bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammation as A Precursor of Atherothrombosis, Diabetes and Early Vascular Aging
Authors: Barbu Elena , Popescu Mihaela-Roxana , Popescu Andreea-Catarina , Balanescu Serban-Mihai
Published: January 2022

Vascular disease was for a long time considered a disease of the old age, but it is becoming increasingly clear that a cumulus of factors can cause early vascular aging (EVA). Inflammation plays a key role in vascular stiffening and also in other pathologies that induce vascular damage. There is a known and confirmed connection between inflammation and atherosclerosis. However, it has taken a long time to prove the beneficial effects of anti-inflammatory drugs on cardiovascular events. Diabetes can be both a product of inflammation and a cofactor implicated in the progression of vascular disease. When diabetes and inflammation are accompanied by obesity, this ominous trifecta leads to an increased incidence of atherothrombotic events. Research into earlier stages of vascular disease, and documentation of vulnerability to premature vascular disease, might be the key to success in preventing clinical events. Modulation of inflammation, combined with strict control of classical cardiovascular risk factors, seems to be the winning recipe. Identification of population subsets with a successful vascular aging (supernormal vascular aging—SUPERNOVA) pattern could also bring forth novel therapeutic interventions.
From Genome Sequencing to CRISPR-Based Genome Editing for Climate-Resilient Forest Trees
Authors: Cao Hieu Xuan , Vu Giang Thi Ha , Gailing Oliver
Published: January 2022

Due to the economic and ecological importance of forest trees, modern breeding and genetic manipulation of forest trees have become increasingly prevalent. The CRISPR-based technology provides a versatile, powerful, and widely accepted tool for analyzing gene function and precise genetic modification in virtually any species but remains largely unexplored in forest species. Rapidly accumulating genetic and genomic resources for forest trees enabled the identification of numerous genes and biological processes that are associated with important traits such as wood quality, drought, or pest resistance, facilitating the selection of suitable gene editing targets. Here, we introduce and discuss the latest progress, opportunities, and challenges of genome sequencing and editing for improving forest sustainability.
Engineering of Injectable Antibiotic-laden Fibrous Microparticles Gelatin Methacryloyl Hydrogel for Endodontic Infection Ablation
Authors: Ribeiro Juliana S. , Münchow Eliseu A. , Bordini Ester A. F. , Rodrigues Nathalie S. , Dubey Nileshkumar , Sasaki Hajime , Fenno John C. , Schwendeman Steven , Bottino Marco C.
Published: January 2022

This study aimed at engineering cytocompatible and injectable antibiotic-laden fibrous microparticles gelatin methacryloyl (GelMA) hydrogels for endodontic infection ablation. Clindamycin (CLIN) or metronidazole (MET) was added to a polymer solution and electrospun into fibrous mats, which were processed via cryomilling to obtain CLIN- or MET-laden fibrous microparticles. Then, GelMA was modified with CLIN- or MET-laden microparticles or by using equal amounts of each set of fibrous microparticles. Morphological characterization of electrospun fibers and cryomilled particles was performed via scanning electron microscopy (SEM). The experimental hydrogels were further examined for swelling, degradation, and toxicity to dental stem cells, as well as antimicrobial action against endodontic pathogens (agar diffusion) and biofilm inhibition, evaluated both quantitatively (CFU/mL) and qualitatively via confocal laser scanning microscopy (CLSM) and SEM. Data were analyzed using ANOVA and Tukey’s test (α = 0.05). The modification of GelMA with antibiotic-laden fibrous microparticles increased the hydrogel swelling ratio and degradation rate. Cell viability was slightly reduced, although without any significant toxicity (cell viability > 50%). All hydrogels containing antibiotic-laden fibrous microparticles displayed antibiofilm effects, with the dentin substrate showing nearly complete elimination of viable bacteria. Altogether, our findings suggest that the engineered injectable antibiotic-laden fibrous microparticles hydrogels hold clinical prospects for endodontic infection ablation.
Obesity and Male Reproduction: Do Sirtuins Play a Role?
Authors: Barbagallo Federica , La Vignera Sandro , Cannarella Rossella , Mongioì Laura M. , Garofalo Vincenzo , Leanza Claudia , Marino Marta , Calogero Aldo E. , Condorelli Rosita A.
Published: January 2022

Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years.
Soluble CD146 as a Potential Target for Preventing Triple Negative Breast Cancer MDA-MB-231 Cell Growth and Dissemination
Authors: Sharma Akshita , Joshkon Ahmad , Ladjimi Aymen , Traboulsi Waël , Bachelier Richard , Robert Stéphane , Foucault-Bertaud Alexandrine , Leroyer Aurélie S. , Bardin Nathalie , Somasundaram Indumathi , Blot-Chabaud Marcel
Published: January 2022

