bluuebunny/crossref_metadata_2025 huggingface dataset:
The Modulation of SCO2730/31 Copper Chaperone/Transporter Orthologue Expression Enhances Secondary Metabolism in Streptomycetes
Authors: González-Quiñónez Nathaly , Gutiérrez-Del-Río Ignacio , García-Cancela Paula , Fernández-García Gemma , Alonso-Fernández Sergio , Yagüe Paula , Pérez-Valero Álvaro , Montes-Bayón María , Lombó Felipe , Manteca Ángel
Published: September 2021

Streptomycetes are important biotechnological bacteria that produce several clinically bioactive compounds. They have a complex development, including hyphae differentiation and sporulation. Cytosolic copper is a well-known modulator of differentiation and secondary metabolism. The interruption of the Streptomyces coelicolor SCO2730 (copper chaperone, SCO2730::Tn5062 mutant) blocks SCO2730 and reduces SCO2731 (P-type ATPase copper export) expressions, decreasing copper export and increasing cytosolic copper. This mutation triggers the expression of 13 secondary metabolite clusters, including cryptic pathways, during the whole developmental cycle, skipping the vegetative, non-productive stage. As a proof of concept, here, we tested whether the knockdown of the SCO2730/31 orthologue expression can enhance secondary metabolism in streptomycetes. We created a SCO2730/31 consensus antisense mRNA from the sequences of seven key streptomycetes, which helped to increase the cytosolic copper in S. coelicolor, albeit to a lower level than in the SCO2730::Tn5062 mutant. This antisense mRNA affected the production of at least six secondary metabolites (CDA, 2-methylisoborneol, undecylprodigiosin, tetrahydroxynaphtalene, α-actinorhodin, ε-actinorhodin) in the S. coelicolor, and five (phenanthroviridin, alkylresorcinol, chloramphenicol, pikromycin, jadomycin G) in the S. venezuelae; it also helped to alter the S. albus metabolome. The SCO2730/31 consensus antisense mRNA designed here constitutes a tool for the knockdown of SCO2730/31 expression and for the enhancement of Streptomyces’ secondary metabolism.
Differential Regulation of Interferon Signaling Pathways in CD4+ T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype
Authors: Alhamdan Fahd , Marsh Leigh M. , Pedersen Frauke , Alhamwe Bilal Alashkar , Thölken Clemens , Pfefferle Petra Ina , Bahmer Thomas , Greulich Timm , Potaczek Daniel P. , Garn Holger
Published: September 2021

In the era of personalized medicine, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as asthma phenotypes including obesity-associated asthma, are urgently needed. Peripheral blood was drawn from 10 obese, non-atopic asthmatic adults with a high body mass index (BMI; 36.67 ± 6.90); 10 non-obese, non-atopic asthmatic adults with normal BMI (23.88 ± 2.73); and 10 healthy controls with normal BMI (23.62 ± 3.74). All asthmatic patients were considered to represent a low type-2 asthma phenotype according to selective clinical parameters. RNA sequencing (RNA-Seq) was conducted on peripheral blood CD4+ T cells. Thousands of differentially expressed genes were identified in both asthma groups compared with heathy controls. The expression of interferon (IFN)-stimulated genes associated with IFN-related signaling pathways was specifically affected in obese asthmatics, while the gap junction and G protein-coupled receptor (GPCR) ligand binding pathways were enriched in both asthma groups. Furthermore, obesity gene markers were also upregulated in CD4+ T cells from obese asthmatics compared with the two other groups. Additionally, the enriched genes of the three abovementioned pathways showed a unique correlation pattern with various laboratory and clinical parameters. The specific activation of IFN-related signaling and viral infection pathways might provide a novel view of the molecular mechanisms associated with the development of the low type-2 obesity-associated asthma phenotype, which is a step ahead in the development of new stratified therapeutic approaches.
Selected Essential and Toxic Chemical Elements in Hypothyroidism—A Literature Review (2001–2021)
Authors: Błażewicz Anna , Wiśniewska Patrycja , Skórzyńska-Dziduszko Katarzyna
Published: September 2021

Thyroid hormones are known for controlling metabolism of lipids, carbohydrates, proteins, minerals, and electrolytes and for regulating body temperature. Normal thyroid status depends on the chemical/elemental composition of body fluids and tissues, which changes depending on physiological state, lifestyle and environment. A deficiency or excess of certain essential chemical elements (selenium, zinc, copper, iron or fluorine) or exposure to toxic (cadmium or lead) or potentially toxic elements (manganese or chromium) interacts with thyroid hormone synthesis and may disturb thyroid homeostasis. In our review, accessible databases (Scopus, PubMed and Web of Science) were searched for articles from 2001–2021 on the influence of selected chemical elements on the development of hypothyroidism. Our review adopted some of the strengths of a systematic review. After non-eligible reports were rejected, 29 remaining articles were reviewed. The review found that disruption of the physiological levels of elements in the body adversely affects the functioning of cells and tissues, which can lead to the development of disease.
Oxidative Folding of Proteins: The “Smoking Gun” of Glutathione
Authors: Bocedi Alessio , Cattani Giada , Gambardella Giorgia , Schulte Linda , Schwalbe Harald , Ricci Giorgio
Published: September 2021

Glutathione has long been suspected to be the primary low molecular weight compound present in all cells promoting the oxidative protein folding, but twenty years ago it was found “not guilty”. Now, new surprising evidence repeats its request to be the “smoking gun” which reopens the criminal trial revealing the crucial involvement of this tripeptide.
Biomarkers for Ehlers-Danlos Syndromes: There Is a Role?
Authors: Caliogna Laura , Guerrieri Viviana , Annunziata Salvatore , Bina Valentina , Brancato Alice Maria , Castelli Alberto , Jannelli Eugenio , Ivone Alessandro , Grassi Federico Alberto , Mosconi Mario , Pasta Gianluigi
Published: September 2021

