bluuebunny/crossref_metadata_2025 huggingface dataset:
Pial Vessel-Associated Microglia/Macrophages Increase in Female Dahl-SS/Jr Rats Independent of Pregnancy History
Authors: Warrington Junie P. , Shao Qingmei , Clayton Ahsia M. , Maeda Kenji J. , Beckett Ashtin G. , Garrett Michael R. , Sasser Jennifer M.
Published: March 2022

As the resident immune cells of the central nervous system, microglia have a wide range of functions such as surveillance, phagocytosis, and signaling through production of chemokines and cytokines. Recent studies have identified and characterized macrophages residing at the meninges, a series of layers surrounding the brain and spinal cord. While perivascular microglia within the brain parenchyma increase following chronic hypertension, there are no reports of changes at the meninges, and specifically, associated with the pial vasculature. Thus, we used female Sprague Dawley and Dahl salt-sensitive (SS/Jr) rat brains, stained for ionized calcium-binding adapter molecule (Iba1), and characterized microglia/macrophages associated with pial vessels in the posterior brain. Results indicate that Iba1+ pial vessel-associated microglia (PVAM) completely surrounded the vessels in brains from the Dahl-SS/Jr rats. PVAM density was significantly higher and distance between PVAMs lower in Dahl-SS/Jr compared to the Sprague Dawley rat brains. Pregnancy history did not affect these findings. While the functional role of these cells are not known, we contextualize our novel findings with that of other studies assessing or characterizing myeloid cells at the borders of the CNS (meninges and choroid plexus) and perivascular macrophages and propose their possible origin in the Dahl-SS/Jr model of chronic hypertension.
Pathophysiology of Chronic Liver Disease Development
Authors: Fromme Malin , Strnad Pavel
Published: March 2022

Chronic liver disease is a major public threat and the second leading cause of loss of working life years in Europe [...]
Effect of Copper on Expression of Functional Genes and Proteins Associated with Bradyrhizobium diazoefficiens Denitrification
Authors: Pacheco Pedro J. , Cabrera Juan J. , Jiménez-Leiva Andrea , Bedmar Eulogio J. , Mesa Socorro , Tortosa Germán , Delgado María J.
Published: March 2022

Nitrous oxide (N2O) is a powerful greenhouse gas that contributes to climate change. Denitrification is one of the largest sources of N2O in soils. The soybean endosymbiont Bradyrhizobium diazoefficiens is a model for rhizobial denitrification studies since, in addition to fixing N2, it has the ability to grow anaerobically under free-living conditions by reducing nitrate from the medium through the complete denitrification pathway. This bacterium contains a periplasmic nitrate reductase (Nap), a copper (Cu)-containing nitrite reductase (NirK), a c-type nitric oxide reductase (cNor), and a Cu-dependent nitrous oxide reductase (Nos) encoded by the napEDABC, nirK, norCBQD and nosRZDFYLX genes, respectively. In this work, an integrated study of the role of Cu in B. diazoefficiens denitrification has been performed. A notable reduction in nirK, nor, and nos gene expression observed under Cu limitation was correlated with a significant decrease in NirK, NorC and NosZ protein levels and activities. Meanwhile, nap expression was not affected by Cu, but a remarkable depletion in Nap activity was found, presumably due to an inhibitory effect of nitrite accumulated under Cu-limiting conditions. Interestingly, a post-transcriptional regulation by increasing Nap and NirK activities, as well as NorC and NosZ protein levels, was observed in response to high Cu. Our results demonstrate, for the first time, the role of Cu in transcriptional and post-transcriptional control of B. diazoefficiens denitrification. Thus, this study will contribute by proposing useful strategies for reducing N2O emissions from agricultural soils.
Swelling, Protein Adsorption, and Biocompatibility In Vitro of Gel Beads Prepared from Pectin of Hogweed Heracleum sosnówskyi Manden in Comparison with Gel Beads from Apple Pectin
Authors: Popov Sergey , Paderin Nikita , Khramova Daria , Kvashninova Elizaveta , Patova Olga , Vityazev Fedor
Published: March 2022

The study aims to develop gel beads with improved functional properties and biocompatibility from hogweed (HS) pectin. HS4 and AP4 gel beads were prepared from the HS pectin and apple pectin (AP) using gelling with calcium ions. HS4 and AP4 gel beads swelled in PBS in dependence on pH. The swelling degree of HS4 and AP4 gel beads was 191 and 136%, respectively, in PBS at pH 7.4. The hardness of HS4 and AP4 gel beads reduced 8.2 and 60 times, respectively, compared with the initial value after 24 h incubation. Both pectin gel beads swelled less in Hanks’ solution than in PBS and swelled less in Hanks’ solution containing peritoneal macrophages than in cell-free Hanks’ solution. Serum protein adsorption by HS4 and AP4 gel beads was 118 ± 44 and 196 ± 68 μg/cm2 after 24 h of incubation. Both pectin gel beads demonstrated low rates of hemolysis and complement activation. However, HS4 gel beads inhibited the LPS-stimulated secretion of TNF-α and the expression of TLR4 and NF-κB by macrophages, whereas AP4 gel beads stimulated the inflammatory response of macrophages. HS4 gel beads adsorbed 1.3 times more LPS and adhered to 1.6 times more macrophages than AP4 gel beads. Thus, HS pectin gel has advantages over AP gel concerning swelling behavior, protein adsorption, and biocompatibility.
Extracellular Vesicles: Interplay with the Extracellular Matrix and Modulated Cell Responses
Authors: Al Halawani Aleen , Mithieux Suzanne M. , Yeo Giselle C. , Hosseini-Beheshti Elham , Weiss Anthony S.
Published: March 2022