Background: Triple Negative Breast Cancers (TNBC) are the most aggressive breast cancers and lead to poor prognoses. This is due to a high resistance to therapies, mainly because of the presence of Cancer Stem Cells (CSCs). Plasticity, a feature of CSCs, is acquired through the Epithelial to Mesenchymal Transition (EMT), a process that has been recently shown to be regulated by a key molecule, CD146. Of interest, CD146 is over-expressed in TNBC. Methods: The MDA-MB-231 TNBC cell line was used as a model to study the role of CD146 and its secreted soluble form (sCD146) in the development and dissemination of TNBC using in vitro and in vivo studies. Results: High expression of CD146 in a majority of MDA-MB-231 cells leads to an increased secretion of sCD146 that up-regulates the expression of EMT and CSC markers on the cells. These effects can be blocked with a specific anti-sCD146 antibody, M2J-1 mAb. M2J-1 mAb was able to reduce tumour development and dissemination in a model of cells xenografted in nude mice and an experimental model of metastasis, respectively, in part through its effects on CSC. Conclusion: We propose that M2J-1 mAb could be used as an additional therapeutic approach to fight TNBC.
New Insights and Potential Therapeutic Targeting of CB2 Cannabinoid Receptors in CNS Disorders
Authors: Kibret Berhanu Geresu , Ishiguro Hiroki , Horiuchi Yasue , Onaivi Emmanuel S.
Published: January 2022

The endocannabinoid system (ECS) is ubiquitous in most human tissues, and involved in the regulation of mental health. Consequently, its dysregulation is associated with neuropsychiatric and neurodegenerative disorders. Together, the ECS and the expanded endocannabinoidome (eCBome) are composed of genes coding for CB1 and CB2 cannabinoid receptors (CB1R, CB2R), endocannabinoids (eCBs), and the metabolic enzyme machinery for their synthesis and catabolism. The activation of CB1R is associated with adverse effects on the central nervous system (CNS), which has limited the therapeutic use of drugs that bind this receptor. The discovery of the functional neuronal CB2R raised new possibilities for the potential and safe targeting of the ECS for the treatment of CNS disorders. Previous studies were not able to detect CB2R mRNA transcripts in brain tissue and suggested that CB2Rs were absent in the brain and were considered peripheral receptors. Studies done on the role of CB2Rs as a potential therapeutic target for treating different disorders revealed the important putative role of CB2Rs in certain CNS disorders, which requires further clinical validation. This review addresses recent advances on the role of CB2Rs in neuropsychiatric and neurodegenerative disorders, including, but not limited to, anxiety, depression, schizophrenia, Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD) and addiction.
Lung Microbiome in Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Diseases
Authors: Amati Francesco , Stainer Anna , Mantero Marco , Gramegna Andrea , Simonetta Edoardo , Suigo Giulia , Voza Antonio , Nambiar Anoop M. , Cariboni Umberto , Oldham Justin , Molyneaux Philip L. , Spagnolo Paolo , Blasi Francesco , Aliberti Stefano
Published: January 2022

Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis and progression of interstitial lung diseases. In recent years, the utilization of culture-independent methodologies has allowed the identification of complex and dynamic communities of microbes, in patients with interstitial lung diseases. However, the potential mechanisms by which these changes may drive disease pathogenesis and progression are largely unknown. The aim of this review is to discuss the role of the altered lung microbiome in several interstitial lung diseases. Untangling the host–microbiome interaction in the lung and airway of interstitial lung disease patients is a research priority. Thus, lung dysbiosis is a potentially treatable trait across several interstitial lung diseases, and its proper characterization and treatment might be crucial to change the natural history of these diseases and improve outcomes.
Host- and Age-Dependent Transcriptional Changes in Mycobacterium tuberculosis Cell Envelope Biosynthesis Genes after Exposure to Human Alveolar Lining Fluid
Authors: Allué-Guardia Anna , Garcia-Vilanova Andreu , Olmo-Fontánez Angélica M. , Peters Jay , Maselli Diego J. , Wang Yufeng , Turner Joanne , Schlesinger Larry S. , Torrelles Jordi B.
Published: January 2022

Tuberculosis (TB) infection, caused by the airborne pathogen Mycobacterium tuberculosis (M.tb), resulted in almost 1.4 million deaths in 2019, and the number of deaths is predicted to increase by 20% over the next 5 years due to the COVID-19 pandemic. Upon reaching the alveolar space, M.tb comes into close contact with the lung mucosa before and after its encounter with host alveolar compartment cells. Our previous studies show that homeostatic, innate soluble components of the alveolar lining fluid (ALF) can quickly alter the cell envelope surface of M.tb upon contact, defining subsequent M.tb–host cell interactions and infection outcomes in vitro and in vivo. We also demonstrated that ALF from 60+ year old elders (E-ALF) vs. healthy 18- to 45-year-old adults (A-ALF) is dysfunctional, with loss of homeostatic capacity and impaired innate soluble responses linked to high local oxidative stress. In this study, a targeted transcriptional assay shows that M.tb exposure to human ALF alters the expression of its cell envelope genes. Specifically, our results indicate that A-ALF-exposed M.tb upregulates cell envelope genes associated with lipid, carbohydrate, and amino acid metabolism, as well as genes associated with redox homeostasis and transcriptional regulators. Conversely, M.tb exposure to E-ALF shows a lesser transcriptional response, with most of the M.tb genes unchanged or downregulated. Overall, this study indicates that M.tb responds and adapts to the lung alveolar environment upon contact, and that the host ALF status, determined by factors such as age, might play an important role in determining infection outcome.
Involvement of the Innate Immune System in the Pathogenesis of Chronic Obstructive Pulmonary Disease
Authors: Kotlyarov Stanislav
Published: January 2022

