bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible Role of GnIH as a Novel Link between Hyperphagia-Induced Obesity-Related Metabolic Derangements and Hypogonadism in Male Mice
Authors: Luo Rongrong , Chen Lei , Song Xingxing , Zhang Xin , Xu Wenhao , Han Dongyang , Zuo Jianyu , Hu Wen , Shi Yan , Cao Yajie , Ma Runwen , Liu Chengcheng , Xu Changlin , Li Zixin , Li Xun
Published: July 2022

Gonadotropin-inhibitory hormone (GnIH) is a reproductive inhibitor and an endogenous orexigenic neuropeptide that may be involved in energy homeostasis and reproduction. However, whether GnIH is a molecular signal link of metabolism and the reproductive system, and thus, regulates reproductive activity as a function of the energy state, is still unknown. In the present study, we investigated the involvement of GnIH in glycolipid metabolism and reproduction in vivo, and in the coupling between these two processes in the testis level. Our results showed that chronic intraperitoneal injection of GnIH into male mice not only increased food intake and altered meal microstructure but also significantly elevated body mass due to the increased mass of liver and epididymal white adipose tissue (eWAT), despite the loss of testicular weight. Furthermore, chronic intraperitoneal administration of GnIH to male mice resulted in obesity-related glycolipid metabolic derangements, showing hyperlipidemia, hyperglycemia, glucose intolerance, and insulin resistance through changes in the expression of glucose and lipid metabolism-related genes in the pancreas and eWAT, respectively. Interestingly, the expression of GnIH and GPR147 was markedly increased in the testis of mice under conditions of energy imbalance, such as fasting, acute hypoglycemia, and hyperglycemia. In addition, chronic GnIH injection markedly inhibited glucose and lipid metabolism of mice testis while significantly decreasing testosterone synthesis and sperm quality, inducing hypogonadism. These observations indicated that orexigenic GnIH triggers hyperphagia-induced obesity-related metabolic derangements and hypogonadism in male mice, suggesting that GnIH is an emerging candidate for coupling metabolism and fertility by involvement in obesity and metabolic disorder-induced reproductive dysfunction of the testes.
Remodeling of the Lamina Cribrosa: Mechanisms and Potential Therapeutic Approaches for Glaucoma
Authors: Strickland Ryan G. , Garner Mary Anne , Gross Alecia K. , Girkin Christopher A.
Published: July 2022

Glaucomatous optic neuropathy is the leading cause of irreversible blindness in the world. The chronic disease is characterized by optic nerve degeneration and vision field loss. The reduction of intraocular pressure remains the only proven glaucoma treatment, but it does not prevent further neurodegeneration. There are three major classes of cells in the human optic nerve head (ONH): lamina cribrosa (LC) cells, glial cells, and scleral fibroblasts. These cells provide support for the LC which is essential to maintain healthy retinal ganglion cell (RGC) axons. All these cells demonstrate responses to glaucomatous conditions through extracellular matrix remodeling. Therefore, investigations into alternative therapies that alter the characteristic remodeling response of the ONH to enhance the survival of RGC axons are prevalent. Understanding major remodeling pathways in the ONH may be key to developing targeted therapies that reduce deleterious remodeling.
Targeting VIP and PACAP Receptor Signaling: New Insights into Designing Drugs for the PACAP Subfamily of Receptors
Authors: Lu Jessica , Piper Sarah J. , Zhao Peishen , Miller Laurence J. , Wootten Denise , Sexton Patrick M.
Published: July 2022

Pituitary Adenylate Cyclase-Activating Peptide (PACAP) and Vasoactive Intestinal Peptide (VIP) are neuropeptides involved in a diverse array of physiological and pathological processes through activating the PACAP subfamily of class B1 G protein-coupled receptors (GPCRs): VIP receptor 1 (VPAC1R), VIP receptor 2 (VPAC2R), and PACAP type I receptor (PAC1R). VIP and PACAP share nearly 70% amino acid sequence identity, while their receptors PAC1R, VPAC1R, and VPAC2R share 60% homology in the transmembrane regions of the receptor. PACAP binds with high affinity to all three receptors, while VIP binds with high affinity to VPAC1R and VPAC2R, and has a thousand-fold lower affinity for PAC1R compared to PACAP. Due to the wide distribution of VIP and PACAP receptors in the body, potential therapeutic applications of drugs targeting these receptors, as well as expected undesired side effects, are numerous. Designing selective therapeutics targeting these receptors remains challenging due to their structural similarities. This review discusses recent discoveries on the molecular mechanisms involved in the selectivity and signaling of the PACAP subfamily of receptors, and future considerations for therapeutic targeting.
Down Regulation of Catsper1 Expression by Calmodulin Inhibitor (Calmidazolium): Possible Implications for Fertility
Authors: Forero-Forero Angela , López-Ramírez Stephany , Felix Ricardo , Hernández-Sánchez Javier , Tesoro-Cruz Emiliano , Orozco-Suárez Sandra , Murbartián Janet , Soria-Castro Elizabeth , Olivares Aleida , Bekker-Méndez Carolina , Paredes-Cervantes Vladimir , Oviedo Norma
Published: July 2022