The discovery that cells secrete extracellular vesicles (EVs), which carry a variety of regulatory proteins, nucleic acids, and lipids, has shed light on the sophisticated manner by which cells can communicate and accordingly function. The bioactivity of EVs is not only defined by their internal content, but also through their surface associated molecules, and the linked downstream signaling effects they elicit in target cells. The extracellular matrix (ECM) contains signaling and structural molecules that are central to tissue maintenance and repair. Recently, a subset of EVs residing within the extracellular matrix has been identified. Although some roles have been proposed for matrix-bound vesicles, their role as signaling molecules within the ECM is yet to be explored. Given the close association of EVs and the ECM, it is not surprising that EVs partly mediate repair and regeneration by modulating matrix deposition and degradation through their cellular targets. This review addresses unique EV features that allow them to interact with and navigate through the ECM, describes how their release and content is influenced by the ECM, and emphasizes the emerging role of stem-cell derived EVs in tissue repair and regeneration through their matrix-modulating properties.
Comparative Analysis of Bacterial Cellulose Membranes Synthesized by Chosen Komagataeibacter Strains and Their Application Potential
Authors: Kaczmarek Monika , Jędrzejczak-Krzepkowska Marzena , Ludwicka Karolina
Published: March 2022

This article presents a comparative analysis of bacterial cellulose membranes synthesized by several strains of the Komagataeibacter genus in terms of their specific physical, physico-chemical, and mechanical properties. Herein, the aim was to choose the most suitable microorganisms producing cellulosic materials with the greatest potential for the fabrication of bio-inspired nanocomposites. The selection was based on three main steps, starting from the evaluation of BNC biosynthetic efficiency with and without the addition of ethanol, followed by the assessment of mechanical breaking strength, and the physical parameters (compactness, structural integrity, appearance, and thickness) of the obtained biological materials. Ultimately, based on the performed screening procedure, three efficiently growing strains (K. hansenii H3 (6Et), K. rhaeticus K4 (8Et), and Komagataeibacter sp. isolated from balsamic vinegar (12Et)) were chosen for further modifications, enabling additional cellulose functionalization. Here, supplementation of the growth medium with five representative polymeric compounds (citrus/apple pectin, wheat starch, polyvinyl alcohol, polyethylene glycol) led to significant changes in BNC properties, especially dye loading abilities, mechanical strength, and water adsorption/retention capacities. The resulting nanocomposites can be potentially useful in various fields of medicine and industry, and in the future, they may become a practical and cost-effective competitor against commercial biomaterials currently available on the market.
Proteomic Analysis Reveals Enzymes for β-D-Glucan Formation and Degradation in Levilactobacillus brevis TMW 1.2112
Authors: Bockwoldt Julia A. , Meng Chen , Ludwig Christina , Kupetz Michael , Ehrmann Matthias A.
Published: March 2022

Bacterial exopolysaccharide (EPS) formation is crucial for biofilm formation, for protection against environmental factors, or as storage compounds. EPSs produced by lactic acid bacteria (LAB) are appropriate for applications in food fermentation or the pharmaceutical industry, yet the dynamics of formation and degradation thereof are poorly described. This study focuses on carbohydrate active enzymes, including glycosyl transferases (GT) and glycoside hydrolases (GH), and their roles in the formation and potential degradation of O2-substituted (1,3)-β-D-glucan of Levilactobacillus (L.) brevis TMW 1.2112. The fermentation broth of L. brevis TMW 1.2112 was analyzed for changes in viscosity, β-glucan, and D-glucose concentrations during the exponential, stationary, and early death phases. While the viscosity reached its maximum during the stationary phase and subsequently decreased, the β-glucan concentration only increased to a plateau. Results were correlated with secretome and proteome data to identify involved enzymes and pathways. The suggested pathway for β-glucan biosynthesis involved a β-1,3 glucan synthase (GT2) and enzymes from maltose phosphorylase (MP) operons. The decreased viscosity appeared to be associated with cell lysis as the β-glucan concentration did not decrease, most likely due to missing extracellular carbohydrate active enzymes. In addition, an operon was discovered containing known moonlighting genes, all of which were detected in both proteome and secretome samples.
SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In Vitro
Authors: Wu Zhengcun , Zhang Xiuao , Huang Zhangqiong , Ma Kaili
Published: March 2022

Growing cases of patients reported have shown a potential relationship between (severe acute respiratory syndrome coronavirus 2) SARS-CoV-2 infection and Parkinson’s disease (PD). However, it is unclear whether there is a molecular link between these two diseases. Alpha-synuclein (α-Syn), an aggregation-prone protein, is considered a crucial factor in PD pathology. In this study, bioinformatics analysis confirmed favorable binding affinity between α-Syn and SARS-CoV-2 spike (S) protein and nucleocapsid (N) protein, and direct interactions were further verified in HEK293 cells. The expression of α-Syn was upregulated and its aggregation was accelerated by S protein and N protein. It was noticed that SARS-CoV-2 proteins caused Lewy-like pathology in the presence of α-Syn overexpression. By confirming that SARS-CoV-2 proteins directly interact with α-Syn, our study offered new insights into the mechanism underlying the development of PD on the background of COVID-19.
Acid Sphingomyelinase Is a Modulator of Contextual Fear
Authors: Zoicas Iulia , Kornhuber Johannes
Published: March 2022