Chronic obstructive pulmonary disease (COPD) is a common, socially significant disease characterized by progressive airflow limitation due to chronic inflammation in the bronchi. Although the causes of COPD are considered to be known, the pathogenesis of the disease continues to be a relevant topic of study. Mechanisms of the innate immune system are involved in various links in the pathogenesis of COPD, leading to persistence of chronic inflammation in the bronchi, their bacterial colonization and disruption of lung structure and function. Bronchial epithelial cells, neutrophils, macrophages and other cells are involved in the development and progression of the disease, demonstrating multiple compromised immune mechanisms.
Electrospun PEO/rGO Scaffolds: The Influence of the Concentration of rGO on Overall Properties and Cytotoxicity
Authors: Ivanoska-Dacikj Aleksandra , Makreski Petre , Geskovski Nikola , Karbowniczek Joanna , Stachewicz Urszula , Novkovski Nenad , Tanasić Jelena , Ristić Ivan , Bogoeva-Gaceva Gordana
Published: January 2022

Reduced graphene oxide (rGO) is one of the graphene derivatives that can be employed to engineer bioactive and/or electroactive scaffolds. However, the influence of its low and especially high concentrations on scaffolds’ overall properties and cytotoxicity has yet to be explored. In this study, polyethylene oxide (PEO)-based scaffolds containing from 0.1 to 20 wt% rGO were obtained by electrospinning. Morphological, thermal and electrical properties of the scaffolds were characterized by SEM, Raman spectroscopy, XRD, DSC and electrical measurements. The diameter of the fibers decreased from 0.52 to 0.19 µm as the concentration of rGO increased from 0.1 wt% to 20 wt%. The presence of rGO above the percolation threshold (5.7 wt%) resulted in a significantly reduced electrical resistivity of the scaffolds. XRD and Raman analysis revealed delamination of the graphene layers (interlayer spacing increased from 0.36 nm to 0.40–0.41 nm), and exfoliation of rGO was detected for the samples with an rGO concentration lower than 1 wt%. In addition, an evident trend of increasing cell viability as a function of the rGO concentration was evidenced. The obtained results can serve as further guidance for the judicious selection of the rGO content incorporated into the PEO matrix for constructing electroactive scaffolds.
Individual and Binary Mixture Toxicity of Five Nanoparticles in Marine Microalga Heterosigma akashiwo
Authors: Pikula Konstantin , Johari Seyed Ali , Santos-Oliveira Ralph , Golokhvast Kirill
Published: January 2022

The investigation of the combined toxic action of different types of nanoparticles (NPs) and their interaction between each other and with aquatic organisms is an important problem of modern ecotoxicology. In this study, we assessed the individual and mixture toxicities of cadmium and zinc sulfides (CdS and ZnS), titanium dioxide (TiO2), and two types of mesoporous silicon dioxide (with no inclusions (SMB3) and with metal inclusions (SMB24)) by a microalga growth inhibition bioassay. The counting and size measurement of microalga cells and NPs were performed by flow cytometry. The biochemical endpoints were measured by a UV-VIS microplate spectrophotometer. The highest toxicity was observed for SMB24 (EC50, 3.6 mg/L) and CdS (EC50, 21.3 mg/L). A combined toxicity bioassay demonstrated that TiO2 and the SMB3 NPs had a synergistic toxic effect in combinations with all the tested samples except SMB24, probably caused by a “Trojan horse effect”. Sample SMB24 had antagonistic toxic action with CdS and ZnS, which was probably caused by metal ion scavenging.
CRLF1 and CLCF1 in Development, Health and Disease
Authors: Crisponi Laura , Buers Insa , Rutsch Frank
Published: January 2022

Cytokines and their receptors have a vital function in regulating various processes such as immune function, inflammation, haematopoiesis, cell growth and differentiation. The interaction between a cytokine and its specific receptor triggers intracellular signalling cascades that lead to altered gene expression in the target cell and consequent changes in its proliferation, differentiation, or activation. In this review, we highlight the role of the soluble type I cytokine receptor CRLF1 (cytokine receptor-like factor-1) and the Interleukin (IL)-6 cytokine CLCF1 (cardiotrophin-like cytokine factor 1) during development in physiological and pathological conditions with particular emphasis on Crisponi/cold-induced sweating syndrome (CS/CISS) and discuss new insights, challenges and possibilities arising from recent studies.
Development of the Ontogenetic Self-Regulation Clock
Authors: Goldstein Ferber Sari , Weller Aron , Ben-Shachar Michal , Klinger Gil , Geva Ronny
Published: January 2022