The CatSper channel localizes exclusively in the flagella of sperm cells. The Catsper1 protein, together with three pore units, is essential for the CatSper Channel formation, which produces flagellum hyperactivation and confers sperm fertility. Catsper1 expression is dependent on Sox transcription factors, which can recognize in vitro at least three Sox binding sites on the promoter. Sox transcription factors have calmodulin-binding domains for nuclear importation. Calmodulin (CaM) is affected by the specific inhibitor calmidazolium (CMZ), which prevents the nuclear transport of Sox factors. In this work, we assess the regulation of the Catsper1 promoter in vivo by Sox factors in the murine testis and evaluate the effects of the inhibitor calmidazolium on the expression of the Casper genes, and the motility and fertility of the sperm. Catsper1 promoter has significant transcriptional activity in vivo; on the contrary, three Sox site mutants in the Catsper1 promoter reduced transcriptional activity in the testis. CaM inhibition affects Sox factor nuclear transport and has notable implications in the expression and production of Catsper1, as well as in the motility and fertility capability of sperm. The molecular mechanism described here might conform to the basis of a male contraceptive strategy acting at the transcriptional level by affecting the production of the CatSper channel, a fundamental piece of male fertility.
Distinct Patterns of GR Transcriptional Regulation in Liver and Muscle of LPS-Challenged Weaning Piglets
Authors: Liu Jie , Jiang Yidan , Jiang Zheng , Feng Yue , Zhao Ruqian
Published: July 2022

Glucocorticoid receptor (GR), which is ubiquitously expressed in nearly all cell types of various organs, mediates the tissue-specific metabolic and immune responses to maintain homeostasis and ensure survival under stressful conditions or pathological challenges. The neonatal period is metabolically demanding, and piglets are subjected to multiple stressors in modern intensive farms, especially around weaning. The liver is more responsive to LPS challenge compared to muscle, which is indicated by significantly increased TLR4 and p-p65, TNF-α, and IL-6 levels in association with GR down-regulation at both mRNA and protein levels. GR binding to the putative nGRE on TNF-α and IL-6 gene promoters decreased in the liver, but not muscle, upon LPS stimulation. The transcriptional regulation of GR also showed striking differences between liver and muscle. GR exon 1 mRNA variants 1–4, 1–5, and 1–6 were down-regulated in both liver and muscle, but a significant up-regulation of GR exon 1–9/10 mRNA variants abolished the change of total GR mRNA in the muscle in response to LPS stimulation. The significant down-regulation of GR in the liver corresponded with significantly decreased binding of p-GR and diminished histone acetylation in GR gene promoters. These results indicate that tissue-specific GR transcriptional regulation is involved in the differential inflammation responses between liver and muscle.
Examination of Trace Metals and Their Potential Transplacental Transfer in Pregnancy
Authors: Jagodić Jovana , Pavlović Slađan , Borković-Mitić Slavica , Perović Milan , Miković Željko , Đurđić Slađana , Manojlović Dragan , Stojsavljević Aleksandar
Published: July 2022

