bluuebunny/crossref_metadata_2025 huggingface dataset:
The Memory of Rice Response to Spaceflight Stress: From the Perspective of Metabolomics and Proteomics
Authors: Zeng Deyong , Cui Jie , Yin Yishu , Xiong Yi , Yu Wenchen , Zhao Haitian , Guan Shuanghong , Cheng Dayou , Sun Yeqing , Lu Weihong
Published: March 2022

The stress response of plants to spaceflight has been confirmed in contemporary plants, and plants retained the memory of spaceflight through methylation reaction. However, how the progeny plants adapt to this cross-generational stress memory was rarely reported. Here, we used the ShiJian-10 retractable satellite carrying Dongnong416 rice seeds for a 12.5-day on-orbit flight and planted the F2 generation after returning to the ground. We evaluated the agronomic traits of the F2 generation plants and found that the F2 generation plants had no significant differences in plant height and number of tillers. Next, the redox state in F2 plants was evaluated, and it was found that the spaceflight broke the redox state of the F2 generation rice. In order to further illustrate the stress response caused by this redox state imbalance, we conducted proteomics and metabolomics analysis. Proteomics results showed that the redox process in F2 rice interacts with signal transduction, stress response, and other pathways, causing genome instability in the plant, leading to transcription, post-transcriptional modification, protein synthesis, protein modification, and degradation processes were suppressed. The metabolomics results showed that the metabolism of the F2 generation plants was reshaped. These metabolic pathways mainly included amino acid metabolism, sugar metabolism, cofactor and vitamin metabolism, purine metabolism, phenylpropane biosynthesis, and flavonoid metabolism. These metabolic pathways constituted a new metabolic network. This study confirmed that spaceflight affected the metabolic changes in offspring rice, which would help better understand the adaptation mechanism of plants to the space environment.
Improvements, Variations and Biomedical Applications of the Michaelis–Arbuzov Reaction
Authors: Kostoudi Stavroula , Pampalakis Georgios
Published: March 2022

Compounds bearing the phosphorus–carbon (P–C) bond have important pharmacological, biochemical, and toxicological properties. Historically, the most notable reaction for the formation of the P–C bond is the Michaelis–Arbuzov reaction, first described in 1898. The classical Michaelis–Arbuzov reaction entails a reaction between an alkyl halide and a trialkyl phosphite to yield a dialkylalkylphosphonate. Nonetheless, deviations from the classical mechanisms and new modifications have appeared that allowed the expansion of the library of reactants and consequently the chemical space of the yielded products. These involve the use of Lewis acid catalysts, green methods, ultrasound, microwave, photochemically-assisted reactions, aryne-based reactions, etc. Here, a detailed presentation of the Michaelis–Arbuzov reaction and its developments and applications in the synthesis of biomedically important agents is provided. Certain examples of such applications include the development of alkylphosphonofluoridates as serine hydrolase inhibitors and activity-based probes, and the P–C containing antiviral and anticancer agents.
Shikonin Derivatives Inhibit Inflammation Processes and Modulate MAPK Signaling in Human Healthy and Osteoarthritis Chondrocytes
Authors: Lohberger Birgit , Kaltenegger Heike , Eck Nicole , Glänzer Dietmar , Sadoghi Patrick , Leithner Andreas , Bauer Rudolf , Kretschmer Nadine , Steinecker-Frohnwieser Bibiane
Published: March 2022

Osteoarthritis (OA) is the most common joint disorder and is characterized by the degeneration of articular cartilage. To develop new therapeutic approaches, we investigated the effect of shikonin derivatives on inflammation, MMP expression, and the regulation of MAPK signaling in human healthy (HC) and OA chondrocytes (pCH-OA). Viability was analyzed using the CellTiter-Glo® Assay. Inflammatory processes were investigated using a proteome profiler™ assay. Furthermore, we analyzed the effects of the shikonin derivatives by protein expression analysis of the phosphorylation pattern and the corresponding downstream gene regulation using RT-qPCR. Both HC and pCH-OA showed a dose-dependent decrease in viability after treatment. The strongest effects were found for shikonin with IC50 values of 1.2 ± 0.1 µM. Shikonin counteracts the inflammatory response by massively reducing the expression of the pro-inflammatory mediators. The phosphorylation level of ERK changed slightly. pJNK and pp38 showed a significant increase, and the downstream targets c/EBPs and MEF2c may play a role in the cartilage homeostasis. STAT3 phosphorylation decreased significantly and has a chondroprotective function through the regulation of cyclin D1 and Sox9. Our results demonstrate for the first time that shikonin derivatives have extensive effects on the inflammatory processes, MAPKs, and IL6/STAT3 downstream regulation in healthy and OA chondrocytes.
Susceptibility of Female Mice to the Dietary Omega-3/Omega-6 Fatty-Acid Ratio: Effects on Adult Hippocampal Neurogenesis and Glia
Authors: Rodríguez-Iglesias Noelia , Nadjar Agnes , Sierra Amanda , Valero Jorge
Published: March 2022