Ehlers-Danlos syndromes (EDS) are an inherited heterogeneous group of connective tissue disorders characterized by an abnormal collagen synthesis affecting skin, ligaments, joints, blood vessels, and other organs. It is one of the oldest known causes of bruising and bleeding, and it was described first by Hippocrates in 400 BC. In the last years, multiple gene variants involved in the pathogenesis of specific EDS subtypes have been identified; moreover, new clinical diagnostic criteria have been established. New classification models have also been studied in order to differentiate overlapping conditions. Moreover, EDS shares many characteristics with other similar disorders. Although distinguishing between these seemingly identical conditions is difficult, it is essential in ensuring proper patient care. Currently, there are many genetic and molecular studies underway to clarify the etiology of some variants of EDS. However, the genetic basis of the hypermobile type of EDS (hEDS) is still unknown. In this review, we focused on the study of two of the most common forms of EDS—classic and hypermobile—by trying to identify possible biomarkers that could be of great help to confirm patients’ diagnosis and their follow up.
The Effect of Resveratrol on the Cardiovascular System from Molecular Mechanisms to Clinical Results
Authors: Gal Roland , Deres Laszlo , Toth Kalman , Halmosi Robert , Habon Tamas
Published: September 2021

Cardiovascular diseases are the leading causes of death worldwide. The cardioprotective effects of natural polyphenols such as resveratrol (3,5,4-trihydroxystilbene) have been extensively investigated throughout recent decades. Many studies of RES have focused on its favorable effects on pathological conditions related to cardiovascular diseases and their risk factors. The aim of this review was to summarize the wide beneficial effects of resveratrol on the cardiovascular system, including signal transduction pathways of cell longevity, energy metabolism of cardiomyocytes or cardiac remodeling, and its anti-inflammatory and antioxidant properties. In addition, this paper discusses the significant preclinical and human clinical trials of recent years with resveratrol on cardiovascular system. Finally, we present a short overview of antiviral and anti-inflammatory properties and possible future perspectives on RES against COVID-19 in cardiovascular diseases.
Adipose Tissue-Derived Stromal Cells Alter the Mechanical Stability and Viscoelastic Properties of Gelatine Methacryloyl Hydrogels
Authors: Martinez-Garcia Francisco Drusso , Valk Martine Margaretha , Sharma Prashant Kumar , Burgess Janette Kay , Harmsen Martin Conrad
Published: September 2021

The extracellular matrix provides mechanical cues to cells within it, not just in terms of stiffness (elasticity) but also time-dependent responses to deformation (viscoelasticity). In this work, we determined the viscoelastic transformation of gelatine methacryloyl (GelMA) hydrogels caused by adipose tissue-derived stromal cells (ASCs) through mathematical modelling. GelMA-ASCs combination is of interest to model stem cell-driven repair and to understand cell-biomaterial interactions in 3D environments. Immortalised human ASCs were embedded in 5%, 10%, and 15% (w/v) GelMA hydrogels and evaluated for 14 d. GelMA had a concentration-dependent increase in stiffness, but cells decreased this stiffness over time, across concentrations. Viscoelastic changes in terms of stress relaxation increased progressively in 5% GelMA, while mathematical Maxwell analysis showed that the relative importance (Ri) of the fastest Maxwell elements increased proportionally. The 10% GelMA only showed differences at 7 d. In contrast, ASCs in 15% GelMA caused slower stress relaxation, increasing the Ri of the slowest Maxwell element. We conclude that GelMA concentration influenced the stiffness and number of Maxwell elements. ASCs changed the percentage stress relaxation and Ri of Maxwell elements transforming hydrogel viscoelasticity into a more fluid environment over time. Overall, 5% GelMA induced the most favourable ASC response.
Membrane Interactions of Latarcins: Antimicrobial Peptides from Spider Venom
Authors: Wadhwani Parvesh , Sekaran Saiguru , Strandberg Erik , Bürck Jochen , Chugh Archana , Ulrich Anne S.
Published: September 2021

A group of seven peptides from spider venom with diverse sequences constitute the latarcin family. They have been described as membrane-active antibiotics, but their lipid interactions have not yet been addressed. Using circular dichroism and solid-state 15N-NMR, we systematically characterized and compared the conformation and helix alignment of all seven peptides in their membrane-bound state. These structural results could be correlated with activity assays (antimicrobial, hemolysis, fluorescence vesicle leakage). Functional synergy was not observed amongst any of the latarcins. In the presence of lipids, all peptides fold into amphiphilic α-helices as expected, the helices being either surface-bound or tilted in the bilayer. The most tilted peptide, Ltc2a, possesses a novel kind of amphiphilic profile with a coiled-coil-like hydrophobic strip and is the most aggressive of all. It indiscriminately permeabilizes natural membranes (antimicrobial, hemolysis) as well as artificial lipid bilayers through the segregation of anionic lipids and possibly enhanced motional averaging. Ltc1, Ltc3a, Ltc4a, and Ltc5a are efficient and selective in killing bacteria but without causing significant bilayer disturbance. They act rather slowly or may even translocate towards intracellular targets, suggesting more subtle lipid interactions. Ltc6a and Ltc7, finally, do not show much antimicrobial action but can nonetheless perturb model bilayers.
BH3 Mimetics in Hematologic Malignancies
Authors: Klener Pavel , Sovilj Dana , Renesova Nicol , Andera Ladislav
Published: September 2021