To date, there is no overarching proposition for the ontogenetic-neurobiological basis of self-regulation. This paper suggests that the balanced self-regulatory reaction of the fetus, newborn and infant is based on a complex mechanism starting from early brainstem development and continuing to progressive control of the cortex over the brainstem. It is suggested that this balance occurs through the synchronous reactivity between the sympathetic and parasympathetic systems, both which originate from the brainstem. The paper presents an evidence-based approach in which molecular excitation-inhibition balance, interchanges between excitatory and inhibitory roles of neurotransmitters as well as cardiovascular and white matter development across gestational ages, are shown to create sympathetic-parasympathetic synchrony, including the postnatal development of electroencephalogram waves and vagal tone. These occur in developmental milestones detectable in the same time windows (sensitive periods of development) within a convergent systematic progress. This ontogenetic stepwise process is termed “the self-regulation clock” and suggest that this clock is located in the largest connection between the brainstem and the cortex, the corticospinal tract. This novel evidence-based new theory paves the way towards more accurate hypotheses and complex studies of self-regulation and its biological basis, as well as pointing to time windows for interventions in preterm infants. The paper also describes the developing indirect signaling between the suprachiasmatic nucleus and the corticospinal tract. Finally, the paper proposes novel hypotheses for molecular, structural and functional investigation of the “clock” circuitry, including its associations with other biological clocks. This complex circuitry is suggested to be responsible for the developing self-regulatory functions and their neurobehavioral correlates.
Deranged Myocardial Fatty Acid Metabolism in Heart Failure
Authors: Yamamoto Tsunehisa , Sano Motoaki
Published: January 2022

The heart requires fatty acids to maintain its activity. Various mechanisms regulate myocardial fatty acid metabolism, such as energy production using fatty acids as fuel, for which it is known that coordinated control of fatty acid uptake, β-oxidation, and mitochondrial oxidative phosphorylation steps are important for efficient adenosine triphosphate (ATP) production without unwanted side effects. The fatty acids taken up by cardiomyocytes are not only used as substrates for energy production but also for the synthesis of triglycerides and the replacement reaction of fatty acid chains in cell membrane phospholipids. Alterations in fatty acid metabolism affect the structure and function of the heart. Recently, breakthrough studies have focused on the key transcription factors that regulate fatty acid metabolism in cardiomyocytes and the signaling systems that modify their functions. In this article, we reviewed the latest research on the role of fatty acid metabolism in the pathogenesis of heart failure and provide an outlook on future challenges.
Hemopexin and Cancer
Authors: Fiorito Veronica , Tolosano Emanuela
Published: January 2022

Hemopexin is the plasma protein with the highest affinity for heme. Seminal studies have highlighted its role in different kinds of heme-associated disorders, but its implication in cancer has been neglected for a long time. Considering the emerging importance of heme in tumors, the present review proposes an update of the works investigating hemopexin involvement in cancer, with the attempt to stimulate further future studies on this topic.
Anti-Inflammatory Effect of IKK-Activated GSK-3β Inhibitory Peptide Prevented Nigrostriatal Neurodegeneration in the Rodent Model of Parkinson’s Disease
Authors: Lee Seulah , Hong Dong Geun , Yang Seonguk , Kim Jaehoon , Baek Minwoo , Kim Seoyeong , Thirumalai Dinakaran , Chung Hae Young , Chang Seung-Cheol , Lee Jaewon
Published: January 2022

Parkinson’s disease (PD) is a progressive movement disorder caused by nigrostriatal neurodegeneration. Since chronically activated neuroinflammation accelerates neurodegeneration in PD, we considered that modulating chronic neuroinflammatory response might provide a novel therapeutic approach. Glycogen synthase kinase 3 (GSK-3) is a multifunctional serine/threonine protein kinase with two isoforms, GSK-3α and GSK-3β, and GSK-3β plays crucial roles in inflammatory response, which include microglial migration and peripheral immune cell activation. GSK-3β inhibitory peptide (IAGIP) is specifically activated by activated inhibitory kappa B kinase (IKK), and its therapeutic effects have been demonstrated in a mouse model of colitis. Here, we investigated whether the anti-inflammatory effects of IAGIP prevent neurodegeneration in the rodent model of PD. IAGIP significantly reduced MPP+-induced astrocyte activation and inflammatory response in primary astrocytes without affecting the phosphorylations of ERK or JNK. In addition, IAGIP inhibited LPS-induced cell migration and p65 activation in BV-2 microglial cells. In vivo study using an MPTP-induced mouse model of PD revealed that intravenous IAGIP effectively prevented motor dysfunction and nigrostriatal neurodegeneration. Our findings suggest that IAGIP has a curative potential in PD models and could offer new therapeutic possibilities for targeting PD.
Newborn Screening for X-Linked Adrenoleukodystrophy: The Initial Illinois Experience
Authors: Burton Barbara K. , Hickey Rachel , Hitchins Lauren , Shively Vera , Ehrhardt Joan , Ashbaugh Laura , Peng Yin , Basheeruddin Khaja
Published: January 2022

X-linked adrenoleukodystrophy (X-ALD) is a genetic neurodegenerative disorder with an approximate incidence of 1 in 14,700 births. Both males and females are affected. Approximately one-third of affected males develop childhood cerebral adrenoleukodystrophy, which progresses rapidly to severe disability and death. In these cases, early surveillance and treatment can be lifesaving, but only if initiated before the onset of neurologic symptoms. Therefore, X-ALD was added to the Recommended Uniform Screening Panel. We report outcomes of the initial screening of approximately 276,000 newborns in Illinois. The lipid C26:0 lysophosphatidylcholine (C26:0-LPC) was measured in dried blood spots (DBS) using liquid chromatography with tandem mass spectrometry. Results ≥ 0.28 µmol/L were considered screen positive. Of 18 screen positive results detected, 12 cases were confirmed. Results were reported as borderline if initial and repeat analyses were ≥0.18 and <0.28 µmol/L. Of the 73 borderline screen results, 57 were normal after analysis of a second sample. Five X-ALD cases were identified from borderline screens. Newborn screening of X-ALD was successfully implemented in Illinois, and results were comparable to reports from other states. Early identification of infants with this potentially life-threatening disorder will significantly improve outcomes for these children.
Bacterial Survey in the Guts of Domestic Silkworms, Bombyx mori L.
Authors: Dee Tan Ivan Y. , Bautista Ma. Anita M.
Published: January 2022