With the ever-growing concern for human health and wellbeing, the prenatal period of development requires special attention since fetuses can be exposed to various metals through the mother. Therefore, this study explored the status of selected toxic (Pb, Cd, Ni, As, Pt, Ce, Rb, Sr, U) and essential trace metals (Mn, Co, Cu, Zn, Se) in the umbilical cord (UC) sera, maternal sera, and placental tissue samples of 92 healthy women with normal pregnancies. A further aim focuses on the potential transplacental transfer of these trace metals. Based on the obtained levels of investigated elements in clinical samples, it was observed that all of the trace metals cross the placental barrier and reach the fetus. Furthermore, statistical analysis revealed significant differences in levels of toxic Ni, As, Cd, U, Sr, Rb, and essential Mn, Cu, and Zn between all three types of analyzed clinical samples. Correlation analysis highlighted As to be an element with levels that differed significantly between all tested samples. Principal component analysis (PCA) was used to enhance these findings. PCA demonstrated that Cd, Mn, Zn, Rb, Ce, U, and Sr were the most influential trace metals in distinguishing placenta from maternal and UC serum samples. As, Co, and Cu were responsible for the clustering of maternal serum samples, and PCA demonstrated that the Pt level in UC sera was responsible for the clustering of these samples. Overall, the findings of this study could contribute to a better understanding of transplacental transfer of these trace metals, and shed a light on overall levels of metal exposure in the population of healthy pregnant women and their fetuses.
Clinical and Functional Study of a De Novo Variant in the PVP Motif of Kv1.1 Channel Associated with Epilepsy, Developmental Delay and Ataxia
Authors: Dinoi Giorgia , Morin Michael , Conte Elena , Mor Shaked Hagar , Coppola Maria Antonietta , D’Adamo Maria Cristina , Elpeleg Orly , Liantonio Antonella , Hartmann Inbar , De Luca Annamaria , Blunck Rikard , Russo Angelo , Imbrici Paola
Published: July 2022

Mutations in the KCNA1 gene, encoding the voltage-gated potassium channel Kv1.1, have been associated with a spectrum of neurological phenotypes, including episodic ataxia type 1 and developmental and epileptic encephalopathy. We have recently identified a de novo variant in KCNA1 in the highly conserved Pro-Val-Pro motif within the pore of the Kv1.1 channel in a girl affected by early onset epilepsy, ataxia and developmental delay. Other mutations causing severe epilepsy are located in Kv1.1 pore domain. The patient was initially treated with a combination of antiepileptic drugs with limited benefit. Finally, seizures and ataxia control were achieved with lacosamide and acetazolamide. The aim of this study was to functionally characterize Kv1.1 mutant channel to provide a genotype–phenotype correlation and discuss therapeutic options for KCNA1-related epilepsy. To this aim, we transfected HEK 293 cells with Kv1.1 or P403A cDNAs and recorded potassium currents through whole-cell patch-clamp. P403A channels showed smaller potassium currents, voltage-dependent activation shifted by +30 mV towards positive potentials and slower kinetics of activation compared with Kv1.1 wild-type. Heteromeric Kv1.1+P403A channels, resembling the condition of the heterozygous patient, confirmed a loss-of-function biophysical phenotype. Overall, the functional characterization of P403A channels correlates with the clinical symptoms of the patient and supports the observation that mutations associated with severe epileptic phenotype cluster in a highly conserved stretch of residues in Kv1.1 pore domain. This study also strengthens the beneficial effect of acetazolamide and sodium channel blockers in KCNA1 channelopathies.
Mitochondrial Oxidative Stress Induces Cardiac Fibrosis in Obese Rats through Modulation of Transthyretin
Authors: Martínez-Martínez Ernesto , Fernández-Irigoyen Joaquín , Santamaría Enrique , Nieto María Luisa , Bravo-San Pedro José Manuel , Cachofeiro Victoria
Published: July 2022

A proteomic approach was used to characterize potential mediators involved in the improvement in cardiac fibrosis observed with the administration of the mitochondrial antioxidant MitoQ in obese rats. Male Wistar rats were fed a standard diet (3.5% fat; CT) or a high-fat diet (35% fat; HFD) and treated with vehicle or MitoQ (200 μM) in drinking water for 7 weeks. Obesity modulated the expression of 33 proteins as compared with controls of the more than 1000 proteins identified. These include proteins related to endoplasmic reticulum (ER) stress and oxidative stress. Proteomic analyses revealed that HFD animals presented with an increase in cardiac transthyretin (TTR) protein levels, an effect that was prevented by MitoQ treatment in obese animals. This was confirmed by plasma levels, which were associated with those of cardiac levels of both binding immunoglobulin protein (BiP), a marker of ER stress, and fibrosis. TTR stimulated collagen I production and BiP in cardiac fibroblasts. This upregulation was prevented by the presence of MitoQ. In summary, the results suggest a role of TTR in cardiac fibrosis development associated with obesity and the beneficial effects of treatment with mitochondrial antioxidants.
Metformin Enhances the Anti-Cancer Efficacy of Sorafenib via Suppressing MAPK/ERK/Stat3 Axis in Hepatocellular Carcinoma
Authors: Siddharth Sumit , Kuppusamy Panjamurthy , Wu Qitong , Nagalingam Arumugam , Saxena Neeraj K. , Sharma Dipali
Published: July 2022