Hematologic malignancies (HM) comprise diverse cancers of lymphoid and myeloid origin, including lymphomas (approx. 40%), chronic lymphocytic leukemia (CLL, approx. 15%), multiple myeloma (MM, approx. 15%), acute myeloid leukemia (AML, approx. 10%), and many other diseases. Despite considerable improvement in treatment options and survival parameters in the new millennium, many patients with HM still develop chemotherapy‑refractory diseases and require re-treatment. Because frontline therapies for the majority of HM (except for CLL) are still largely based on classical cytostatics, the relapses are often associated with defects in DNA damage response (DDR) pathways and anti-apoptotic blocks exemplified, respectively, by mutations or deletion of the TP53 tumor suppressor, and overexpression of anti-apoptotic proteins of the B-cell lymphoma 2 (BCL2) family. BCL2 homology 3 (BH3) mimetics represent a novel class of pro-apoptotic anti-cancer agents with a unique mode of action—direct targeting of mitochondria independently of TP53 gene aberrations. Consequently, BH3 mimetics can effectively eliminate even non-dividing malignant cells with adverse molecular cytogenetic alterations. Venetoclax, the nanomolar inhibitor of BCL2 anti-apoptotic protein has been approved for the therapy of CLL and AML. Numerous venetoclax-based combinatorial treatment regimens, next-generation BCL2 inhibitors, and myeloid cell leukemia 1 (MCL1) protein inhibitors, which are another class of BH3 mimetics with promising preclinical results, are currently being tested in several clinical trials in patients with diverse HM. These pivotal trials will soon answer critical questions and concerns about these innovative agents regarding not only their anti-tumor efficacy but also potential side effects, recommended dosages, and the optimal length of therapy as well as identification of reliable biomarkers of sensitivity or resistance. Effective harnessing of the full therapeutic potential of BH3 mimetics is a critical mission as it may directly translate into better management of the aggressive forms of HM and could lead to significantly improved survival parameters and quality of life in patients with urgent medical needs.
Endothelial Colony-Forming Cells Dysfunctions Are Associated with Arterial Hypertension in a Rat Model of Intrauterine Growth Restriction
Authors: Simoncini Stephanie , Coppola Hanna , Rocca Angela , Bachmann Isaline , Guillot Estelle , Zippo Leila , Dignat-George Françoise , Sabatier Florence , Bedel Romain , Wilson Anne , Rosenblatt-Velin Nathalie , Armengaud Jean-Baptiste , Menétrey Steeve , Peyter Anne-Christine , Simeoni Umberto , Yzydorczyk Catherine
Published: September 2021

Infants born after intrauterine growth restriction (IUGR) are at risk of developing arterial hypertension at adulthood. The endothelium plays a major role in the pathogenesis of hypertension. Endothelial colony-forming cells (ECFCs), critical circulating components of the endothelium, are involved in vasculo-and angiogenesis and in endothelium repair. We previously described impaired functionality of ECFCs in cord blood of low-birth-weight newborns. However, whether early ECFC alterations persist thereafter and could be associated with hypertension in individuals born after IUGR remains unknown. A rat model of IUGR was induced by a maternal low-protein diet during gestation versus a control (CTRL) diet. In six-month-old offspring, only IUGR males have increased systolic blood pressure (tail-cuff plethysmography) and microvascular rarefaction (immunofluorescence). ECFCs isolated from bone marrow of IUGR versus CTRL males displayed a decreased proportion of CD31+ versus CD146+ staining on CD45− cells, CD34 expression (flow cytometry, immunofluorescence), reduced proliferation (BrdU incorporation), and an impaired capacity to form capillary-like structures (Matrigel test), associated with an impaired angiogenic profile (immunofluorescence). These dysfunctions were associated with oxidative stress (increased superoxide anion levels (fluorescent dye), decreased superoxide dismutase protein expression, increased DNA damage (immunofluorescence), and stress-induced premature senescence (SIPS; increased beta-galactosidase activity, increased p16INK4a, and decreased sirtuin-1 protein expression). This study demonstrated an impaired functionality of ECFCs at adulthood associated with arterial hypertension in individuals born after IUGR.
Endothelium-Derived Hyperpolarizing Factor (EDHF) Mediates Acetylsalicylic Acid (Aspirin) Vasodilation of Pregnant Rat Mesenteric Arteries
Authors: Helgadóttir Helga , Tropea Teresa , Gizurarson Sveinbjörn , Mandalà Maurizio
Published: September 2021

Acetylsalicylic acid (aspirin) exhibits a broad range of activities, including analgesic, antipyretic, and antiplatelet properties. Recent clinical studies also recommend aspirin prophylaxis in women with a high risk of pre-eclampsia, a major complication of pregnancy characterized by hypertension. We investigated the effect of aspirin on mesenteric resistance arteries and found outdiscovered the molecular mechanism underlying this action. Aspirin (10−12–10−6 M) was tested on pregnant rat mesenteric resistance arteries by a pressurized arteriography. Aspirin was investigated in the presence of several inhibitors of: (a) nitric oxide synthase (L-NAME 2 × 10−4 M); (b) cyclooxygenase (Indomethacin, 10−5 M); (c) Ca2+-activated K+ channels (Kca): small conductance (SKca, Apamin, 10−7 M), intermediate conductance (IKca, TRAM34, 10−5 M), and big conductance (BKca, paxilline, 10−5 M); and (d) endothelial-derived hyperpolarizing factor (high KCl, 80 mM). Aspirin caused a concentration-dependent vasodilation. Aspirin-vasodilation was abolished by removal of endothelium or by high KCl. Furthermore, preincubation with either apamin plus TRAM-34 or paxillin significantly attenuated aspirin vasodilation (p < 0.05). For the first time, we showed that aspirin induced endothelium-dependent vasodilation in mesenteric resistance arteries through the endothelial-derived hyperpolarizing factor (EDHF) and calcium-activated potassium channels. By activating this molecular mechanism, aspirin may lower peripheral vascular resistance and be beneficial in pregnancies complicated by hypertension.
Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia
Authors: Cairns Lauren V. , Lappin Katrina M. , Mutch Alexander , Ali Ahlam , Matchett Kyle B. , Mills Ken I.
Published: September 2021

Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the malignant transformation of myeloid precursor cells with impaired differentiation. Standard therapy for paediatric AML has remained largely unchanged for over four decades and, combined with inadequate understanding of the biology of paediatric AML, has limited the progress of targeted therapies in this cohort. In recent years, the search for novel targets for the treatment of paediatric AML has accelerated in parallel with advanced genomic technologies which explore the mutational and transcriptional landscape of this disease. Exploiting the large combinatorial space of existing drugs provides an untapped resource for the identification of potential combination therapies for the treatment of paediatric AML. We have previously designed a multiplex screening strategy known as Multiplex Screening for Interacting Compounds in AML (MuSICAL); using an algorithm designed in-house, we screened all pairings of 384 FDA-approved compounds in less than 4000 wells by pooling drugs into 10 compounds per well. This approach maximised the probability of identifying new compound combinations with therapeutic potential while minimising cost, replication and redundancy. This screening strategy identified the triple combination of glimepiride, a sulfonylurea; pancuronium dibromide, a neuromuscular blocking agent; and vinblastine sulfate, a vinca alkaloid, as a potential therapy for paediatric AML. We envision that this approach can be used for a variety of disease-relevant screens allowing the efficient repurposing of drugs that can be rapidly moved into the clinic.
Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal
Authors: Freeman David W. , Rodrigues Sousa Elisa , Karkampouna Sofia , Zoni Eugenio , Gray Peter C. , Salomon David S. , Kruithof-de Julio Marianna , Spike Benjamin T.
Published: September 2021

There exists a set of factors termed oncofetal proteins that play key roles in ontogeny before they decline or disappear as the organism’s tissues achieve homeostasis, only to then re-emerge in cancer. Although the unique therapeutic potential presented by such factors has been recognized for more than a century, their clinical utility has yet to be fully realized1. This review highlights the small signaling protein CRIPTO encoded by the tumor derived growth factor 1 (TDGF1/Tdgf1) gene, an oft cited oncofetal protein whose presence in the cancer literature as a tumor promoter, diagnostic marker and viable therapeutic target continues to grow. We touch lightly on features well established and well-reviewed since its discovery more than 30 years ago, including CRIPTO’s early developmental roles and modulation of SMAD2/3 activation by a selected set of transforming growth factor β (TGF-β) family ligands. We predominantly focus instead on more recent and less well understood additions to the CRIPTO signaling repertoire, on its potential upstream regulators and on new conceptual ground for understanding its mode of action in the multicellular and often stressful contexts of neoplastic transformation and progression. We ask whence it re-emerges in cancer and where it ‘hides’ between the time of its fetal activity and its oncogenic reemergence. In this regard, we examine CRIPTO’s restriction to rare cells in the adult, its potential for paracrine crosstalk, and its emerging role in inflammation and tissue regeneration—roles it may reprise in tumorigenesis, acting on subsets of tumor cells to foster cancer initiation and progression. We also consider critical gaps in knowledge and resources that stand between the recent, exciting momentum in the CRIPTO field and highly actionable CRIPTO manipulation for cancer therapy and beyond.
Spatial Pattern and Influencing Factors of Outward Foreign Direct Investment Enterprises in the Yangtze River Economic Belt of China
Authors: Shi Fei , Xu Haiying , Hsu Wei-Ling , Lee Yee-Chaur , Zhu Juhua
Published: September 2021

This paper studies outward foreign direct investment (OFDI) enterprises in the Yangtze River Economic Belt. Using geographical information system (GIS) spatial analysis and SPSS correlation analysis methods, it analyzes the change in the spatial distribution of OFDI enterprises in 2010, 2014, and 2018. It explores the influencing factors that have an impact on this change. The results show the following: (1) The geographical distribution of OFDI enterprises in the Yangtze River Economic Belt is uneven. In the downstream region, OFDI enterprises have significant advantages in both quantity and quality over those in the mid- and up-stream regions. In recent years, a multi-core spatial pattern has gradually emerged. (2) The factors influencing the spatial distribution of OFDI enterprises have been gradually changing from one dominant factor, i.e., technological innovation capability, to four core factors, namely, urbanization level, economic development level, technological innovation capability, and degree of economic openness. The research results serve as an important reference for future policy adjustment in the Yangtze River Economic Belt. First, the Yangtze River Economic Belt should adjust industrial policies; comprehensively increase the level of OFDI; accelerate the upgrading and transformation of regional industries; and, at the same time, inject vitality into the development of the world economy. Moreover, the downstream region should fully play a leading role in the Yangtze River Economic Belt, especially in encouraging OFDI enterprises to establish global production networks. Meanwhile, enterprises in the upstream region are encouraged to establish regional production networks to accelerate the development of inland open highlands.
Individual Scent-Marks of Nest Entrances in the Solitary Bee, Osmia cornuta (Hymenoptera: Apoidea)
Authors: Frahnert Konrad Sebastian , Seidelmann Karsten
Published: September 2021