Acid sphingomyelinase (ASM) regulates a variety of physiological processes and plays an important role in emotional behavior. The role of ASM in fear-related behavior has not been investigated so far. Using transgenic mice overexpressing ASM (ASMtg) and ASM deficient mice, we studied whether ASM regulates fear learning and expression of cued and contextual fear in a classical fear conditioning paradigm, a model used to investigate specific attributes of post-traumatic stress disorder (PTSD). We show that ASM does not affect fear learning as both ASMtg and ASM deficient mice display unaltered fear conditioning when compared to wild-type littermates. However, ASM regulates the expression of contextual fear in a sex-specific manner. While ASM overexpression enhances the expression of contextual fear in both male and female mice, ASM deficiency reduces the expression of contextual fear specifically in male mice. The expression of cued fear, however, is not regulated by ASM as ASMtg and ASM deficient mice display similar tone-elicited freezing levels. This study shows that ASM modulates the expression of contextual fear but not of cued fear in a sex-specific manner and adds a novel piece of information regarding the involvement of ASM in hippocampal-dependent aversive memory.
Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies
Authors: Post Wilke M. , Widomska Joanna , Grens Hilde , Coenen Marieke J. H. , Martens Frank M. J. , Janssen Dick A. W. , IntHout Joanna , Poelmans Geert , Oosterwijk Egbert , Kluivers Kirsten B.
Published: March 2022

Stress urinary incontinence (SUI) is a common and burdensome condition. Because of the large knowledge gap around the molecular processes involved in its pathophysiology, the aim of this review was to provide a systematic overview of genetic variants, gene and protein expression changes related to SUI in human and animal studies. On 5 January 2021, a systematic search was performed in Pubmed, Embase, Web of Science, and the Cochrane library. The screening process and quality assessment were performed in duplicate, using predefined inclusion criteria and different quality assessment tools for human and animal studies respectively. The extracted data were grouped in themes per outcome measure, according to their functions in cellular processes, and synthesized in a narrative review. Finally, 107 studies were included, of which 35 used animal models (rats and mice). Resulting from the most examined processes, the evidence suggests that SUI is associated with altered extracellular matrix metabolism, estrogen receptors, oxidative stress, apoptosis, inflammation, neurodegenerative processes, and muscle cell differentiation and contractility. Due to heterogeneity in the studies (e.g., in examined tissues), the precise contribution of the associated genes and proteins in relation to SUI pathophysiology remained unclear. Future research should focus on possible contributors to these alterations.
Improved Binding Affinity of Omicron’s Spike Protein for the Human Angiotensin-Converting Enzyme 2 Receptor Is the Key behind Its Increased Virulence
Authors: Kumar Rajender , Murugan Natarajan Arul , Srivastava Vaibhav
Published: March 2022

The new variant of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), Omicron, has been quickly spreading in many countries worldwide. Compared to the original virus, Omicron is characterized by several mutations in its genomic region, including the spike protein’s receptor-binding domain (RBD). We have computationally investigated the interaction between the RBD of both the wild type and Omicron variant of SARS-CoV-2 with the human angiotensin-converting enzyme 2 (hACE2) receptor using molecular dynamics and molecular mechanics-generalized Born surface area (MM-GBSA)-based binding free energy calculations. The mode of the interaction between Omicron’s RBD with the hACE2 receptor is similar to the original SARS-CoV-2 RBD except for a few key differences. The binding free energy difference shows that the spike protein of Omicron has an increased affinity for the hACE2 receptor. The mutated residues in the RBD showed strong interactions with a few amino acid residues of hACE2. More specifically, strong electrostatic interactions (salt bridges) and hydrogen bonding were observed between R493 and R498 residues of the Omicron RBD with D30/E35 and D38 residues of the hACE2, respectively. Other mutated amino acids in the Omicron RBD, e.g., S496 and H505, also exhibited hydrogen bonding with the hACE2 receptor. A pi-stacking interaction was also observed between tyrosine residues (RBD-Tyr501: hACE2-Tyr41) in the complex, which contributes majorly to the binding free energies and suggests that this is one of the key interactions stabilizing the formation of the complex. The resulting structural insights into the RBD:hACE2 complex, the binding mode information within it, and residue-wise contributions to the free energy provide insight into the increased transmissibility of Omicron and pave the way to design and optimize novel antiviral agents.
Biocompatible Probes Based on Rare-Earth Doped Strontium Aluminates with Long-Lasting Phosphorescent Properties for In Vitro Optical IMAGING
Authors: Calatayud David G. , Jardiel Teresa , Cordero-Oyonarte Erica , Caballero Amador C. , Villegas Marina , Valle-Noguera Ana , Cruz-Adalia Aranzazu , Peiteado Marco
Published: March 2022