Silkworm, Bombyx mori L., research involves studies on improving strains for enhanced sustainability of high-quality silk production. Several of these have investigated the factors affecting growth and development of silkworm larvae and cocoon characteristics that subsequently affect the yield and quality of silk. The gut microbiota has been reported to impact growth and development of silkworms and has been linked, in particular, with absorption and utilization of nutrients and immunity to diseases. The silkworm strains maintained in the Philippines lack sufficient biological data for use in strain improvement. This prompted efforts to augment the data by profiling bacterial communities through high-throughput 16S rRNA gene amplicon sequencing and analysis in four of the local silkworm strains that are bred and maintained in the country. Results of the study showed that the four silkworm strains are abundant in bacteria that belong to the genera Pseudomonas, Sphingomonas, Delftia, Methylobacterium and Acinetobacter. Results also showed that bacterial diversity and evenness increase as larvae mature, which can be correlated to larval development and shifts in the amount and age of mulberry leaves the larvae consume.
Improvement of the Liquefied Natural Gas Vapor Utilization System Using a Gas Ejector
Authors: Bolobov Victor , Martynenko Yana Vladimirovna , Voronov Vladimir , Latipov Ilnur , Popov Grigory
Published: January 2022

The production, transportation, and storage of liquefied natural gas (LNG) is a promising area in the gas industry due to a number of the fuel’s advantages, such as its high energy intensity indicators, its reduced storage volume compared to natural gas in the gas-air state, and it ecological efficiency. However, LNG storage systems feature a number of disadvantages, among which is the boil-off gas (BOG) recovery from an LNG tank by flaring it or discharging it to the atmosphere. Previous attempts to boil-off gas recovery using compressors, in turn, feature such disadvantages as large capital investments and operating costs, as well as low reliability rates. The authors of this article suggest a technical solution to this problem that consists in using a gas ejector for boil-off gas recovery. Natural gas from a high-pressure gas pipeline is proposed as a working fluid entraining the boil-off gas. The implementation of this method was carried out according to the developed algorithm. The proposed technical solution reduced capital costs (by approximately 170 times), metal consumption (by approximately 100 times), and power consumption (by approximately 55 kW), and improved the reliability of the system compared to a compressor unit. The sample calculation of a gas ejector for the boil-off gas recovery from an LNG tank with a capacity of 300 m3 shows that the ejector makes it possible to increase the boil-off gas pressure in the system by up to 1.13 MPa, which makes it possible to not use the first-stage compressor unit for the compression of excess vapours.
Individual Contributions of Cardiac Ion Channels on Atrial Repolarization and Reentrant Waves: A Multiscale In-Silico Study
Authors: Sutanto Henry
Published: January 2022

The excitation, contraction, and relaxation of an atrial cardiomyocyte are maintained by the activation and inactivation of numerous cardiac ion channels. Their collaborative efforts cause time-dependent changes of membrane potential, generating an action potential (AP), which is a surrogate marker of atrial arrhythmias. Recently, computational models of atrial electrophysiology emerged as a modality to investigate arrhythmia mechanisms and to predict the outcome of antiarrhythmic therapies. However, the individual contribution of atrial ion channels on atrial action potential and reentrant arrhythmia is not yet fully understood. Thus, in this multiscale in-silico study, perturbations of individual atrial ionic currents (INa, Ito, ICaL, IKur, IKr, IKs, IK1, INCX and INaK) in two in-silico models of human atrial cardiomyocyte (i.e., Courtemanche-1998 and Grandi-2011) were performed at both cellular and tissue levels. The results show that the inhibition of ICaL and INCX resulted in AP shortening, while the inhibition of IKur, IKr, IKs, IK1 and INaK prolonged AP duration (APD). Particularly, in-silico perturbations (inhibition and upregulation) of IKr and IKs only minorly affected atrial repolarization in the Grandi model. In contrast, in the Courtemanche model, the inhibition of IKr and IKs significantly prolonged APD and vice versa. Additionally, a 50% reduction of Ito density abbreviated APD in the Courtemanche model, while the same perturbation prolonged APD in the Grandi model. Similarly, a strong model dependence was also observed at tissue scale, with an observable IK1-mediated reentry stabilizing effect in the Courtemanche model but not in the Grandi atrial model. Moreover, the Grandi model was highly sensitive to a change on intracellular Ca2+ concentration, promoting a repolarization failure in ICaL upregulation above 150% and facilitating reentrant spiral waves stabilization by ICaL inhibition. Finally, by incorporating the previously published atrial fibrillation (AF)-associated ionic remodeling in the Courtemanche atrial model, in-silico modeling revealed the antiarrhythmic effect of IKr inhibition in both acute and chronic settings. Overall, our multiscale computational study highlights the strong model-dependent effects of ionic perturbations which could affect the model’s accuracy, interpretability, and prediction. This observation also suggests the need for a careful selection of in-silico models of atrial electrophysiology to achieve specific research aims.
Microcatheter–Assisted Circumferential Trabeculotomy in Primary Congenital Glaucoma: Long-Term Clinical Outcomes
Authors: Fontana Luigi , Neri Alberto
Published: January 2022