The ability to recognize the own nest is a basic skill in nest constructing solitary bees. Osmia cornuta females use a dual mechanism of visual orientation to approach a nest and olfactory verification of the tube when entering it. Occupied tubular cavities were steadily marked by the resident female. Nest marking substances originate from Dufour’s gland and cuticle, enriched by external volatiles. Scent tags were dominated by alkanes and alkenes in a species-specific mixture enriched by small amounts of fatty acid esters, alcohols, and aldehydes. The individual nest tags are sufficiently variable but do not match perfectly with the nesting female. Furthermore, tags are not consistent over time, although females continue in marking. Besides the correct position of the entrance in space, bees have to learn also the bouquet of the used cavity and update their internal template at each visit to recognize their own nest by its actual smell. Due to the dominance of the species-specific hydrocarbon pattern, nest marks may function not only as an occupied sign but may also provide information on the species affiliation and constitution of the nest owner.
Identification of the Short Neuropeptide F and Short Neuropeptide F Receptor Genes and Their Roles of Food Intake in Dendroctonus armandi
Authors: Liu Bin , Fu Danyang , Ning Hang , Tang Ming , Chen Hui
Published: September 2021

The short neuropeptide F (sNPF) is an essential signaling molecule that is evolutionarily conserved and involved in a broad range of physiological functions in the invertebrates, by interacting with sNPF receptors, which belong to G protein-coupled receptors (GPCR). However, the function of sNPF in regulating the food intake of Dendroctonus armandi has been unclear. In this study, we cloned and characterized cDNAs encoding sNPF and sNPF receptor in the D. armandi and made bioinformatics predictions on the deduced amino acid sequences. They had a high degree of similarity to that of Dendroctonus ponderosa. Quantitative real-time reverse transcription PCR (qRT-PCR) revealed that the transcript levels of both sNPF and sNPFR varied across developmental stages and body parts. In addition, the sNPF and sNPFR expression levels were upregulated in starved beetles, and the expression levels recovered after re-feeding. Furthermore, RNAi knockdown by the injection of sNPF and sNPFR dsRNA into beetles significantly increased mortality and reduced their food intake and body weight, and also caused decrease of glycogen and free fatty acid and increase of trehalose. These results indicate that sNPF signaling pathway plays an important role in the regulation of food intake and provides a potential molecular target for the eco-friendly control strategies of this pest.
The Effect of Submaximal Exercise Followed by Short-Term Cold-Water Immersion on the Inflammatory State in Healthy Recreational Athletes: A Cross-Over Study
Authors: Pawłowska Marta , Mila-Kierzenkowska Celestyna , Boraczyński Tomasz , Boraczyński Michał , Szewczyk-Golec Karolina , Sutkowy Paweł , Wesołowski Roland , Smoguła Małgorzata , Woźniak Alina
Published: September 2021

Cold-water immersion (CWI) after exercise is a method used by sportsmen to improve recovery. The aim of the study was to assess the effect of a 3 min CWI on the inflammatory state by measuring levels of interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α (TNF-α), and transforming growth factor β1 (TGF-β1), and activities of α1-antitrypsin (AAT) and lysosomal enzymes, including arylsulfatase (ASA), acid phosphatase (AcP), and cathepsin D (CTS D), in the blood of healthy recreational athletes. Male volunteers (n = 22, age 25 ± 4.8 yr) performed a 30 min submaximal aerobic exercise, followed by a 20 min rest at room temperature (RT-REST) or a 20 min rest at room temperature with an initial 3 min 8 °C water bath (CWI-REST). Blood samples were taken at baseline, immediately after exercise, and after 20 min of recovery. The IL-6, IL-10, and TNF-α levels and the AAT activity increased significantly immediately after exercise. The IL-6 level was significantly higher after CWI-REST than after RT-REST. No changes in the activities of the lysosomal enzymes were observed. The effect of a 3 min CWI on the level of inflammatory markers during post-exercise recovery was limited. Thus, it might be considered as a widely available method of regeneration for recreational athletes.
Running after Activated Clotting Time Values in Patients Receiving Direct Oral Anticoagulants: A Potentially Dangerous Race. Results from a Prospective Study in Atrial Fibrillation Catheter Ablation Procedures
Authors: Benali Karim , Verain Julien , Hammache Nefissa , Guenancia Charles , Hooks Darren , Magnin-Poull Isabelle , Toussaint-Hacquard Marie , de Chillou Christian , Sellal Jean-Marc
Published: September 2021

Background: Activated Clotting Time (ACT) guided heparinization is the gold standard for titrating unfractionated heparin (UFH) administration during atrial fibrillation (AF) ablation procedures. The current ACT target (300 s) is based on studies in patients receiving a vitamin K antagonist (VKA). Several studies have shown that in patients receiving Direct Oral Anticoagulants (DOACs), the correlation between ACT values and UFH delivered dose is weak. Objective: To assess the relationship between ACT and real heparin anticoagulant effect measured by anti-Xa activity in patients receiving different anticoagulant treatments. Methods: Patients referred for AF catheter ablation in our centre were prospectively included depending on their anticoagulant type. Results: 113 patients were included, receiving rivaroxaban (n = 30), apixaban (n = 30), dabigatran (n = 30), and VKA (n = 23). To meet target ACT, a higher UFH dose was required in DOAC than VKA patients (14,077.8 IU vs. 9565.2 IU, p < 0.001), leading to a longer time to achieve target ACT (46.5 min vs. 27.3 min, p = 0.001). The correlation of ACT and anti-Xa activity was tighter in the VKA group (Spearman correlation ρ = 0.53), compared to the DOAC group (ρ = 0.19). Despite lower ACT values in the DOAC group, this group demonstrated a higher mean anti-Xa activity compared to the VKA group (1.56 ± 0.39 vs. 1.14 ± 0.36; p = 0.002). Conclusion: Use of a conventional ACT threshold at 300 s during AF ablation procedures leads to a significant increase in UFH administration in patients treated with DOACs. This increase corresponds more likely to an overdosing than a real increase in UFH requirement.
The 5HTOL/5HIAA Ratio as a Biomarker of Alcohol Hangover
Authors: Mackus Marlou , van de Loo Aurora J. A. E. , van den Bogaard Willie J. M. , Korte-Bouws Gerdien A. H. , Garssen Johan , Verster Joris C.
Published: September 2021