In recent decades, the demand for biomedical imaging tools has grown very rapidly as a key feature for biomedical research and diagnostic applications. Particularly, fluorescence imaging has gained increased attention as a non-invasive, inexpensive technique that allows real-time imaging. However, tissue auto-fluorescence under external illumination, together with a weak tissue penetration of low wavelength excitation light, largely restricts the application of the technique. Accordingly, new types of fluorescent labels are currently being investigated and, in this search, phosphorescent nanoparticles promise great potential, as they combine the interesting size-dependent properties of nanoscale materials with a long-lasting phosphorescence-type emission that allows optical imaging well after excitation (so avoiding autofluorescence). In this work, core-shell structures consisting of SrAlO:Eu,Dy luminescent cores encapsulated within a biocompatible silica shell were prepared, showing a green persistent phosphorescence with an afterglow time of more than 1000 s. A high-energy ball milling procedure was used to reduce the size of the starting phosphors to a size suitable for cellular uptake, while the silica coating was produced by a reverse micelle methodology that eventually allows the excitation and emission light to pass efficiently through the shell. Confocal fluorescence microscopy using HeLa cancer cells confirmed the potential of the all-ceramic composites produced as feasible labels for in vitro optical imaging.
Endometrial Cancer Stem Cells: Where Do We Stand and Where Should We Go?
Authors: Banz-Jansen Constanze , Helweg Laureen P. , Kaltschmidt Barbara
Published: March 2022

Endometrial cancer is one of the most common malignant diseases in women worldwide, with an incidence of 5.9%. Thus, it is the most frequent cancer of the female genital tract, with more than 34,000 women dying, in Europe and North America alone. Endometrial Cancer Stem Cells (CSC) might be drivers of carcinogenesis as well as metastatic and recurrent disease. Therefore, targeting CSCs is of high interest to improve prognosis of patients suffering of advanced or recurrent endometrial cancer. This review describes the current evidence of molecular mechanisms in endometrial CSCs with special emphasis on MYC and NF-κB signaling as well as mitochondrial metabolism. Furthermore, the current status of immunotherapy targeting PD-1 and PD-L1 in endometrial cancer cells and CSCs is elucidated. The outlined findings encourage novel therapies that target signaling pathways in endometrial CSCs as well as immunotherapy as a promising therapeutic approach in the treatment of endometrial cancer to impede cancer progression and prevent recurrence.
Ethical Considerations for Equitable Access to Genomic Sequencing for Critically Ill Neonates in the United States
Authors: P. Fishler Kristen , Euteneuer Joshua C. , Brunelli Luca
Published: March 2022

Rare diseases impact all socio-economic, geographic, and racial groups indiscriminately. Newborn screening (NBS) is an exemplary international public health initiative that identifies infants with rare conditions early in life to reduce morbidity and mortality. NBS theoretically promotes equity through universal access, regardless of financial ability. There is however heterogeneity in access to newborn screening and conditions that are screened throughout the world. In the United States and some other developed countries, NBS is provided to all babies, subsidized by the local or federal government. Although NBS is an equitable test, infants admitted to neonatal intensive care units (NICUs) may not receive similar benefits to healthier infants. Newborns in the NICU may receive delayed and/or multiple newborn screens due to known limitations in interpreting the results with prematurity, total parenteral nutrition, blood transfusions, infection, and life support. Thus, genomic technologies might be needed in addition to NBS for equitable care of this vulnerable population. Whole exome (WES) and genome sequencing (WGS) have been recently studied in critically ill newborns across the world and have shown promising results in shortening diagnostic odysseys and providing clinical utility. However, in certain circumstances several barriers might limit access to these tests. Here, we discuss some of the existing barriers to genomic sequencing in NICUs in the United States, explore the ethical implications related to low access, consider ways to increase access to genomic testing, and offer some suggestions for future research in these areas.
Binuclear Heteroleptic Ru(III) Dithiocarbamate Complexes: A Step towards Tunable Antiproliferative Agents
Authors: Gallio Andrea E. , Brustolin Leonardo , Pettenuzzo Nicolò , Fregona Dolores
Published: March 2022

Binuclear dithiocarbamate complexes of Ru(III) are promising candidates in the search for outstanding metal-based anticancer agents. While different dithiocarbamates have shown ligand-dependent cytotoxicity in homoleptic binuclear Ru(III) complexes, the properties of heteroleptic analogues with different dithiocarbamate (DTC) ligands have yet to be explored. We herein propose the introduction of heteroleptic ligands as tunable features for the development of improved ruthenium-based antiproliferative agents and report a synthetic strategy for their synthesis as well as the evaluation of the cytotoxic activity of a selection of binuclear heteroleptic Ru(III) compounds towards MDA-MB-231 and PC3 cells.
A Comprehensive Study on the Applications of Clays into Advanced Technologies, with a Particular Attention on Biomedicine and Environmental Remediation
Authors: Nisticò Roberto
Published: March 2022

In recent years, a great interest has arisen around the integration of naturally occurring clays into a plethora of advanced technological applications, quite far from the typical fabrication of traditional ceramics. This “second (technological) life” of clays into fields of emerging interest is mainly due to clays’ peculiar properties, in particular their ability to exchange (capture) ions, their layered structure, surface area and reactivity, and their biocompatibility. Since the maximization of clay performances/exploitations passes through the comprehension of the mechanisms involved, this review aims at providing a useful text that analyzes the main goals reached by clays in different fields coupled with the analysis of the structure-property correlations. After providing an introduction mainly focused on the economic analysis of clays global trading, clays are classified basing on their structural/chemical composition. The main relevant physicochemical properties are discussed (particular attention has been dedicated to the influence of interlayer composition on clay properties). Lastly, a deep analysis of the main relevant nonconventional applications of clays is presented. Several case studies describing the use of clays in biomedicine, environmental remediation, membrane technology, additive manufacturing, and sol-gel processes are presented, and results critically discussed.
Integrative Alternative Tactics for Ixodid Control
Authors: Showler Allan T. , Saelao Perot
Published: March 2022