Maternal intake of omega-3 (n-3 PUFAs) and omega-6 (n-6 PUFAs) polyunsaturated fatty acids impacts hippocampal neurogenesis during development, an effect that may extend to adulthood by altering adult hippocampal neurogenesis (AHN). The n-3 PUFAs and n-6 PUFAs are precursors of inflammatory regulators that potentially affect AHN and glia. Additionally, n-3 PUFA dietary supplementation may present a sexually dimorphic action in the brain. Therefore, we postulated that dietary n-6/n-3 PUFA balance shapes the adult DG in a sex-dependent manner influencing AHN and glia. We test our hypothesis by feeding adult female and male mice with n-3 PUFA balanced or deficient diets. To analyze the immunomodulatory potential of the diets, we injected mice with the bacterial endotoxin lipopolysaccharide (LPS). LPS reduced neuroblast number, and its effect was exacerbated by the n-3 PUFA-deficient diet. The n-3 PUFA-deficient diet reduced the DG volume, AHN, microglia number, and surveilled volume. The diet effect on most mature neuroblasts was exclusively significant in female mice. Colocalization and multivariate analysis revealed an association between microglia and AHN, as well as the sexual dimorphic effect of diet. Our study reveals that female mice are more susceptible than males to the effect of dietary n-6/n-3 PUFA ratio on AHN and microglia.
Treatment of Critical Size Femoral Bone Defects with Biomimetic Hybrid Scaffolds of 3D Plotted Calcium Phosphate Cement and Mineralized Collagen Matrix
Authors: Culla Anna Carla , Vater Corina , Tian Xinggui , Bolte Julia , Ahlfeld Tilman , Bretschneider Henriette , Pape Alexander , Goodman Stuart B. , Gelinsky Michael , Zwingenberger Stefan
Published: March 2022

To treat critical-size bone defects, composite materials and tissue-engineered bone grafts play important roles in bone repair materials. The purpose of this study was to investigate the bone regenerative potential of hybrid scaffolds consisting of macroporous calcium phosphate cement (CPC) and microporous mineralized collagen matrix (MCM). Hybrid scaffolds were synthetized by 3D plotting CPC and then filling with MCM (MCM-CPC group) and implanted into a 5 mm critical size femoral defect in rats. Defects left empty (control group) as well as defects treated with scaffolds made of CPC only (CPC group) and MCM only (MCM group) served as controls. Eight weeks after surgery, micro-computed tomography scans and histological analysis were performed to analyze the newly formed bone, the degree of defect healing and the activity of osteoclasts. Mechanical stability was tested by 3-point-bending of the explanted femora. Compared with the other groups, more newly formed bone was found within MCM-CPC scaffolds. The new bone tissue had a clamp-like structure which was fully connected to the hybrid scaffolds and thereby enhanced the biomechanical strength. Together, the biomimetic hybrid MCM-CPC scaffolds enhanced bone defect healing by improved osseointegration and their differentiated degradation provides spatial effects in the process of critical-bone defect healing.
Dynamics of Plasma and Urinary Extracellular DNA in Acute Kidney Injury
Authors: Jančuška Alexander , Potočárová Alena , Kovalčíková Alexandra Gaál , Podracká Ľudmila , Bábíčková Janka , Celec Peter , Tóthová Ľubomíra
Published: March 2022

Early and reliable markers of acute kidney injury (AKI) are essential. One such candidate marker of tissue damage is extracellular DNA (ecDNA). The aim of our present study is to describe the unknown dynamics of ecDNA in an animal model of AKI. Glycerol-induced nephropathy was used to model AKI in adult male Wistar rats (n = 93). Blood and urine samples were collected 1, 3, and 24 h after model induction. Total ecDNA and its sub-cellular origin was assessed. In the plasma, total ecDNA and nuclear ecDNA were significantly increased in the AKI group already after 1 h (160% and 270%, respectively, p = 0.02 and p = 0.04). Both nuclear and mitochondrial ecDNA were higher after 3 h (180% and 170%, respectively, p = 0.002 and p = 0.005). Urinary ecDNA concentrations in the AKI group were significantly increased only 24 h after model induction (130% for total ecDNA, p = 0.009; 210% for nuclear ecDNA, p = 0.02; and 200% for mitochondrial ecDNA, p = 0.0009). Our results indicate that plasma ecDNA has the potential to serve as an early and sensitive, albeit non-specific marker of AKI. Further studies should elucidate the source of ecDNA and the dynamics of ecDNA in other animal models of AKI and patients with AKI.
Mechanisms and Applications of Bacterial Sporulation and Germination in the Intestine
Authors: Koopman Nienke , Remijas Lauren , Seppen Jurgen , Setlow Peter , Brul Stanley
Published: March 2022

Recent studies have suggested a major role for endospore forming bacteria within the gut microbiota, not only as pathogens but also as commensal and beneficial members contributing to gut homeostasis. In this review the sporulation processes, spore properties, and germination processes will be explained within the scope of the human gut. Within the gut, spore-forming bacteria are known to interact with the host’s immune system, both in vegetative cell and spore form. Together with the resistant nature of the spore, these characteristics offer potential for spores’ use as delivery vehicles for therapeutics. In the last part of the review, the therapeutic potential of spores as probiotics, vaccine vehicles, and drug delivery systems will be discussed.
Formate Dehydrogenase Improves the Resistance to Formic Acid and Acetic Acid Simultaneously in Saccharomyces cerevisiae
Authors: Du Cong , Li Yimin , Xiang Ruijuan , Yuan Wenjie
Published: March 2022