Hepatocellular carcinoma (HCC) incidence, as well as related mortality, has been steadily increasing in the USA and across the globe, partly due to the lack of effective therapeutic options for advanced HCC. Though sorafenib is considered standard-of-care for advanced HCC, it only improves median survival by a few months when compared to placebo. Sorafenib is also associated with several unpleasant side effects that often lead to early abatement of therapy. Here, we investigate whether a combination regimen including low-dose sorafenib and a non-toxic dose of anti-diabetic drug metformin can achieve effective inhibition of HCC. Indeed, combining metformin with low-dose sorafenib inhibited growth, proliferation, migration, and invasion potential of HCC cells. We observed a 5.3- and 1.9-fold increase in sub-G1 population in the combination treatment compared to sorafenib alone. We found that the combination of metformin enhanced the efficacy of sorafenib and inhibited the MAPK/ERK/Stat3 axis. Our in vivo studies corroborated the in vitro findings, and mice harboring HepG2-derived tumors showed effective tumor reduction upon treatment with low-dose sorafenib and metformin combination. This work sheds light on a therapeutic strategy aiming to augment sorafenib efficacy or dose-de-escalation that may prove beneficial in circumventing sorafenib resistance as well as minimizing related side effects.
Synthesis and Biological Studies of Novel Aminophosphonates and Their Metal Carbonyl Complexes (Fe, Ru)
Authors: Kosińska Aneta , Virieux David , Pirat Jean-Luc , Czarnecka Kamila , Girek Małgorzata , Szymański Paweł , Wojtulewski Sławomir , Vasudevan Saranya , Chworos Arkadiusz , Rudolf Bogna
Published: July 2022

The quest to find new inhibitors of biologically relevant targets is considered an important strategy to introduce new drug candidates for the treatment of neurodegenerative diseases. A series of (aminomethyl)benzylphosphonates 8a–c and their metallocarbonyl iron 9a–c and ruthenium 10a–c complexes were designed, synthesized, and evaluated for their inhibitory potentials against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) by determination of IC50. Metallocarbonyl derivatives, in general, did not show significant inhibition activity against these enzymes, the most potent inhibitor was the (aminomethyl)benzylphosphonate 8a (IC50 = 1.215 µM against AChE). Molecular docking analysis of AChE and (aminomethyl)benzylphosphonates 8a–c showed the strongest interactions of 8a and AChE compared to isomers 8b and 8c. Cytotoxicity studies of synthesized compounds towards the V79 cell line were also performed and discussed.
Evolution of the Membrane Transport Protein Domain
Authors: Dabravolski Siarhei A. , Isayenkov Stanislav V.
Published: July 2022

Membrane transport proteins are widely present in all living organisms, however, their function, transported substrate, and mechanism of action are unknown. Here we use diverse bioinformatics tools to investigate the evolution of MTPs, analyse domain organisation and loop topology, and study the comparative alignment of modelled 3D structures. Our results suggest a high level of conservancy between MTPs from different taxa on both amino acids and structural levels, which imply some degree of functional similarities. The presence of loop/s of different lengths in various positions suggests tax-on-specific adaptation to transported substrates, intracellular localisation, accessibility for post-translation modifications, and interaction with other proteins. The comparison of modelled structures proposes close relations and a common origin for MTP and Na/H exchanger. Further, a high level of amino acid similarity and identity between archaeal and bacterial MTPs and Na/H exchangers imply conservancy of ion transporting function at least for archaeal and bacterial MTPs.
Three-Dimensional Culture of Cartilage Tissue on Nanogel-Cross-Linked Porous Freeze-Dried Gel Scaffold for Regenerative Cartilage Therapy: A Vibrational Spectroscopy Evaluation
Authors: Adachi Tetsuya , Miyamoto Nao , Imamura Hayata , Yamamoto Toshiro , Marin Elia , Zhu Wenliang , Kobara Miyuki , Sowa Yoshihiro , Tahara Yoshiro , Kanamura Narisato , Akiyoshi Kazunari , Mazda Osam , Nishimura Ichiro , Pezzotti Giuseppe
Published: July 2022