Ixodids (hard ticks), ectoparasitic arthropods that vector the causal agents of many serious diseases of humans, domestic animals, and wildlife, have become increasingly difficult to control because of the development of resistance against commonly applied synthetic chemical-based acaricides. Resistance has prompted searches for alternative, nonconventional control tactics that can be used as part of integrated ixodid management strategies and for mitigating resistance to conventional acaricides. The quest for alternative control tactics has involved research on various techniques, each influenced by many factors, that have achieved different degrees of success. Alternative approaches include cultural practices, ingested and injected medications, biological control, animal- and plant-based substances, growth regulators, and inert desiccant dusts. Research on biological control of ixodids has mainly focused on predators, parasitoid wasps, infective nematodes, and pathogenic bacteria and fungi. Studies on animal-based substances have been relatively limited, but research on botanicals has been extensive, including whole plant, extract, and essential oil effects on ixodid mortality, behavior, and reproduction. The inert dusts kaolin, silica gel, perlite, and diatomaceous earth are lethal to ixodids, and they are impervious to environmental degradation, unlike chemical-based toxins, remaining effective until physically removed.
Exercise Stress Echocardiography in the Diagnostic Evaluation of Heart Failure with Preserved Ejection Fraction
Authors: Harada Tomonari , Kagami Kazuki , Kato Toshimitsu , Ishii Hideki , Obokata Masaru
Published: March 2022

More than half of patients with heart failure have a preserved ejection fraction (HFpEF). The prevalence of HFpEF has been increasing worldwide and is expected to increase further, making it an important health-care problem. The diagnosis of HFpEF is straightforward in the presence of obvious objective signs of congestion; however, it is challenging in patients presenting with a low degree of congestion because abnormal elevation in intracardiac pressures may occur only during physiological stress conditions, such as during exercise. On the basis of this hemodynamic background, current consensus guidelines have emphasized the importance of exercise stress testing to reveal abnormalities during exercise, and exercise stress echocardiography (i.e., diastolic stress echocardiography) may be used as an initial diagnostic approach to HFpEF owing to its noninvasive nature and wide availability. However, evidence supporting the use of this method remains limited and many knowledge gaps exist with respect to diastolic stress echocardiography. This review summarizes the current understanding of the use of diastolic stress echocardiography in the diagnostic evaluation of HFpEF and discusses its strengths and limitations to encourage future studies on this subject.
Comparison of the Mid-Term Outcomes of Robotic Magnetic Navigation-Guided Radiofrequency Ablation versus Cryoballoon Ablation for Persistent Atrial Fibrillation
Authors: Li Xiang , Bao Yangyang , Jia Kangni , Zhang Ning , Lin Changjian , Wei Yue , Xie Yun , Luo Qingzhi , Ling Tianyou , Chen Kang , Pan Wenqi , Wu Liqun , Jin Qi
Published: March 2022

Introduction: Currently, numerous ablation techniques are available for atrial fibrillation (AF), in addition to manual radio frequency ablation. The aim of this prospective, non-randomized concurrent controlled trial was to compare the mid-term efficacy and procedural outcomes of persistent AF (PerAF) using cryoballoon (CB) and robotic magnetic navigation (RMN). Methods: Two hundred PerAF patients were assigned, in a 1:1 ratio, to undergo catheter ablation using RMN (RMN group) or CB (CB group). The primary endpoint was freedom from AF recurrence following a 3-month period after the index ablation. The secondary endpoint was peri-procedural outcomes, including the total procedure time, left atrial procedure time, fluoroscopy time, and fluoroscopy dose. The Two-step cluster analysis was used to determine the efficacy of RMN and CB between the different groups. The Cox proportional hazard model and restricted cubic spline were used to determine predictors for AF recurrence. Results: At the mean follow-up of 28.1 ± 9.7 months, the primary endpoint was achieved in 71 PerAF patients in the RMN group and in 62 PerAF patients in the CB group (71% vs. 62%, p = 0.158). Compared with CB, RMN-guided ablation led to a longer procedure time (p < 0.001), but with less radiation (p < 0.001). Cluster analysis returned two clusters of patients and RMN was favorable for one cluster (p = 0.037), in which more patients presented with diabetes mellitus and smaller left atria. Conclusions: For patients with PerAF, CB is generally equivalent to RMN-guided ablation with regard to overall efficacy. RMN-guided ablation could be favorable in specific patient populations presenting with diabetes mellitus and smaller left atria.
Sex-Related Effects on Cardiac Development and Disease
Authors: Siokatas Georgios , Papatheodorou Ioanna , Daiou Angeliki , Lazou Antigone , Hatzistergos Konstantinos E. , Kararigas Georgios
Published: March 2022

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality. Interestingly, male and female patients with CVD exhibit distinct epidemiological and pathophysiological characteristics, implying a potentially important role for primary and secondary sex determination factors in heart development, aging, disease and therapeutic responses. Here, we provide a concise review of the field and discuss current gaps in knowledge as a step towards elucidating the “sex determination–heart axis”. We specifically focus on cardiovascular manifestations of abnormal sex determination in humans, such as in Turner and Klinefelter syndromes, as well as on the differences in cardiac regenerative potential between species with plastic and non-plastic sexual phenotypes. Sex-biased cardiac repair mechanisms are also discussed with a focus on the role of the steroid hormone 17β-estradiol. Understanding the “sex determination–heart axis” may offer new therapeutic possibilities for enhanced cardiac regeneration and/or repair post-injury.
Carpal Tunnel Syndrome and Diabetes—A Comprehensive Review
Authors: Zimmerman Malin , Gottsäter Anders , Dahlin Lars B.
Published: March 2022