Bioethanol from lignocellulosic biomass is a promising and sustainable strategy to meet the energy demand and to be carbon neutral. Nevertheless, the damage of lignocellulose-derived inhibitors to microorganisms is still the main bottleneck. Developing robust strains is critical for lignocellulosic ethanol production. An evolved strain with a stronger tolerance to formate and acetate was obtained after adaptive laboratory evolution (ALE) in the formate. Transcriptional analysis was conducted to reveal the possible resistance mechanisms to weak acids, and fdh coding for formate dehydrogenase was selected as the target to verify whether it was related to resistance enhancement in Saccharomyces cerevisiae F3. Engineered S. cerevisiae FA with fdh overexpression exhibited boosted tolerance to both formate and acetate, but the resistance mechanism to formate and acetate was different. When formate exists, it breaks down by formate dehydrogenase into carbon dioxide (CO2) to relieve its inhibition. When there was acetate without formate, FDH1 converted CO2 from glucose fermentation to formate and ATP and enhanced cell viability. Together, fdh overexpression alone can improve the tolerance to both formate and acetate with a higher cell viability and ATP, which provides a novel strategy for robustness strain construction to produce lignocellulosic ethanol.
Syndecan-3 as a Novel Biomarker in Alzheimer’s Disease
Authors: Hudák Anett , Letoha Annamária , Vizler Csaba , Letoha Tamás
Published: March 2022

Early diagnosis of Alzheimer’s disease (AD) is of paramount importance in preserving the patient’s mental and physical health in a fairly manageable condition for a longer period. Reliable AD detection requires novel biomarkers indicating central nervous system (CNS) degeneration in the periphery. Members of the syndecan family of transmembrane proteoglycans are emerging new targets in inflammatory and neurodegenerative disorders. Reviewing the growing scientific evidence on the involvement of syndecans in the pathomechanism of AD, we analyzed the expression of the neuronal syndecan, syndecan-3 (SDC3), in experimental models of neurodegeneration. Initial in vitro studies showed that prolonged treatment of tumor necrosis factor-alpha (TNF-α) increases SDC3 expression in model neuronal and brain microvascular endothelial cell lines. In vivo studies revealed elevated concentrations of TNF-α in the blood and brain of APPSWE-Tau transgenic mice, along with increased SDC3 concentration in the brain and the liver. Primary brain endothelial cells and peripheral blood monocytes isolated from APPSWE-Tau mice exhibited increased SDC3 expression than wild-type controls. SDC3 expression of blood-derived monocytes showed a positive correlation with amyloid plaque load in the brain, demonstrating that SDC3 on monocytes is a good indicator of amyloid pathology in the brain. Given the well-established role of blood tests, the SDC3 expression of monocytes could serve as a novel biomarker for early AD detection.
Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome
Authors: Parente Martina , Tonini Claudia , Buzzelli Valeria , Carbone Emilia , Trezza Viviana , Pallottini Valentina
Published: March 2022

Fragile X Syndrome (FXS) is the most frequent form of inherited X-linked pathology, associated with an intellectual and developmental disability, and currently considered the first monogenic cause of autism spectrum disorder (ASD). Low levels of total cholesterol reported in the serum of FXS patients, and evidence that FMRP targets a subset of mRNAs encoding proteins of lipid synthesis and transport suggests that the cholesterol metabolism impairments could be involved in FXS. Thus, the aim of the presented work was to investigate the modulations of the cholesterol biosynthetic pathway and its end-products in a recently developed Fmr1-Δexon 8 rat model of FXS. Here, we show that this experimental model mimics what is found in FXS patients, exhibiting a lower serum cholesterol content, accompanied by a reduction in food intake and body weight compared to WT animals. Moreover, alterations of proteins committed to cholesterol synthesis and uptake have been observed in the amygdala, prefrontal cortex and nucleus accumbens. Interestingly, the end-products show a brain region-dependent modulation in Fmr1-Δexon 8 rats. Overall, our results demonstrate that the cholesterol biosynthetic pathway is altered in some brain regions of this preclinical model of FXS. This finding has relevance for future studies to delve deeper into the involvement of this metabolic process in FXS, and thus its possible role as a therapeutic target.
Nucleobase-Derived Nitrones: Synthesis and Antioxidant and Neuroprotective Activities in an In Vitro Model of Ischemia–Reperfusion
Authors: Chamorro Beatriz , Głowacka Iwona E. , Gotkowska Joanna , Gulej Rafał , Hadjipavlou-Litina Dimitra , López-Muñoz Francisco , Marco-Contelles José , Piotrowska Dorota G. , Oset-Gasque María Jesús
Published: March 2022

Herein, we report the synthesis, antioxidant, and neuroprotective properties of some nucleobase-derived nitrones named 9a–i. The neuroprotective properties of nitrones, 9a–i, were measured against an oxygen-glucose-deprivation in vitro ischemia model using human neuroblastoma SH-SY5Y cells. Our results indicate that nitrones, 9a–i, have better neuroprotective and antioxidant properties than α-phenyl-N-tert-butylnitrone (PBN) and are similar to N-acetyl-L-cysteine (NAC), a well-known antioxidant and neuroprotective agent. The nitrones with the highest neuroprotective capacity were those containing purine nucleobases (nitrones 9f, g, B = adenine, theophylline), followed by nitrones with pyrimidine nucleobases with H or F substituents at the C5 position (nitrones 9a, c). All of these possess EC50 values in the range of 1–6 μM and maximal activities higher than 100%. However, the introduction of a methyl substituent (nitrone 9b, B = thymine) or hard halogen substituents such as Br and Cl (nitrones 9d, e, B = 5-Br and 5-Cl uracil, respectively) worsens the neuroprotective activity of the nitrone with uracil as the nucleobase (9a). The effects on overall metabolic cell capacity were confirmed by results on the high anti-necrotic (EC50′s ≈ 2–4 μM) and antioxidant (EC50′s ≈ 0.4–3.5 μM) activities of these compounds on superoxide radical production. In general, all tested nitrones were excellent inhibitors of superoxide radical production in cultured neuroblastoma cells, as well as potent hydroxyl radical scavengers that inhibit in vitro lipid peroxidation, particularly, 9c, f, g, presenting the highest lipoxygenase inhibitory activity among the tested nitrones. Finally, the introduction of two nitrone groups at 9a and 9d (bis-nitronas 9g, i) did not show better neuroprotective effects than their precursor mono-nitrones. These results led us to propose nitrones containing purine (9f, g) and pyrimidine (9a, c) nucleobases as potential therapeutic agents for the treatment of cerebral ischemia and/or neurodegenerative diseases, leading us to further investigate their effects using in vivo models of these pathologies.
Factors Affecting Reputational Damage to Organisations Due to Cyberattacks
Authors: Perera Srinath , Jin Xiaohua , Maurushat Alana , Opoku De-Graft Joe
Published: March 2022