Assessment of the presence and severity of alcohol hangovers relies on the subjective method of self-report. Therefore, there is a need of adequate biomarkers that (1) correlate significantly with hangover severity, and (2) correspond to the level of hangover-related performance impairment objectively. In this naturalistic study, n = 35 social drinkers participated. Urine samples were obtained the morning after alcohol consumption and after an alcohol-free control day. Concentrations of 5-hydroxytryptophol (5-HTOL), 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HTOL/5-HIAA ratio were determined. The results confirm previous findings that 5-HTOL and the 5HTOL/5-HIAA ratio are useful biomarkers of recent alcohol consumption. Significant correlations were found with the amount of alcohol consumed, total drink time, and estimated BAC. However, urine concentrations of 5-HTOL and 5-HIAA (and their ratio 5HTOL/5-HIAA) did not significantly correlate with hangover severity. In conclusion, urine 5-HTOL, 5-HIAA, and the 5HTOL/5-HIAA ratio cannot be considered to be suitable biomarkers of alcohol hangover.
Rapid Response System Improves Sepsis Bundle Compliances and Survival in Hospital Wards for 10 Years
Authors: Choi Sunhui , Son Jeongsuk , Oh Dong Kyu , Huh Jin Won , Lim Chae-Man , Hong Sang-Bum
Published: September 2021

Background: Hospitalized patients can develop septic shock at any time. Therefore, it is important to identify septic patients in hospital wards and rapidly perform the optimal treatment. Although the sepsis bundle has already been reported to improve survival rates, the controversy over evidence of the effect of in-hospital sepsis continues to exist. We aimed to estimate the outcomes and bundle compliance of patients with septic shock in hospital wards managed through the rapid response system (RRS). Methods: A retrospective cohort study of 976 patients with septic shock managed through the RRS at an academic, tertiary care hospital in Korea from 2008 to 2017. Results: Of the 976 enrolled patients, the compliance of each sepsis bundle was high (80.8–100.0%), but the overall success rate of the bundle was low (58.3%). The compliance rate for achieving the overall sepsis bundle increased from 26.5% to 70.0%, and the 28-day mortality continuously decreased from 50% to 32.1% over 10 years. We analyzed the two groups according to whether they completed the overall sepsis bundle or not. Of the 976 enrolled patients, 569 (58.3%) sepsis bundles were completed, whereas 407 (41.7%) were incomplete. The complete bundle group showed lower 28-day mortality than the incomplete bundle group (37.1% vs. 53.6%, p < 0.001). In the multivariate multiple logistic regression model, the 28-day mortality was significantly associated with the complete bundle (adjusted odds ratio (OR), 0.61; 95% confidence intervals (CI), 0.40–0.91; p = 0.017). The obtaining of blood cultures (adjusted OR, 0.45; 95% CI, 0.33–0.63; p < 0.001) and lactate re-measurement (adjusted OR, 0.69; 95% CI, 0.50–0.95; p = 0.024) in each component of the sepsis bundle were associated with the 28-day mortality. Conclusions: The rapid response system provides improving sepsis bundle compliances and survival in patients with septic shock in hospital wards.
Machine-Learning Points at Endoscopic, Quality of Life, and Olfactory Parameters as Outcome Criteria for Endoscopic Paranasal Sinus Surgery in Chronic Rhinosinusitis
Authors: Lötsch Jörn , Hintschich Constantin A. , Petridis Petros , Pade Jürgen , Hummel Thomas
Published: September 2021

Chronic rhinosinusitis (CRS) is often treated by functional endoscopic paranasal sinus surgery, which improves endoscopic parameters and quality of life, while olfactory function was suggested as a further criterion of treatment success. In a prospective cohort study, 37 parameters from four categories were recorded from 60 men and 98 women before and four months after endoscopic sinus surgery, including endoscopic measures of nasal anatomy/pathology, assessments of olfactory function, quality of life, and socio-demographic or concomitant conditions. Parameters containing relevant information about changes associated with surgery were examined using unsupervised and supervised methods, including machine-learning techniques for feature selection. The analyzed cohort included 52 men and 38 women. Changes in the endoscopic Lildholdt score allowed separation of baseline from postoperative data with a cross-validated accuracy of 85%. Further relevant information included primary nasal symptoms from SNOT-20 assessments, and self-assessments of olfactory function. Overall improvement in these relevant parameters was observed in 95% of patients. A ranked list of criteria was developed as a proposal to assess the outcome of functional endoscopic sinus surgery in CRS patients with nasal polyposis. Three different facets were captured, including the Lildholdt score as an endoscopic measure and, in addition, disease-specific quality of life and subjectively perceived olfactory function.
The Role of Neuropeptides in Pathogenesis of Dry Eye
Authors: Hwang Daniel , Lee Seok-Jae , Kim Jeong-Hun , Lee Sang-Mok
Published: September 2021