Carpal tunnel syndrome (CTS) is the most common compression neuropathy in the general population and is frequently encountered among individuals with type 1 and 2 diabetes. The reason(s) why a peripheral nerve trunk in individuals with diabetes is more susceptible to nerve compression is still not completely clarified, but both biochemical and structural changes in the peripheral nerve are probably implicated. In particular, individuals with neuropathy, irrespective of aetiology, have a higher risk of peripheral nerve compression disorders, as reflected among individuals with diabetic neuropathy. Diagnosis of CTS in individuals with diabetes should be carefully evaluated; detailed case history, thorough clinical examination, and electrophysiological examination is recommended. Individuals with diabetes and CTS benefit from surgery to the same extent as otherwise healthy individuals with CTS. In the present review, we describe pathophysiological aspects of the nerve compression disorder CTS in relation to diabetes, current data contributing to the explanation of the increased risk for CTS in individuals with diabetes, as well as diagnostic methods, treatment options, and prognosis of CTS in diabetes.
The Obesity Paradox in Real-World Nation-Wide Cohort of Patients Admitted for a Stroke in the U.S.
Authors: Rozen Guy , Elbaz-Greener Gabby , Margolis Gilad , Marai Ibrahim , Heist Edwin K. , Ruskin Jeremy N. , Carasso Shemy , Roguin Ariel , Birati Edo Y. , Amir Offer
Published: March 2022

Background: Obesity has been associated with increased incidence and severity of various cardiovascular risk factors and increased risk for stroke. However, the evidence of its effect on outcomes in stroke victims have been equivocal. We aimed to investigate the distribution of BMI in a nation-wide cohort of individuals, admitted for a stroke, and the relationship between BMI and in-hospital mortality. Methods: Data from the U.S. National Inpatient Sample (NIS) was collected, to identify hospitalizations for stroke, between October 2015 and December 2016. The patients were sub-divided into six groups based on their BMI: underweight, normal weight, overweight, obese I, obese II and extremely obese groups. Various sociodemographic and clinical parameters were gathered, and incidence of mortality and the length of hospital stay were analyzed. Multivariable analysis was performed to identify independent predictors of in-hospital mortality. Results: A weighted total of 84,185 hospitalizations for stroke were included in the analysis. The approximate mean patients aged was 65.5 ± 31 years, the majority being female (55.3%) and white (63.1%). The overall in-hospital mortality during the study period was 3.6%. A reverse J-shaped relationship between the body mass index and in-hospital mortality was documented, while patients with elevated BMI showed significantly lower in-hospital mortality compared to the underweight and normal weight study participants, 2.8% vs. 7.4%, respectively, p < 0.001. Age and several comorbidities, as well as the Deyo Comorbidity Index, were found to predict mortality in a multivariable analysis. Conclusion: A reverse J-shaped relationship between body mass index and in-hospital mortality was documented in patients admitted for a stroke in the U.S. during the study period. The above findings support the existence of an “obesity paradox” in patients hospitalized following a stroke, similar to that described in other cardiovascular conditions.
Coronavirus Disease Transmission Prevented in an Endoscopy Unit with Universal Protective Measures and No Systematic Preprocedural Testing
Authors: Guilabert Lucía , Aparicio José Ramón , Medina-Prado Lucía , Rodríguez-Díaz Juan Carlos , Gomis María Luisa , Chico-Sánchez Pablo , Sánchez-Payá José , Jover Rodrigo
Published: March 2022

Background and aims: Even after two years of pandemic, there are still uncertainties on how to proceed when we schedule endoscopic procedures. During the COVID-19 pandemic, some scientific societies recommended universal preprocedural testing for all patients. However, other societies recommended against and considered enough to maintain strict infection control strategies. Our aim was to evaluate this approach in order to see if it was safe for both patients and healthcare workers to proceed with the endoscopies without performing a systematic PCR on all patients. Methods: Retrospective chart review of all patients undergoing endoscopy without preprocedural COVID testing at our center from March 2020 to May 2021. PCR tests performed in the patients receiving an endoscopic procedure were analyzed, and patients who tested positive between 14 days before and after the endoscopic procedure were selected. The registry of the endoscopy unit members participating in these procedures was also analyzed. Results: A total of 10,132 procedures were performed in the unit with 26 patients infected with SARS-CoV-2. Nineteen of these procedures were performed in patients with unknown SARS-CoV-2 carrier status. In 23 (88.5%) cases, transmission occurred through social or familial contact, and in 3 (11.5%), transmission occurred in the hospital. Four health care workers became infected during this period and none of them were related to the endoscopic procedures performed in patients with COVID-19. Conclusions: SARS-CoV-2 positive testing in asymptomatic ambulatory patients is rare and the adequate use of individual protective measures emerges as the main way to control the spread of COVID-19 infection in endoscopy centers.
Application of Translaryngeal Ultrasound (TLUS) in Patients with Neck Surgery—A Single-Centre, Prospective Cohort Study on Technique Evaluation
Authors: Wolff Sylwia , Gałązka Adam , Borkowski Rafał , Gorzelnik Anna , Dedecjus Marek
Published: March 2022