The COVID-19 pandemic has brought massive online activities and increased cybersecurity incidents and cybercrime. As a result of this, the cyber reputation of organisations has also received increased scrutiny and global attention. Due to increased cybercrime, reputation displaying a more important role within risk management frameworks both within public and private institutions is vital. This study identifies key factors in determining reputational damage to public and private sector institutions through cyberattacks. Researchers conducted an extensive review of the literature, which addresses factors relating to risk management of reputation post-cyber breach. The study identified 42 potential factors, which were then classified using the STAR model. This model is an organisational design framework and was suitable due to its alignment with organisations. A qualitative study using semi-structured and structured questions was conducted with purposively selected cybersecurity experts in both public and private sector institutions. Data obtained from the expert forum were analysed using thematic analysis, which revealed that a commonly accepted definition for cyber reputation was lacking despite the growing use of the term “online reputation”. In addition, the structured questions data were analysed using relative importance index rankings. The analysis results revealed significant factors in determining reputational damage due to cyberattacks, as well as highlighting reputation factor discrepancies between private and public institutions. Theoretically, this study contributes to the body of knowledge relating to cybersecurity of organisations. Practically, this research is expected to aid organisations to properly position themselves to meet cyber incidents and become more competitive in the post-COVID-19 era.
Improved Electrochemical Behavior and Thermal Stability of Li and Mn-Rich Cathode Materials Modified by Lithium Sulfate Surface Treatment
Authors: Sclar Hadar , Maiti Sandipan , Sharma Rosy , Erickson Evan M. , Grinblat Judith , Raman Ravikumar , Talianker Michael , Noked Malachi , Kondrakov Aleksandr , Markovsky Boris , Aurbach Doron
Published: March 2022

High-energy cathode materials that are Li- and Mn-rich lithiated oxides—for instance, 0.35Li2MnO3.0.65LiNi0.35Mn0.45Co0.20O2 (HE-NCM)—are promising for advanced lithium-ion batteries. However, HE-NCM cathodes suffer from severe degradation during cycling, causing gradual capacity loss, voltage fading, and low-rate capability performance. In this work, we applied an effective approach to creating a nano-sized surface layer of Li2SO4 on the above material, providing mitigation of the interfacial side reactions while retaining the structural integrity of the cathodes upon extended cycling. The Li2SO4 coating was formed on the surface of the material by mixing it with nanocrystalline Li2SO4 and annealing at 600 °C. We established enhanced electrochemical behavior with ~20% higher discharge capacity, improved charge-transfer kinetics, and higher rate capability of HE-NCM cathodes due to the presence of the Li2SO4 coating. Online electrochemical mass spectrometry studies revealed lower CO2 and H2 evolution in the treated samples, implying that the Li2SO4 layer partially suppresses the electrolyte degradation during the initial cycle. In addition, a ~28% improvement in the thermal stability of the Li2SO4-treated samples in reactions with battery solution was also shown by DSC studies. The post-cycling analysis allowed us to conclude that the Li2SO4 phase remained on the surface and retained its structure after 100 cycles.
Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 Plays an Important Role in the Development and Reproduction of Nilaparvata lugens
Authors: Ji Jin-Liang , Han Shan-Jie , Zhang Rui-Juan , Yu Jian-Bin , Li Ya-Bin , Yu Xiao-Ping , Liu Guang-Fu , Xu Yi-Peng
Published: March 2022

The brown planthopper, Nilaparvata lugens, is a difficult-to-control insect pest affecting rice yields in Asia. As a structural component of the inter-alpha-trypsin inhibitor (ITI), the inter-alpha-trypsin inhibitor heavy chain (ITIH) has been reported to be involved in various inflammatory or malignant disorders, ovarian development, and ovulation. To reveal the function of ITIH4 in N. lugens, the gene encoding N. lugens ITIH4 (NlITIH4) was cloned and characterized. NlITIH4 contains a signal peptide, a vault protein inter-alpha-trypsin domain, and a von Willebrand factor type A domain. qPCR analysis showed that NlITIH4 was expressed at all developmental stages and in all tissues (fat body, ovary, and gut), with the highest expression in the fat body. Double stranded NlITIH4 (dsNlITIH4) injection clearly led to an RNAi-mediated inhibition of the expression of NlITIH4 and resulted in reduced survival, delayed ovarian development, and reduced egg production and egg hatching. These results indicate that NlITIH4 plays an important role in the development and reproduction of N. lugens.
Establishment, Genetic Diversity, and Habitat Suitability of Aedes albopictus Populations from Ecuador
Authors: Carrazco-Montalvo Andrés , Ponce Patricio , Villota Stephany D. , Quentin Emmanuelle , Muñoz-Tobar Sofía , Coloma Josefina , Cevallos Varsovia
Published: March 2022