This study presents a set of vibrational characterizations on a nanogel-cross-linked porous freeze-dried gel (NanoCliP-FD gel) scaffold for tissue engineering and regenerative therapy. This scaffold is designed for the in vitro culture of high-quality cartilage tissue to be then transplanted in vivo to enable recovery from congenital malformations in the maxillofacial area or crippling jaw disease. The three-dimensional scaffold for in-plate culture is designed with interface chemistry capable of stimulating cartilage formation and maintaining its structure through counteracting the dedifferentiation of mesenchymal stem cells (MSCs) during the formation of cartilage tissue. The developed interface chemistry enabled high efficiency in both growth rate and tissue quality, thus satisfying the requirements of large volumes, high matrix quality, and superior mechanical properties needed in cartilage transplants. We characterized the cartilage tissue in vitro grown on a NanoCliP-FD gel scaffold by human periodontal ligament-derived stem cells (a type of MSC) with cartilage grown by the same cells and under the same conditions on a conventional (porous) atelocollagen scaffold. The cartilage tissues produced by the MSCs on different scaffolds were comparatively evaluated by immunohistochemical and spectroscopic analyses. Cartilage differentiation occurred at a higher rate when MSCs were cultured on the NanoCliP-FD gel scaffold compared to the atelocollagen scaffold, and produced a tissue richer in cartilage matrix. In situ spectroscopic analyses revealed the cell/scaffold interactive mechanisms by which the NanoCliP-FD gel scaffold stimulated such increased efficiency in cartilage matrix formation. In addition to demonstrating the high potential of human periodontal ligament-derived stem cell cultures on NanoCliP-FD gel scaffolds in regenerative cartilage therapy, the present study also highlights the novelty of Raman spectroscopy as a non-destructive method for the concurrent evaluation of matrix quality and cell metabolic response. In situ Raman analyses on living cells unveiled for the first time the underlying physiological mechanisms behind such improved chondrocyte performance.
Halochromic Behavior and Anticancer Effect of New Synthetic Anthocyanidins Complexed with β-Cyclodextrin Derivatives
Authors: Păușescu Iulia , Kántor Izolda , Babos György , May Zoltán , Fodor-Kardos Andrea , Miskolczy Zsombor , Biczók László , Péter Francisc , Medeleanu Mihai , Feczkó Tivadar
Published: July 2022

Anthocyanidins, the aglycons of anthocyanins, are known, beyond their function in plants, also as compounds with a wide range of biological and pharmacological activities, including cytostatic effect against various cancer cells. The nature and position of the substituents in the flavylium cation is essential for such biological properties, as well as the equilibrium between the multistate of the different chemical species that are generated by the flavylium cation, including quinoidal base, hemiketal, and cis- and trans-chalcones. In this work, eight new flavylium derivatives were synthesized, characterized for confirmation of the structure by FT-IR and 2D-NMR, and investigated in vitro as possible cytostatic compounds against HCT116 and HepG2 cancer cells. The most active two compounds were explored for their halochromic properties that can influence the biological activity and subjected to molecular encapsulation in β-cyclodextrin derivatives in order to increase their solubility in water and bioavailability. The anticancer effect was influenced by the position (6-, 7-, or 8-) of the methoxy group in the β-ring of the methoxy-4′-hydroxy-3′-methoxyflavylium cation, while the study of the halochromic properties revealed the important role played by the chalcone species of the pH-dependent multistate in both the uncomplexed and inclusion complex forms of these anthocyanidins.
Prioritisation of Adverse Drug Events Leading to Hospital Admission and Occurring during Hospitalisation: A RAND Survey
Authors: Haerdtlein Annette , Boehmer Anna Maria , Karsten Dafonte Katharina , Rottenkolber Marietta , Jaehde Ulrich , Dreischulte Tobias
Published: July 2022