Neuropeptides are known as important mediators between the nervous and immune systems. Recently, the role of the corneal nerve in the pathogenesis of various ocular surface diseases, including dry eye disease, has been highlighted. Neuropeptides are thought to be important factors in the pathogenesis of dry eye disease, as suggested by the well-known role between the nervous and immune systems, and several recently published studies have elucidated the previously unknown pathogenic mechanisms involved in the role of the neuropeptides secreted from the corneal nerves in dry eye disease. Here, we reviewed the emerging concept of neurogenic inflammation as one of the pathogenic mechanisms of dry eye disease, the recent results of related studies, and the direction of future research.
Wide-Field Swept-Source OCT Analysis of Interocular Symmetry of Choroidal Thickness in Subjects with Uncomplicated Pachychoroid
Authors: Kim Min-Su , Lim Hyung-Bin , Lee Woo-Hyuk , Won Yeo-Kyoung , Nam Ki-Yup , Kim Jung-Yeul
Published: September 2021

Background: We aimed to study the bilateral choroidal thickness (CT) symmetry and difference in uncomplicated pachychoroid subjects using wide-field swept-source optical coherence tomography (SS-OCT). Methods: All subjects underwent a wide-field 16-mm one-line scan using SS-OCT. Bilateral CT was measured at, and compared among, the following 12 points: three points at 900-µm intervals from the nasal optic disc margin (nasal peripapillary area), one point at the subfovea, six points at 900-µm intervals from the fovea to the nasal and temporal areas (macular area), and two peripheral points 5400 and 8100 µm from the fovea (peripheral area). Results: There were no statistically significant differences in CT between the right and left eyes in any area (all p > 0.05); they all showed significant positive correlations (all p < 0.01). However, the correlation coefficients (ρ) were smaller for the nasal peripapillary and peripheral areas compared to the macular area. Conclusions: The CTs in each region were bilaterally symmetrical in subjects with uncomplicated pachychoroid. However, interocular difference in CT increased from the center to the periphery, indicating that the anatomical variation of the nasal peripapillary and peripheral choroid was greater than that of the macula.
Urinary Levels of Cathepsin B in Preterm Newborns
Authors: Kamianowska Monika , Szczepański Marek , Krukowska Anna , Kamianowska Aleksandra , Wasilewska Anna
Published: September 2021

Increased investment in perinatal health in developing countries has improved the survival of preterm newborns, but their significant multiorgan immaturity is associated with short and long-term adverse consequences. Cathepsin B, as a protease with angiogenic properties, may be related to the process of nephrogenesis. A total of 88 neonates (60 premature children, 28 healthy term children) were included in this prospective study. We collected urine samples on the first or second day of life. In order to determine the concentration of cathepsin B in the urine, the commercially available enzyme immunoassay was used. The urinary concentrations of cathepsin B normalized with the urinary concentrations of creatinine (cathepsin B/Cr.) in newborns born at 30–34, 35–36, and 37–41 (the control group) weeks of pregnancy were (median, Q1–Q3) 4.00 (2.82–5.12), 3.07 (1.95–3.90), and 2.51 (2.00–3.48) ng/mg Cr, respectively. Statistically significant differences were found between the group of newborns born at 30–34 weeks of pregnancy and the control group (p < 0.01), and between early and late preterm babies (PTB) (p < 0.05). The group of children born at 35–36 weeks of pregnancy and the control group did not differ significantly. This result suggests that the elevated urinary cathepsin B/Cr. level may be the result of the kidneys’ immaturity in preterm newborns.
Systemic Minoxidil Accidental Exposure in a Paediatric Population: A Case Series Study of Cutaneous and Systemic Side Effects
Authors: Sánchez-Díaz Manuel , López-Delgado David , Montero-Vílchez Trinidad , Salvador-Rodríguez Luis , Molina-Leyva Alejandro , Tercedor-Sánchez Jesús , Arias-Santiago Salvador
Published: September 2021

Oral minoxidil is an approved treatment for high blood pressure which is also used as an off-label drug for alopecia. Knowledge about the effects of systemic minoxidil in the paediatric population is limited. A retrospective case series study of paediatric patients with history of systemic minoxidil intake due to contaminated sets of omeprazole was performed to describe side effects of high dose oral minoxidil intake in children. Twenty patients aged between 2 months and 13 years joined the study. They had received high doses of oral minoxidil (mean dose 0.90 mg/kg/day) during a mean time of 38.3 days. Hypertrichosis appeared in 65%, with a mean latency time of 24.31 days. Treatment time was associated with the appearance of hypertrichosis (p < 0.05). Most common initial zone of hypertrichosis was the face. Systemic effects developed in 15%, with no cases of severe disorders. The present study shows a novel insight into the side effects of high doses of oral minoxidil in children.
Trends in the Incidence and Survival Rates of Colorectal Signet-Ring Cell Carcinoma in the South Korean Population: Analysis of the Korea Central Cancer Registry Database
Authors: Kim Ji-Hoon , Kim Hyunil , Kim Jin Woo , Kim Hee Man
Published: September 2021