Aedes albopictus, also known as the tiger mosquito, is widespread worldwide across tropical, subtropical, and temperate regions. This insect is associated with the transmission of several vector-borne diseases, and, as such, monitoring its distribution is highly important for public health. In Ecuador, Ae. albopictus was first reported in 2017 in Guayaquil. Since then, the vector has been identified in the Northeastern lowlands and the Amazon basin. This study aims to determine the genetic diversity of Ecuadorian populations of Ae. albopictus through the analysis of the mitochondrial gene COI and to describe the potential distribution areas of this species within the country. The genetic diversity was determined by combining phylogenetic and population genetics analyses of five localities in Ecuador. Results showed two haplotypes in the Ecuadorian populations of Ae. albopictus. Haplotype 1 (H1) was found in the coastal and Amazon individuals, while haplotype 2 (H2) was only found in the three northeastern lowlands sites. In a worldwide context, H1 is the most widespread in 21 countries with temperate and tropical habitats. In contrast, H2 distribution is limited to five countries in tropical regions, suggesting fewer adaptation traits. Our prediction model showed a suitable habitat for Ae. albopictus in all regions (coastal, Amazon basin, and Andean lowland regions and the Galápagos Islands) of Ecuador. Hence, understanding different aspects of the vector can help us implement better control strategies for surveillance and vectorial control in Ecuador.
Oxidative and Antioxidative Status Expressed as OSI Index and GSH/GSSG Ratio in Children with Bone Tumors after Anticancer Therapy Completion
Authors: Gajewska Joanna , Chełchowska Magdalena , Rychłowska-Pruszyńska Magdalena , Klepacka Teresa , Ambroszkiewicz Jadwiga
Published: March 2022

Aims. There are no data on the redox status of children with bone tumors in complete disease remission. Therefore, the presented study examined the reduced/oxidized glutathione (GSH/GSSG) ratio, total oxidant capacity (TOC) and total antioxidant capacity (TAC) values as well as the oxidative stress index (OSI) for assessing alterations in the oxidant/antioxidant balance in 35 children with osteosarcoma or Ewing’s sarcoma after anticancer therapy completion (median 14 months) compared with a control group. Methods. GSH, GSSG, TOC, TAC concentrations and bone alkaline phosphatase (BALP) activity were evaluated by immunoenzymatic (ELISA) and enzymatic methods. Results. We found no differences in serum BALP activity between all survivors with bone tumors and the control group. Patients with osteosarcoma after anticancer therapy completion had significantly higher values of TAC, GSH and the GSH/GSSG ratio as well as GSSG than healthy subjects. In patients with Ewing’s sarcoma, we found significantly higher values of TOC concentration compared with healthy children. In addition, survivors with Ewing’s sarcoma had higher TOC concentrations and OSI index values (p < 0.01), but a lower GSH/GSSG ratio (p < 0.05) than survivors with osteosarcoma. A positive correlation between TOC and the post-therapy period was observed in survivors. Conclusions. We found that in survivors with bone tumors, a disturbed balance between prooxidants and antioxidants persists after the completion of anticancer treatment. Moreover, an increased TOC value together with the post-therapy period may suggest increasing oxidative processes in survivors with bone tumors after treatment. Further observations will allow assessment of the relationship between the oxidant/antioxidant status and the predisposition of survivors to bone neoplastic disease recurrence.
Mid- and Long-Term Results Using 448 kHz Stimulation on the Elasticity of the Supraspinatus Tendon Measured by Quantitative Ultrasound Elastographyin Badminton Professionals: Prospective Randomized Double-Blinded Clinical Trial with Nine Months of Follow-Up
Authors: Navarro-Ledesma Santiago , Gonzalez-Muñoz Ana
Published: March 2022

The aim of this study is to analyse the changes that occur in the elasticity of the supraspinatus tendon after the application of a 448 kHz capacitive resistive monopolar radiofrequency (CRMR) at 3, 6 and 9 months in professional badminton players. A randomized double-blinded clinical trial that included 9 months of follow-up was used. A private care practice was used to recruit the participants of this study. They were randomly assigned either the CRMR treatment (n = 19) or the placebo treatment (n = 19). The experimental group received a total of nine treatments of 448 kHz CRMR divided into three treatments per week. The control group received the same regimen but with no radiofrequency. Quantitative ultrasound strain elastography was used to report the main values for three areas of the supraspinatus tendon. These were measured at the start (T1) and directly after (T2), one week after, (T3), three months after (T4), six months after (T5) and nine months after (T6) the completion of the intervention program. There were statistically significant differences in the supraspinatus tendon elasticity immediately after (p ≤ 0.001), one week after (p ≤ 0.001) and three months after (p = 0.01) the intervention program. No significant changes were found six or nine months after the intervention program. A three-week intervention program using 448 kHz produced significant changes in the elasticity of the supraspinatus tendon, with the changes lasting up to approximately three months when compared to the control group.
Response Assessment to Erythropoietin-Zeta (Epo-Alpha Biosimilar) Therapy in Low-Risk Myelodysplastic Syndromes
Authors: Vetro Calogero , Di Giacomo Valeria , Mannina Donato , Magrin Silvana , Mulè Antonio , Mitra Maria Enza , Siragusa Sergio , Duminuco Andrea , Garibaldi Bruno , Vadalà Maria Cristina Emanuela , Di Raimondo Francesco , Palumbo Giuseppe A.
Published: March 2022