Purpose: The primary objective of this study was to assess the value of translaryngeal ultrasound (TLUS) in assessing vocal fold (VF) function in patients after thyroid, parathyroid and neck lymph node surgery. Methods: A total of 219 patients that underwent 230 surgical procedures were enrolled in this prospective study. The study was conducted from October 2020 to October 2021. Patients’ VFs were analysed independently with TLUS and laryngoscopy before and after the surgery. Various TLUS variables, such as vocal folds displacement velocity (VFDV), arytenoids symmetry and angle between VFs, were measured. The questionnaire evaluating discomfort caused to patients by both methods was conducted. Results: Of the 230 surgeries in this study, 85% were from oncological indications. The incidence of RLN injury was 10.4%. The accuracy of TLUS compared to laryngoscopy was 98.3%, with sensitivity 98.1%, specificity 100%, PPV 100% and NPV 83.3%. Laryngoscopy was found to cause significantly more discomfort than TLUS. VF visibility was lower in men; smokers; and patients with higher BMI (32 vs. 28 kg/m2), multifocal cancer, higher left lobe volume and higher fT3 levels. Arytenoid symmetry VFDV was lower for “e” and “i” right side and “i” left side in injured/disabled VFs/RLN. Conclusions: TLUS can be an excellent and non-invasive method of VF evaluation in most patients. There are some technical aspects that can improve its accuracy. Sometimes, RLN injury after the surgery, especially among oncological patients, is unavoidable. Therefore, it is vital to diagnose dysphonia early with convenient methods, such as TLUS.
Coronary Malperfusion Secondary to Acute Type A Aortic Dissection: Surgical Management Based on a Modified Neri Classification
Authors: Tong Guang , Wu Jinlin , Chen Zerui , Zhuang Donglin , Zhao Shuang , Liu Yaorong , Yang Yongchao , Liang Zhichao , Fan Ruixin , Sun Zhongchan , Sun Tucheng
Published: March 2022

Background: Coronary malperfusion (CM) secondary to acute type A aortic dissection (ATAAD) is considered rare but has a high mortality rate. This study examined the incidence, management, and outcomes of patients with CM secondary to ATAAD and proposes a modified Neri classification. Methods: Between 2015 and 2020, out of 1018 patients who underwent surgical repair for ATAAD, 137 presented with CM, including 68 (49.6%), 43 (31.3%), and 15 (10.9%) with Neri types A, B, and C, respectively, and 11 (8.0%) with coronary orifice intimal tear (COIT), which we consider a novel category. Results: The occurrence rate of CM was 13.4%. CM was associated with higher in-hospital mortality (18.2% vs. 7.8%, p < 0.001). For Neri type A (98.5%) and most type B lesions (72.1%), coronary repair was adequate. Coronary artery bypass grafting (CABG) was necessary for type B patients unsuited for repair (23.2%) and for all type C patients (100%). Repair of COIT was possible (45.5%). The in-hospital mortality rates differed significantly among the four lesion groups (p = 0.006). Conclusions: The occurrence of CM secondary to ATAAD may be more frequent than previously reported. Surgical management based on lesion classification achieved acceptable outcomes. Repair was adequate for Neri type A and most type B lesions. Other type B and type C lesions could be treated by CABG. Coronary orifice intimal tear is a unique set of lesions, for which orifice repair was also possible.
Predictors of Serological Response to SARS-CoV-2 Vaccination in Kidney Transplant Patients: Baseline Characteristics, Immunosuppression, and the Role of IMPDH Monitoring
Authors: Liefeldt Lutz , Glander Petra , Klotsche Jens , Straub-Hohenbleicher Henriette , Budde Klemens , Eberspächer Bettina , Friedersdorff Frank , Halleck Fabian , Hambach Pia , Hofmann Jörg , Koch Nadine , Schmidt Danilo , Schrezenmeier Eva , Seelow Evelyn , Weber Ulrike , Zukunft Bianca , Eckardt Kai-Uwe , Choi Mira , Bachmann Friederike , Waiser Johannes
Published: March 2022

Immunosuppression increases the risk of severe coronavirus disease 2019 (COVID-19). Morbidity and mortality of this disease in kidney transplant patients are higher than in the general population. As the vaccination response of transplant patients is weak, serological monitoring was performed. In this cohort study, we analyzed the determinants of vaccination response. All patients had no history of COVID-19. With anti-spike IgG monitoring, 148 responders and 415 non-responders were identified. We compared both groups using multivariate analyses of the cohort and a sub-cohort of mycophenolic-acid-treated patients. We investigated the influence of patient characteristics, immunosuppression, and erythrocyte inosine monophosphate dehydrogenase (IMPDH) activity. In responders, the time after transplantation was longer (13.5 vs. 8.5 years), the glomerular filtration rate was higher (56.9 vs. 47.8 mL/min/1.73 m2), and responders were younger (53.0 vs. 57.4 years). Heterologous vaccination was more effective than homologous vaccination. Calcineurin inhibitors plus mycophenolate reduced the seroconversion rate. No seroconversion was observed in belatacept patients. In mycophenolate-treated patients, IMPDH activity was a significantly better predictor of response than mycophenolate dose (AUC 0.84 vs. 0.62, p < 0.001). Immunosuppression strongly affects vaccine response. Modifications to immunosuppression should be considered in order to facilitate this response. Erythrocyte IMPDH activity can be used to guide mycophenolate treatment.
Measuring Factor XIII Inhibitors in Patients with Factor XIII Deficiency: A Case Report and Systematic Review of Current Practices in Japan
Authors: Amano Shiho , Oka Kohei , Sato Yutaka , Sano Chiaki , Ohta Ryuichi
Published: March 2022