Purpose: The purpose of this study was to report the long-term efficacy and clinical outcomes of microcatheter-assisted circumferential trabeculotomy (MCT) in children with primary congenital glaucoma (PCG). Methods: This is a single-center retrospective study including consecutive children with PCG who underwent MCT with > two years follow up. The primary outcome was surgical success, defined as intraocular pressure (IOP) ≤ 21 mmHg with (qualified) or without (complete) medications, measured at six months, one year, and then annually. Secondary outcomes were visual acuity (VA), refraction, axial length (AXL), complications, reinterventions, and number of medications. Results: Twelve eyes of ten patients were included. In eight children only one eye was affected. The mean ± standard deviation (SD) age at surgery was 6.3 ± 4.1 months. The mean postoperative follow-up was 66 ± 35 months. The mean IOP was 34.3 ± 9.6 mmHg preoperatively and 14.6 ± 2.3 mmHg postoperatively at the last visit (p < 0.001). Complete success was achieved at all time points in 10 out of 12 eyes, while 2 eyes had a qualified success. At three years of age, the mean VA of the operated eyes was 0.25 ± 0.12 logMAR, the mean spherical equivalent was −0.78 ± 1.43 diopters, and the mean AXL was 23.78 mm. Transient hyphema was the only complication observed. None of the children required additional glaucoma surgery. Conclusions: Circumferential trabeculotomy for PCG effectively lowers the IOP at more than two years after surgery. Following this procedure, the prognosis for the visual function is good, and the refractive error is low. Postoperative complications were not significant.
Cardiac Rehabilitation in Patients with Peripheral Artery Disease—A Literature Review in COVID-19 Era
Authors: Anghel Razvan , Adam Cristina Andreea , Marcu Dragos Traian Marius , Mitu Ovidiu , Mitu Florin
Published: January 2022

Cardiac rehabilitation (CR) is an integral part of the management of various cardiovascular disease such as coronary artery disease (CAD), peripheral artery disease (PAD), or chronic heart failure (CHF), with proven morbidity and mortality benefits. This article aims to review and summarize the scientific literature related to cardiac rehabilitation programs for patients with PAD and how they were adapted during the COVID-19 pandemic. The implementation of CR programs has been problematic since the COVID-19 pandemic due to social distancing and work-related restrictions. One of the main challenges for physicians and health systems alike has been the management of PAD patients. COVID-19 predisposes to coagulation disorders that can lead to severe thrombotic events. Home-based walking exercises are more accessible and easier to accept than supervised exercise programs. Cycling or other forms of exercise are more entertaining or challenging alternatives to exercise therapy. Besides treadmill exercises, upper- and lower-extremity ergometry also has great functional benefits, especially regarding walking endurance. Supervised exercise therapy has a positive impact on both functional capacity and also on the quality of life of such patients. The most effective manner to acquire this seems to be by combining revascularization therapy and supervised exercise. Rehabilitation programs proved to be a mandatory part of the integrative approach in these cases, increasing quality of life, and decreasing stress levels, depression, and anxiety.
Multidisciplinary Care of Patients with Facial Palsy: Treatment of 1220 Patients in a German Facial Nerve Center
Authors: Steinhäuser Jonathan , Volk Gerd Fabian , Thielker Jovanna , Geitner Maren , Kuttenreich Anna-Maria , Klingner Carsten M. , Dobel Christian , Guntinas-Lichius Orlando
Published: January 2022

To determine treatment and outcome in a tertiary multidisciplinary facial nerve center, a retrospective observational study was performed of all patients referred between 2007 and 2018. Facial grading with the Stennert index, the Facial Clinimetric Evaluation (FaCE) scale, and the Facial Disability Index (FDI) were used for outcome evaluation; 1220 patients (58.4% female, median age: 50 years; chronic palsy: 42.8%) were included. Patients with acute and chronic facial palsy were treated in the center for a median of 3.6 months and 10.8 months, respectively. Dominant treatment in the acute phase was glucocorticoids ± acyclovir (47.2%), followed by a significant improvement of all outcome measures (p < 0.001). Facial EMG biofeedback training (21.3%) and botulinum toxin injections (11%) dominated the treatment in the chronic phase, all leading to highly significant improvements according to facial grading, FDI, and FaCE (p < 0.001). Upper eyelid weight (3.8%) and hypoglossal–facial-nerve jump suture (2.5%) were the leading surgical methods, followed by improvement of facial motor function (p < 0.001) and facial-specific quality of life (FDI, FaCE; p < 0.05). A standardized multidisciplinary team approach in a facial nerve center leads to improved facial and emotional function in patients with acute or chronic facial palsy.
Gingival Displacement in the Vertical and Horizontal Dimension under the Condition of Mild Gingivitis—A Randomized Clinical Study
Authors: Kuhn Katharina , Zügel David , Korbay Victor-Sebastian A. , Papas Thomas , Schnutenhaus Sigmar , Luthardt Ralph G. , Dreyhaupt Jens , Rudolph Heike
Published: January 2022