Background. This prospective observational study aimed to verify the efficacy of erythropoietin zeta in the treatment of patients with low-risk myelodysplastic syndrome. Methods. Patients with low/int-1 IPSS risk and serum erythropoietin level below 500 U/L were enrolled. Treatment consisted of erythropoietin zeta 40,000 U subcutaneously once a week. The primary endpoint was the erythroid response. According to Simon’s two-stage statistical design, 36 patients were recruited. The median age was 75 years (range 56–83 years), male/female ratio was 1.1/1, median baseline serum erythropoietin was 57.9 U/L (range 9.4–475 U/L). 53% of patients had low-risk disease, while the remaining had Int-1 risk. Results. After 8 weeks, a significant response (rise in Hb levels of at least 1.5 g/dL) was achieved in 18 patients (50%) out of 36. However, 17 patients did not improve; 8/17 patients pursued the 40,000 U weekly schedule of erythropoietin zeta, and 4/8 (50%) of them reached the erythroid response after 16 weeks. Nine patients underwent dosage doubling (40,000 U twice per week), and 5/9 (55%) of them achieved the erythroid response. Conclusion. Compared with data from the literature, this prospective study revealed that EPO-zeta is a safe and effective therapeutic option in low-risk MDS patients.
Does Additional Dietary Supplementation Improve Physiotherapeutic Treatment Outcome in Tendinopathy? A Systematic Review and Meta-Analysis
Authors: Qiu Fanji , Li Jinfeng , Legerlotz Kirsten
Published: March 2022

A systematic review and meta-analysis of randomized controlled trials was performed to evaluate the effects of dietary supplements in addition to physiotherapeutic treatment on pain and functional outcomes. PubMed, The Cochrane Library, Web of Science, and Embase were searched from inception to November 2021 (Prospero registration: CRD42021291951). Studies were eligible if the interventions consisted of physiotherapeutic approaches that were combined with dietary supplementation and if they reported measures of pain and/or function. Six studies were included in the meta-analysis. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated and analysed using a Review Manager software. Subgroup analysis was performed to explore possible associations between the study characteristics and the effectiveness of the intervention. Additional dietary supplementation during physiotherapeutic treatment significantly improved the reduction in pain score (SMD = −0.74, 95% CI, −1.37 to −0.10; p < 0.05), while it had no effect on functional outcomes (SMD = 0.29, 95% CI, 0.00 to 0.58; p > 0.05). This systematic review and meta-analysis suggests that additional nutritional interventions may improve physiotherapeutic treatment outcomes in the management of tendinopathies.
Correction: Kim et al. Diagnostic Value of Multiple Serum Biomarkers for Vancomycin-Induced Kidney Injury. J. Clin. Med. 2021, 10, 5005
Authors: Kim Sang-Mi , Lee Hyun-Seung , Kim Min-Ji , Park Hyung-Doo , Lee Soo-Youn
Published: March 2022

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Heparanase Inhibition Prevents Liver Steatosis in E0 Mice
Authors: Kinaneh Safa , Hijaze Walaa , Mansour-Wattad Lana , Hammoud Rawan , Zaidani Hisam , Kabala Aviva , Hamoud Shadi
Published: March 2022

Background: Non-alcoholic fatty liver disease affects up to 30% of adults in the USA, and is associated with a higher incidence of chronic liver morbidity and mortality. Several molecular pathways are involved in the pathology of liver steatosis, including lipid uptake, lipogenesis, lipolysis, and beta-oxidation. The enzyme heparanase has been implicated in liver steatosis. Herein, we investigated the effect of heparanase inhibition on liver steatosis in E0 mice. Methods: In vivo experiments: Male wild-type mice fed with either chow diet (n = 4) or high-fat diet (n = 6), and male E0 mice fed with chow diet (n = 8) or high-fat diet (n = 33) were included. Mice on a high-fat diet were treated for 12 weeks with PG545 at low dose (6.4 mg/kg/week, ip, n = 6) or high dose (13.3 mg/kg/week, ip, n = 7), SST0001 (1.2 mg/mouse/day, ip, n = 6), or normal saline (control, n = 14). Animals were sacrificed two days after inducing peritonitis. Serum was analyzed for biochemical parameters. Mouse peritoneal macrophages (MPMs) were harvested and analyzed for lipid content. Livers were harvested for histopathological analysis of steatosis, lipid content, and the expression of steatosis-related factors at the mRNA level. In vitro experiments: MPMs were isolated from untreated E0 mice aged 8–10 weeks and were cultured and treated with either PG545 or SST0001, both at 50 µg/mL for 24 h, followed by assessment of mRNA expression of steatosis related factors. Results: Heparanase inhibition significantly attenuated the development of liver steatosis, as was evident by liver histology and lipid content. Serum analysis indicated lowering of cholesterol and triglycerides levels in mice treated with heparanase inhibitors. In liver tissue, assessment of mRNA expression of key factors in lipid uptake, lipolysis, lipogenesis, and beta-oxidation exhibited significant downregulation following PG545 treatment and to a lesser extent when SST0001 was applied. However, in vitro treatment of MPMs with PG545, but not SST0001, resulted in increased lipid content in these cells, which is opposed to their effect on MPMs of treated mice. This may indicate distinct regulatory pathways in the system or isolated macrophages following heparanase inhibition. Conclusion: Heparanase inhibition significantly attenuates the development of liver steatosis by decreasing tissue lipid content and by affecting the mRNA expression of key lipid metabolism regulators.
Does Repeated Dosing of Intravenous Ferric Carboxymaltose Alleviate Symptoms of Restless Legs Syndrome?
Authors: Park Hea Ree , Choi Su Jung , Joo Eun Yeon
Published: March 2022

