew , Mendez Linda M. Raffaele
Published: November 2020

The purpose of this chapter is to describe how family–school partnerships can support positive parenting practices and promote healthy families. Theoretical underpinnings of family–school partnerships are reviewed, which convey foundational elements for understanding family–school partnerships as well as a framework that can be used to adopt and implement family–school partnership interventions in schools. Next, research support for family–school partnerships is described, research that suggests the impacts of family–school partnerships as well as the mechanisms through which they effect change. The multitiered systems of support framework is invoked as an approach that can guide identifying and implementing relevant family–school partnership interventions in schools. Examples of family–school partnership interventions are described, practical guidance is offered, and key issues in adopting and implementing family–school partnership interventions are provided.
Promoting Physical Activity, Nutrition, and Sleep
Authors: Schmidt Ellyn M. , Hamilton Tessa N. , Hoffman Jessica A.
Published: November 2020

Children’s physical and mental health are impacted by keystone behaviors including eating, physical activity, and sleep. Schools represent a critical venue for health promotion, and school-based mental health professionals possess the knowledge and skills to implement prevention and intervention strategies while also guarding against unhealthy weight control behaviors. This chapter discusses strategies for promoting physical activity and healthy eating in schools, as well as approaches for promoting sufficient sleep. There is an emphasis on universal (i.e., Tier 1) strategies with some attention devoted to targeted (i.e., Tier 2) approaches. Two important themes in this chapter include (a) the importance of systems level changes that appropriately recognize that factors outside children’s control impact their ability to engage in healthy behaviors and (b) the value of family–school partnerships to promote physical activity, healthy eating, and sufficient sleep.
Promoting Students’ Positive Emotions, Character, and Purpose
Authors: Suldo Shannon M. , Mariano Jenni Menon , Gilfix Hannah
Published: November 2020

Grounded in positive psychology, this chapter focuses on constructs that increase well-being and may result in a flourishing emotional state. Within the PERMA framework, flourishing is reflected in positive emotions, engagement, relationships, meaning, and accomplishment. Specifically, this chapter takes an in-depth look into the constructs of positive emotions, character, and purpose. Information on measurement tools, correlates, and possible interventions for each of the three constructs is provided. An emphasis is also placed on promising positive psychology interventions, many of which utilize strategies involving character strengths as defined in accordance with the Values in Action (VIA) Classification of Character Strengths and Virtues. The chapter concludes with information on how a reader can implement various positive psychology activities, as well as different school based-programs that incorporate purpose and positive psychology interventions.
Afterword
Authors: Lazarus Philip J. , Cash Ralph Eugene
Published: November 2020

In this afterword, the authors emphasize that all school-based mental health providers must be advocates for the emotional well-being of our youth. They emphasize that advocates are made, not born, and discuss specific knowledge and skills necessary for effective advocacy. They then discuss three top advocacy priorities: (a) increasing the number of mental health professionals in the schools; (b) promoting programs, policies, training, and research that supports the emotional well-being of youth; and (c) supporting models, frameworks, and positions developed by the National Association of School Psychologists, the American Psychological Association, and many other mental health associations that support children’s needs. In closing, they discuss how to be advocates for all children and, most important, our most vulnerable student populations at the personal, local (including school), state, national, and international levels.
Background and CIT-S Overview
Authors: Mamani Amy Weisman de , McLaughlin Merranda , Altamirano Olivia , Lopez Daisy , Ahmad Salman Shaheen
Published: November 2020

Chapter 2 describes the foundational research from which it is based and introduces the main outline and goals of culturally informed therapy for schizophrenia (CIT-S). The chapter begins by introducing the history of family therapy for people with schizophrenia, its empirical support, and the cultural gaps that limited its generalizability in early clinical trials. Notable predictors of wellness (e.g., expressed emotion, collectivism, religion/spirituality, and ethnic pride) are reviewed, and relevant cultural differences are explored. The research reviewed provides the framework for the five modules of CIT-S (family collectivism, psychoeducation, spirituality, communication training, and problem-solving) and its session structure. Clinicians are encouraged to not only build their own knowledge of culture, history, and religion/philosophy but also to recognize the unique variance within each family and to be open to the varied intersecting identities that will influence and provide richness to their sessions.
Module 4—Communication Training (Sessions 10–12)
Authors: Mamani Amy Weisman de , McLaughlin Merranda , Altamirano Olivia , Lopez Daisy , Ahmad Salman Shaheen
Published: November 2020

This chapter introduces the Communication Training Module, which is aimed at improving communication patterns amongst family members in ways that prioritize their values and culture. The chapter reviews the role of communication in mental health, communication deviance within schizophrenia spectrum disorders, and notable cultural differences in communication styles. The communication module is then introduced, including key components of communication (i.e., the three Cs: clear, concise, and confirming what you hear) and guidelines for facilitating roleplays. Clinicians are instructed on how to discuss communication and culture with their clients and how to introduce multiple communication strategies through homework assignments and worksheets. Strategies such as expressing positive feelings, attentive listening, making positive requests for change, and expressing negative feelings about a specific behavior are included. A case illustration about two Black mothers and their son with schizophrenia demonstrates the process.