This randomized clinical study aimed at quantifying the gingival displacement performance in the vertical and horizontal directions of the 3M™ Astringent Retraction Paste (3M Oral Care, Seefeld, Germany) in comparison with the double-cord technique with aluminum chloride as an astringent. Afterward, any soft-tissue changes were assessed for 12 months. After inducing mild gingivitis, 18 probands received the intervention ‘cord’ and 22 probands received the intervention ‘paste’ at the palatal half of upper premolars prior to conventional impression making. The resulting plaster casts were digitized and analyzed for the vertical and horizontal gingival displacement, applying a newly developed computer-assisted methodology. The entire palatal half of the tooth was evaluated instead of only single sites. Under the condition of mild gingivitis, the gingival displacement performance was comparable for both techniques in the horizontal direction (width) and only somewhat better for the cord technique in the vertical direction (depth). The magnitude of displacement was in a similar range in both directions, with somewhat higher values in the vertical direction. The marginal gingiva height changes were of such low extent during the follow-up period of 12 months with only minimally higher values for the paste that they cannot be considered as clinically relevant recessions.
Mental Health Well-Being and Attitudes on Mental Health Disorders among Family Physicians during COVID-19 Pandemic: A Connection with Resilience and Healthy Lifestyle
Authors: Vilovic Tina , Bozic Josko , Zuzic Furlan Sanja , Vilovic Marino , Kumric Marko , Martinovic Dinko , Rusic Doris , Rada Marko , Tomicic Marion
Published: January 2022

Family physicians (FPs) are exposed to high amounts of stress, and could be susceptible to the development of mental health disorders (MHD), especially after the emergence of the COVID-19 pandemic. The aim of the current study was to assess MHD history, attitudes toward MHDs and stress-coping strategies in FPs. An additional goal was to estimate their comprehensive well-being and investigate connections with resilience and a healthy lifestyle. A total of 483 FPs submitted their responses via online survey. MHD attitudes were assessed with the according questionnaires, while burnout levels, healthy lifestyle, resilience, job and life satisfaction were estimated with validated scales. Results have shown that 32.5% of FPs disclosed positive MHD history, while 68.7% used professional help. Resilience and healthy lifestyle levels were significantly higher in MHD negative FPs (p < 0.001), while burnout levels were lower (p < 0.001). Moreover, healthy lifestyle (β = 0.03, p < 0.001) was an independent correlate of resilience, while healthy lifestyle (β = −0.35, p < 0.001, and resilience (β = −1.82, p < 0.001) were of burnout levels. Finally, resilience (OR = 0.387, p < 0.001) and healthy lifestyle (OR = 0.970, p = 0.021) were shown as independent predictors of positive MHD history status. Strong promotion and education of FP population regarding resilience and healthy lifestyle should be utilized in practice in order to alleviate the possibility of mental health disturbances and the according consequences.
Early Spirometry Following Bronchoscopic Lung Volume Reduction with Endobronchial Valves
Authors: Bezel Pascal , Wani Jasmin , Wiederkehr Gilles , Bodmer Christa , Steinack Carolin , Franzen Daniel P.
Published: January 2022

Bronchoscopic lung volume reduction (BLVR) by endobronchial valve (EBV) implantation has been shown to improve dyspnea, pulmonary function, exercise capacity, and quality of life in highly selected patients with severe emphysema and hyperinflation. The most frequent adverse event is a pneumothorax (PTX), occurring in approximately one-fifth of the cases due to intrathoracic volume shifts. The majority of these incidents are observed within 48 h post-procedure. However, the delayed occurrence of PTX after hospital discharge is a matter of concern. There is currently no approved concept for its prevention. Particularly, it is unknown whether and when respiratory manoeuvers such as spirometry post EBV treatment are feasible and safe. As per standard operating procedure at the University Hospital Zurich, early spirometry is scheduled after BLVR and prior to the discharge of the patient in order to monitor treatment success. The aim of our retrospective study was to investigate the feasibility and safety of early spirometry. In addition, we hypothesized that early spirometry could be useful to identify patients at risk for late PTX, which may occur after hospital discharge. All patients who underwent BLVR using EBVs between January 2018 and January 2020 at our hospital were enrolled in this study. After excluding 16 patients diagnosed post-procedure with PTX and four patients for other reasons, early spirometry was performed in 61 cases. There was neither a clinically relevant PTX during or after early spirometry nor a late PTX following hospital discharge. In conclusion, we found early spirometry, conducted not sooner than three days following EBV treatment, to be feasible and safe. Furthermore, early spirometry seems to be a useful predictor for successful BLVR, and it may help to decide whether a patient can be discharged. Given the small sample size and the retrospective design of our study, a prospective study that includes routine chest imaging after early spirometry to definitively exclude PTX is needed to recommend early spirometry as part of the standard protocol following EBV treatment.
Involvement of Peripheral Monocytes with IL-1β in the Pathogenesis of West Syndrome
Authors: Takamatsu Tomoko , Yamanaka Gaku , Ohno Koko , Hayashi Kanako , Watanabe Yusuke , Takeshita Mika , Suzuki Shinji , Morichi Shinichiro , Go Soken , Ishida Yu , Oana Shingo , Kashiwagi Yasuyo , Kawashima Hisashi
Published: January 2022