Background: Several studies have reported the efficacy of intravenous (IV) iron for patients with restless legs syndrome (RLS), but little is known about the efficacy or safety of repeated IV iron treatment. The aim of this study was to evaluate the effectiveness of repeated doses of IV ferric carboxymaltose (FCM) in treating RLS symptoms. Methods: Patients who received FCM more than twice for RLS from April 2016 to January 2020 were retrospectively reviewed. Patients who had shown positive response to initial IV FCM re-visited the clinic when their symptoms returned, and received repeated IV FCM (1000 mg). Blood iron panels were measured before initial and repeated IV FCM. We defined ‘responders’ as patients with a greater than 40% decrease in International Restless Legs Study Group Severity Scale (IRLS) compared with pre-treatment levels. Results: A total of 42 patients, including 26 with primary RLS, 5 with gastrectomy, and 11 with anemia, completed the evaluation. Patients received IV FCM infusion 2–4 times. A total of 21 of 26 (80.8%) primary cases of RLS, 4 of 5 (80.0%) patients with a history of gastrectomy, and 9 of 11 (81.8%) patients with anemia responded to repeated FCM treatment. Serum ferritin levels of patients with primary RLS were higher before the second treatment than the baseline levels. There were no serious adverse events observed in the study. Conclusions: Repeated IV FCM for recurring symptoms is an effective treatment for primary RLS and RLS associated with iron deficiency. Serum ferritin might not be a reliable factor to monitor the sustained effects of IV iron for RLS.
The Deployment of a Newly Developed Proximal Release-Type Colonic Stent Is Feasible for Malignant Colorectal Obstruction near the Anal Verge: A Single-Center Preliminary Study
Authors: Wada Kaoru , Kuwai Toshio , Sugata Syuhei , Hamada Takuro , Moriuchi Riho , Tamaru Yuzuru , Kusunoki Ryusaku , Yamaguchi Atsushi , Kouno Hirotaka , Ishaq Sauid , Kohno Hiroshi
Published: March 2022

Introduction: Colonic self-expandable metallic stents are widely used to treat malignant colorectal obstructions. Stent placement in lesions near the dentate line causes problems, including severe pain due to difficulty in positioning the stent accurately. Therefore, a proximal release-type stent was developed to overcome this issue, and this preliminary study aimed to investigate its efficacy and safety. Patients and Methods: This research enrolled eight patients with malignant colorectal obstructions up to 10 cm from the anal verge who required placement of the newly developed proximal release-type colonic stent. The primary outcome was the clinical success rate, and the secondary outcomes were the technical success and adverse events rates. Results: The technical and clinical success rates were 87.5% each, and the mean procedure time was 25.5 ± 22.0 min. The mean procedure time in the rectosigmoid colon was significantly longer than that in the rectum. Only one (12.5%) patient had stent migration, and neither anal pain nor tenesmus was observed. Discussion: The stent was highly effective in treating lesions near the anal verge, and it might contribute to the expansion of indications for colorectal stents for lesions near the dentate line. However, the indications for rectosigmoid colon lesions should be cautiously considered.
Alteration of Serum Proteome in Levo-Thyroxine-Euthyroid Thyroidectomized Patients
Authors: Landi Claudia , Cantara Silvia , Shaba Enxhi , Vantaggiato Lorenza , Marzocchi Carlotta , Maino Fabio , Bombardieri Alessio , Carleo Alfonso , Di Giuseppe Fabrizio , Angelucci Stefania , Bini Luca , Castagna Maria Grazia
Published: March 2022

The monotherapy with levo-thyroxine (LT4) is the treatment of choice for patients with hypothyroidism after thyroidectomy. However, many athyreotic LT4-treated patients with thyroid hormones in the physiological range experience hypothyroid-like symptoms, showing post-operative, statistically significant lower FT3 levels with respect to that before total thyroidectomy. Since we hypothesized that the lower plasmatic FT3 levels observed in this subgroup could be associated with tissue hypothyroidism, here we compared, by a preliminary proteomic analysis, eight sera of patients with reduced post-surgical FT3 to eight sera from patients with FT3 levels similar to pre-surgery levels, and six healthy controls. Proteomic analysis highlights a different serum protein profile among the considered conditions. By enrichment analysis, differential proteins are involved in coagulation processes (PLMN-1.61, -1.98 in reduced vs. stable FT3, p < 0.02; A1AT fragmentation), complement system activation (CFAH + 1.83, CFAB + 1.5, C1Qb + 1.6, C1S + 7.79 in reduced vs. stable FT3, p < 0.01) and in lipoprotein particles remodeling (APOAI fragmentation; APOAIV + 2.13, p < 0.003), potentially leading to a pro-inflammatory response. This study suggests that LT4 replacement therapy might restore biochemical euthyroid conditions in thyroidectomized patients, but in some cases without re-establishing body tissue euthyroidism. Since our results, this condition is reflected by the serum protein profile.
Long-Term Risk of Colectomy in Patients with Severe Ulcerative Colitis Responding to Intravenous Corticosteroids or Infliximab
Authors: De Cristofaro Elena , Salvatori Silvia , Marafini Irene , Zorzi Francesca , Alfieri Norma , Musumeci Martina , Calabrese Emma , Monteleone Giovanni
Published: March 2022