Factor XIII (FXIII) deficiency is a rare but serious coagulopathy. FXIII is critical in blood coagulation, and FXIII deficiencies can lead to uncontrolled or spontaneous bleeding. FXIII deficiencies can be congenital or acquired; acquired FXIII deficiency can be categorized as autoimmune and non-autoimmune. Immunological tests to measure FXIII inhibitors are required to diagnose acquired FXIII deficiency; however, appropriate test facilities are limited, which increases the turnaround time of these tests. In the case of critical bleeding, delayed test results may worsen prognosis due to delayed treatment. Here, we report a case of acquired FXIII deficiency, followed by a review of FXIII deficiency cases in Japan. We performed a systematic review to investigate the present conditions of the diagnosis and treatment of FXIII deficiency, including the measurement of FXIII inhibitors in Japan. FXIII inhibitor testing was only performed in 29.7 of acquired FXIII deficiency cases. Clinical departments other than internal medicine and pediatrics were often involved in medical treatment at the time of onset. Therefore, it is important for doctors in clinical departments other than internal medicine and pediatrics to consider FXIII deficiency and perform FXIII inhibitor testing when examining patients with prolonged bleeding of unknown cause or persistent bleeding after trauma.
Comparison of Radiation Exposure between Endoscopic Ultrasound-Guided Hepaticogastrostomy and Hepaticogastrostomy with Antegrade Stenting
Authors: Takenaka Mamoru , Rehani Madan M. , Hosono Makoto , Yamazaki Tomohiro , Omoto Shunsuke , Minaga Kosuke , Kamata Ken , Yamao Kentaro , Hayashi Shiro , Nishida Tsutomu , Kudo Masatoshi
Published: March 2022

Fluoroscopy forms an essential part of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) and hepaticogastrostomy with antegrade stenting (EUS-HGAS). To date, no study has assessed and compared radiation exposure between EUS-HGS and EUS-HGAS. This study aimed to compare the radiation exposure parameters between EUS-HGS and EUS-HGAS. This retrospective single-center cohort study included consecutive patients who underwent EUS-HGS or EUS-HGAS from October 2017 to March 2019. The air kerma (AK: mGy), kerma–area product (KAP: Gycm2), fluoroscopy time (FT: min), and procedure time (PT: min) were assessed and compared between the two procedures. Altogether, 45 and 24 patients underwent EUS-HGS and EUS-HGAS, respectively. The median AK, KAP, FT, and PT were higher in the EUS-HGAS group than in the EUS-HGS group. A comparison revealed no difference in the technical success rate, complications rate, adverse event occurrence rate, and re-intervention rate between both procedures. This is the first report in which radiation exposure was used as a comparative parameter between EUS-HGS and EUS-HGAS. This study revealed that radiation exposure is significantly higher in EUS-HGAS than in EUS-HGS. Increased awareness on radiation exposure is warranted among gastroenterologists so that they choose the procedure with lower radiation exposure in cases where both procedures are indicated.
Repair of Mitral Valves with Severe Annular Dilatation and Abundant Leaflet Tissue Using a Prosthetic Ring with a Large Anterior-Posterior Diameter
Authors: Sideris Konstantinos , Burri Melchior , Bordne Joanna , Vitanova Keti , Voss Bernhard , Krane Markus , Lange Rüdiger
Published: March 2022

Backround: Mitral valve (MV) repair in the case of a large anterior-posterior diameter and redundant valve tissue remains challenging and favors repair with a ring that exhibits a large anterior-posterior diameter. Compared to other available rings, the Medtronic Simulus annuloplasty ring shows the largest anterior-posterior diameter. This study reports for the first time mid-term results using this annuloplasty ring. Methods: Between 11/2015 and 12/2019, a total of 378 patients underwent MV repair for degenerative mitral regurgitation using the Medtronic Simulus ring, according to the following selection criteria: large MV annuli, abundant leaflet tissue (i.e., Barlow disease), and risk for SAM. Results: Overall survival after 5 years was 90.8 ± 4.6%. Five patients required valve-related reoperations because of ring dehiscence (n = 1), progression of native valve disease (n = 2), dehiscence of quadrangular resection suture (n = 1), and endocarditis (n = 1). The cumulative incidence of valve-related reoperation at 5 years was 1.3 ± 0.5%. At latest follow-up, echocardiography demonstrated excellent valve function with no/mild MR in 299 patients (94.6%). Two patients (0.6%) had more than moderate MR. No patient developed SAM after repair. Conclusion: Repair of MV with large annuli and abundant leaflet tissue with the Medtronic Simulus annuloplasty ring shows excellent mid-term results regarding reoperation rates and recurrent MR.
Interventional Endoscopy for Palliation of Luminal Gastrointestinal Obstructions in Management of Cancer: Practical Guide for Oncologists
Authors: Kim Matthew , Rai Mandip , Teshima Christopher
Published: March 2022

Self-expanding metal stents placed during endoscopy are increasingly the first-line treatment for luminal obstruction caused by esophageal, gastroduodenal, and colorectal malignancies in patients who are not candidates for definitive surgical resection. In this review, we provide a practical guide for clinicians to optimise patient and procedure selection for endoscopic stenting in malignant gastrointestinal obstructions. The role of endoscopic stenting in each of the major anatomical systems (esophageal, gastroduodenal, and colorectal) is presented with regard to pre-procedural patient evaluation, procedural techniques, clinical outcomes, and potential complications, as well as post-procedure aftercare.