Neuroinflammation has been implicated in the pathogenesis of West syndrome (WS). Inflammatory cytokines, including interleukin-1β(IL-1β), have been reported to be associated with epilepsy. However, the assessment of cytokine changes in humans is not always simple or deterministic. This study aimed to elucidate the immunological mechanism of WS. We examined the intracellular cytokine profiles of peripheral blood cells collected from 13 patients with WS, using flow cytometry, and measured their serum cytokine levels. These were compared with those of 10 age-matched controls. We found that the WS group had significantly higher percentages of inter IL-1β, interleukin-1 receptor antagonist (IL-1RA)-positive monocytes, and interferon gamma (IFN-γ) in their CD8+ T cells than the control group. Interestingly, the group with sequelae revealed significantly lower levels of intracellular IFN-γ and IL-6 in their CD8+ T and CD4+ T cells, respectively, than the group without sequelae. There was no correlation between the ratios of positive cells and the serum levels of a particular cytokine in the WS patients. These cytokines in the peripheral immune cells might be involved in the neuroinflammation of WS, even in the absence of infectious or immune disease. Overall, an immunological approach using flow cytometry analysis might be useful for immunological studies of epilepsy.
Multi-Level Processes and Retina–Brain Pathways of Photic Regulation of Mood
Authors: Maruani Julia , Geoffroy Pierre A.
Published: January 2022

Light exerts powerful biological effects on mood regulation. Whereas the source of photic information affecting mood is well established at least via intrinsically photosensitive retinal ganglion cells (ipRGCs) secreting the melanopsin photopigment, the precise circuits that mediate the impact of light on depressive behaviors are not well understood. This review proposes two distinct retina–brain pathways of light effects on mood: (i) a suprachiasmatic nucleus (SCN)-dependent pathway with light effect on mood via the synchronization of biological rhythms, and (ii) a SCN-independent pathway with light effects on mood through modulation of the homeostatic process of sleep, alertness and emotion regulation: (1) light directly inhibits brain areas promoting sleep such as the ventrolateral preoptic nucleus (VLPO), and activates numerous brain areas involved in alertness such as, monoaminergic areas, thalamic regions and hypothalamic regions including orexin areas; (2) moreover, light seems to modulate mood through orexin-, serotonin- and dopamine-dependent pathways; (3) in addition, light activates brain emotional processing areas including the amygdala, the nucleus accumbens, the perihabenular nucleus, the left hippocampus and pathways such as the retina–ventral lateral geniculate nucleus and intergeniculate leaflet–lateral habenula pathway. This work synthetizes new insights into the neural basis required for light influence mood
The Development of Peritoneal Metastasis from Gastric Cancer and Rationale of Treatment According to the Mechanism
Authors: Yonemura Yutaka , Ishibashi Haruaki , Mizumoto Akiyoshi , Tukiyama Gorou , Liu Yang , Wakama Satoshi , Sako Shouzou , Takao Nobuyuki , Kitai Toshiyuki , Katayama Kanji , Kamada Yasuyuki , Taniguchi Keizou , Fujimoto Daisuke , Endou Yoshio , Miura Masahiro
Published: January 2022

In the present article, we describe the normal structure of the peritoneum and review the mechanisms of peritoneal metastasis (PM) from gastric cancer (GC). The structure of the peritoneum was studied by a double-enzyme staining method using alkaline-phosphatase and 5′-nucreotidase, scanning electron microscopy, and immunohistological methods. The fundamental structure consists of three layers, mesothelial cells and a basement membrane (layer 1), macula cribriformis (MC) (layer 2), and submesothelial connective tissue containing blood vessels and initial lymphatic vessels, attached to holes in the MC (layer 3). Macro molecules and macrophages migrate from mesothelial stomata to the initial lymphatic vessels through holes in the MC. These structures are characteristically found in the diaphragm, omentum, paracolic gutter, pelvic peritoneum, and falciform ligament. The first step of PM is spillage of cancer cells (peritoneal free cancer cells; PFCCs) into the peritoneal cavity from the serosal surface of the primary tumor or cancer cell contamination from lymphatic and blood vessels torn during surgical procedures. After PFCCs adhere to the peritoneal surface, PMs form by three processes, i.e., (1) trans-mesothelial metastasis, (2) trans-lymphatic metastasis, and (3) superficial growing metastasis. Because the intraperitoneal (IP) dose intensity is significantly higher when generated by IP chemotherapy than by systemic chemotherapy, IP chemotherapy has a great role in the treatment of PFCCs, superficial growing metastasis, trans-lymphatic metastasis and in the early stages of trans-mesothelial metastasis. However, an established trans-mesothelial metastasis has its own interstitial tissue and vasculature which generate high interstitial pressure. Accordingly, it is reasonable to treat established trans-mesothelial metastasis by bidirectional chemotherapy from both IP and systemic chemotherapy.