Background and aims: Intravenous corticosteroids (IVCS) and rescue therapy with infliximab (IFX) are useful for managing patients with acute severe ulcerative colitis (ASUC). However, nearly one fifth of responders undergo colectomy. Predictive factors of colectomy in this subset of patients are not fully known. We retrospectively examined the long-term risk and the predictors of colectomy in ASUC patients achieving clinical remission following treatment with IVCS or IFX. Patients and methods: Clinical and demographic characteristics were evaluated in consecutive ASUC patients who were admitted to the “Tor Vergata University” hospital between 2010 and 2020 and responded to IVCS or IFX. A multivariate logistic regression model was constructed to identify independent predictors of colectomy. Results: A total of 116 ASUC patients responding to IVCS (98 patients) or IFX (18 patients) were followed up for a median of 46 months. After discharge, 29 patients (25%) underwent colectomy. Multivariate analysis showed that a serum albumin level <3 g/dL and colonic dilation >5.5 cm on admission were independent predictors of colectomy (OR: 6.9, 95% CI: 2.08–22.8, and OR 8.5, 95% CI: 1.23–58.3, respectively). Patients with both these factors had a risk of colectomy 13 times greater than those with no risk factor. Conclusions: A low serum albumin level and colonic dilation are risk factors of long-term colectomy in ASUC patients responding to IVCS or IFX.
Evaluation of the Use of Dual Antiplatelet Therapy beyond the First Year after Acute Coronary Syndrome
Authors: Bonanad Clara , Raposeiras-Roubin Sergio , García-Blas Sergio , Núñez-Gil Iván , Vergara-Uzcategui Carlos , Díez-Villanueva Pablo , Bañeras Jordi , Badía Molins Clara , Aboal Jaime , Carreras Jose , Bodi Vicente , Gabaldón-Pérez Ana , Mateus-Porta Gemma , Parada Barcia Jose , Martínez-Sellés Manuel , Chorro Francisco , Ariza-Solé Albert
Published: March 2022

Clinical practice guidelines recommend extending dual antiplatelet therapy (DAPT) beyond 1 year after acute coronary syndrome (ACS) in patients with high ischemic risk and without high bleeding risk. The aim of this study was to identify variables associated with DAPT prolongation in a cohort of 1967 consecutive patients discharged after ACS without thrombotic or hemorrhagic events during the following year. The sample was stratified according to whether DAPT was extended beyond 1 year, and the factors associated with this strategy were analyzed. In 32.2% of the patients, DAPT was extended beyond 1 year. Overall, 770 patients (39.1%) were considered candidates for extended treatment based on PEGASUS criteria and absence of high bleeding risk, and DAPT was extended in 34.4% of them. The presence of a PEGASUS criterion was associated with extended DAPT in the univariate analysis, but not history of bleeding or a high bleeding risk. In the multivariate analysis, a history of percutaneous coronary intervention (odds ratio (OR) = 1.8, 95% confidence interval (CI) 1.4–2.4), stent thrombosis (OR = 3.8, 95% CI 1.7–8.9), coronary artery disease complexity (OR = 1.3, 95% CI 1.1–1.5), reinfarction (OR = 4.1, 95% CI 1.6–10.4), and clopidogrel use (OR = 1.3, 95% CI 1.1–1.6) were significantly associated with extended use. DAPT was extended in 32.2% of patients who survived ACS without thrombotic or hemorrhagic events. This percentage was 34.4% when the candidates were analyzed according to clinical guidelines. Neither the PEGASUS criteria nor the bleeding risk was independently associated with this strategy.
The Association between Two-Stage Tourniquet Application during Total Knee Replacement and Blood Loss: A Retrospective Cohort Study
Authors: Oh Min Seok , Kim Ji-Yoon , Kim Cho Long , Koh Su Rim , Jung Yundo , Kim Na Yeon , Jeong Mi Ae
Published: March 2022

Tourniquet use during total knee arthroplasty improves the surgical field, but is associated with several complications. The medical records of 506 patients who underwent elective total knee arthroplasty or total knee replacement from January 2017 to December 2020 were reviewed. A total of 331 patients who had undergone total knee arthroplasty were included. In the first half course group, the tourniquet was inflated with a pressure of 300 mmHg after manual banding before the incision and deflated after cement insertion. In the two-stage group, the tourniquet was inflated and deflated at the same stages of the procedure as in the first half course group. However, in this second group, the tourniquet was deflated for 15 min and then inflated again, and, finally, it was deflated after skin closure. The estimated blood loss, the number of patients who needed medications to control their blood pressure, and opioid usage at the post-anesthesia care unit were similar in both groups. The two-stage tourniquet technique was not related to reduced total blood loss in total knee arthroplasty.
Effects of Alberta Family Integrated Care (FICare) on Preterm Infant Development: Two Studies at 2 Months and between 6 and 24 Months Corrected Age
Authors: Moe Amanda M. , Kurilova Jana , Afzal Arfan R. , Benzies Karen M.
Published: March 2022

Preterm infants are at increased risk for developmental delays. Family integrated care (FICare) is a novel care delivery model that integrates parents into their infant’s care in the neonatal intensive care unit. Two follow-up studies are presented to identify effects of Alberta FICare™ on the development of preterm infants born between 32 and 34 weeks of gestation. Data for Study 1 were collected at an age of 2 months, and between 6 and 24 months for Study 2. In Study 1, Ages and Stages Questionnaires (ASQ) and maternal psychosocial distress measures were completed by 330 mothers of 387 infants (FICare, n = 223; standard care, n = 164). Study 2 utilised an additional measure, the Parent–Child Interaction Teaching Scale, with 50 mothers of 61 infants (FICare, n = 30; standard care, n = 31). For Study 1, there was no effect of Alberta FICare™ on the ASQ domains of communication, problem solving, or personal–social at an age of 2 months. For Study 2, the risk of communication delay was significantly lower for infants in Alberta FICare™ compared with standard care. Results from Study 2 suggest a possible protective effect of Alberta FICare™ for the risk of communication delays between 6 and 24 months. Further investigation into the effect of Alberta FICare™ on parent–child interactions and implications for long-term development is warranted.