Objective: Signet-ring cell carcinoma (SRCC) is a rare histopathological subtype of colorectal cancer (CRC) constituting approximately 1% of CRC cases. This study analyzed the incidence and survival rates of colorectal SRCC. Methods: We analyzed the incidence and survival rates of colorectal SRCCs based on patients’ data of the Korea Central Cancer Registry. Results: The age-standardized incidence rates of colon and rectum SRCC in 2017 were 0.17 and 0.07 individuals per 100,000, respectively. Between 1993 and 2017, the 1-, 2-, 3-, 4-, and 5-year relative survival rates of patients with colon SRCC were 65.6%, 49.0%, 38.9%, 34.9%, and 33.0%, respectively, while those of patients with rectum SRCC were 69.6%, 47.8%, 38.5%, 32.8%, and 29.4%, respectively. According to the Surveillance, Epidemiology, and End Results summary stages, the 5-year relative survival rates of colon SRCC between 1993 and 2017 were 70.4% for the localized stage, 41.0% for the regional stage, and 7.0% for the distant stage, while those for rectum SRCC were 60.7%, 34.4, and 3.3%, respectively. Conclusions: Although the incidence of colorectal SRCC is extremely low in South Korea, it has been increasing in recent decades. As the prognosis of colorectal SRCC is extremely poor; clinicians should be aware of the differential diagnosis of SRCC in colorectal cancer cases.
Early Improvements in Disease Activity Indices Predict Long-Term Clinical Remission Suggested by the Treat-to-Target Strategy in Patients with Ankylosing Spondylitis Receiving TNF-α Inhibitor Treatment
Authors: Nam Eon Jeong , Lee Won Kee
Published: September 2021

This study evaluated the possibility of clinical remission suggested by the treat-to-target strategy and identified predictors of clinical remission in 139 patients with ankylosing spondylitis (AS) receiving tumor necrosis factor-α inhibitors (TNFi). Clinical remission criteria selected were AS Disease Activity Score Inactive Disease (ASDAS-ID) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 2 with normal C-reactive protein (CRP) levels (BASDAI-CRP). The longitudinal relationship between clinical parameters and clinical remission was assessed using generalized estimating equations (GEEs). Responders to ASDAS-ID and BASDAI-CRP increased from 32.4% to 68.9% and from 39.9% to 75.2% at months 3 and 33, respectively. Responders to ASDAS-ID and BASDAI-CRP almost overlapped. In the univariable GEE model, age and 3-month improvement in BASDAI, ASDAS-CRP, physician and patient global assessments, and spinal pain predicted clinical remission achievement, while the presence of syndesmophytes predicted ASDAS-CRP achievement, and normalized CRP at 3 months was associated with BASDAI-CRP achievement. Multivariable GEE analysis revealed age (odds ratio (OR): 0.67; 95% confidence interval (CI), 0.49–0.93) and 3-month BASDAI improvement (OR: 1.70; CI, 1.19–2.41) as independent predictors of ASDAS-ID achievement and age (OR: 0.69; CI, 0.54–0.89), 3-month BASDAI improvement (OR: 2.00; CI, 1.45–2.76), and normalized CRP at 3 months (OR: 3.72; CI, 1.39–9.95) as independent predictors of BASDAI-CRP achievement.
Electrical and Mechanical Properties of Sugarcane Bagasse Pyrolyzed Biochar Reinforced Polyvinyl Alcohol Biocomposite Films
Authors: Ahmed Kawsar , Hasan Mahbub , Haider Julfikar
Published: September 2021

Biochar obtained from the oxygen-deficient thermochemical processing of organic wastes is considered to be an effective reinforcing agent in biocomposite development. In the present research, biocomposite film was prepared using sugarcane bagasse pyrolyzed biochar and polyvinyl alcohol (PVA), and its electrical and mechanical properties were assessed. The biocomposite films were produced by varying content (5 wt.%, 8 wt.% and 12 wt.%) of the biochar produced at 400 °C, 600 °C, 800 °C and 1000 °C and characterized using X-Ray diffraction, scanning electron microscope, Fourier transform infrared spectroscopy. The experimental findings revealed that biochar produced at a higher pyrolyzing temperature could significantly improve the electrical conductance of the biocomposite film. A maximum electrical conductance of 7.67 × 10−2 S was observed for 12 wt.% addition of biochar produced at 1000 °C. A trend of improvement in the electrical properties of the biocomposite films suggested a threshold wt.% of the biochar needed to make a continuous conductive network across the biocomposite film. Rapid degradation of tensile strength was observed with an increasing level of biochar dosage. The lowest tensile strength 3.12 MPa was recorded for the film with 12 wt.% of biochar produced at 800 °C. Pyrolyzing temperature showed a minor impact on the mechanical strength of the biocomposite. The prepared biocomposites could be used as an electrically conductive layer in electronic devices.
Benzoxazine Copolymers with Mono- and Difunctional Epoxy Active Diluents with Enhanced Tackiness and Reduced Viscosity
Authors: Bornosuz Natalia V. , Korotkov Roman F. , Shutov Vyacheslav V. , Sirotin Igor S. , Gorbunova Irina Yu.
Published: September 2021

The influence of epoxy active diluents, 1,4-butanediol diglycidyl ether (BD) and furfuryl glycidyl ether (FUR), in the mixtures with benzoxazine monomer based on bisphenol A, formaldehyde and m-toluidine (BA-mt), on the properties of a matrix was disclosed in this work. Resins were modified to achieve good tackiness at room temperature and reduced viscosity. The influence of mono- and difunctional modifiers on the process of curing was studied by way of differential scanning calorimetry and oscillatory rheology. The addition of BD and FUR shifted the curing peak to higher temperatures and significantly reduced viscosity. Preferable tackiness at ambient temperature was achieved with 10 phr of epoxy components in mixtures. However, cured blends with difunctional epoxy BD had an advantage over monofunctional FUR in enhanced tensile strength with remaining glass transition temperature at the level of neat benzoxazine (217 °C).