(1) Adverse drug events (ADEs) are a common cause of emergency department visits and occur frequently during hospitalisation. Instruments that facilitate the detection of the most relevant ADEs could lead to a more targeted and efficient use of limited resources in research and practice. (2) We conducted two consensus processes based on the RAND/UCLA appropriateness method, in order to prioritise ADEs leading to hospital admission (panel 1) and occurring during hospital stay (panel 2) for inclusion in future ADE measurement instruments. In each panel, the experts were asked to assess the “overall importance” of each ADE on a four-point Likert scale (1 = not important to 4 = very important). ADEs with a median rating of ≥3 without disagreement were defined as “prioritised“. (3) The 13 experts in panel 1 prioritised 38 out of 65 ADEs, while the 12 experts in panel 2 prioritised 34 out of 63 ADEs. The highest rated events were acute kidney injury and hypoglycaemia (both panels), as well as Stevens–Johnson syndrome in panel 1 and rhabdomyolysis in panel 2. (4) The survey led to a set of ADEs for which there was consensus that they were of particular importance as presentations of acute medication-related harm, thereby providing a focus for further medication safety research and clinical practice.
Does Aerobic plus Machine-Assisted Resistance Training Improve Vascular Function in Type 2 Diabetes? A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Trial Sequential Analysis
Authors: Guo Xianshan , Guo Shizhe , Zhang Hongmei , Li Zhen
Published: July 2022

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia, insulin resistance, and pancreatic B cell dysfunction. Hyperglycemia can cause several complications, including nephrological, neurological, ophthalmological, and vascular complications. Many modalities, such as medication, physical therapies, and exercise, are developed against vascular disorders. Among all exercise forms, aerobic plus machine-assisted resistance training is widely applied. However, whether this intervention can significantly improve vascular conditions remains controversial. In this study, an electronic search was processed for the Pubmed, Embase, and Cochrane libraries for randomized controlled trials (RCTs) comparing the efficacy of aerobic plus machine-assisted resistance training with no exercise (control) on patients with T2DM. Pulse wave velocity (PWV), the index of arterial stiffness, was chosen as primary outcome. The reliability of the pooled outcome was tested by trial sequential analysis (TSA). Secondary outcomes included systolic blood pressure (SBP) and hemoglobin A1c (HbA1c). Finally, five RCTs with a total of 328 patients were included. Compared with control, aerobic plus machine-assisted resistance training failed to provide significant improvement on PWV (MD −0.54 m/s, 95% CI [−1.69, 0.60], p = 0.35). On the other hand, TSA indicated that this results till needs more verifications. Additionally, this training protocol did not significantly decrease SBP (MD −1.05 mmHg, 95% CI [−3.71, 1.61], p = 0.44), but significantly reduced the level of HbA1c (MD −0.55%, 95% CI [−0.88, −0.22], p = 0.001). In conclusion, this meta-analysis failed to detect a direct benefit of aerobic plus machine-assisted resistance training on vascular condition in T2DM population. Yet the improvement in HbA1c implied a potential of this training method in mitigating vascular damage. More studies are needed to verify the benefit.
Association between Anti-Hepatitis C Viral Intervention Therapy and Risk of Sjögren’s Syndrome: A National Retrospective Analysis
Authors: Tung Chien-Hsueh , Chen Yen-Chun , Chen Yi-Chun
Published: July 2022

Hepatitis C virus (HCV) infection is a potential risk factor for Sjögren’s syndrome (SS). However, it is unclear whether anti-HCV intervention therapy could decrease SS risk. A retrospective cohort analysis from 1997–2012 comprising 17,166 eligible HCV-infected adults was conducted. By 1:2 propensity score matching, a total of 2123 treated patients and 4246 untreated patients were subjected to analysis. The incidence rates and risks of SS and death were evaluated through to the end of 2012. In a total follow-up of 36,906 person-years, 177 (2.8%) patients developed SS, and 522 (8.2%) died during the study period. The incidence rates of SS for the treated and untreated cohorts were 5.3 vs. 4.7/1000 person-years, and those of death for the treated and untreated cohorts were 10.0 vs. 14.8/1000 person-years. A lower risk of death (adjusted hazard ratio, 0.68; 95% CI, 0.53–0.87) was present in HCV-infected patients receiving anti-HCV therapy in multivariable Cox regression, and this remained consistent in multivariable stratified analysis. However, there were no relationships between anti-HCV therapy and its therapeutic duration, and SS risk in multivariable Cox regression. In conclusion, anti-HCV intervention therapy was not associated with lower SS risk in HCV-infected patients, but associated with lower death risk.
The Dynamic Characteristics of Myocardial Contractility and Extracellular Volume in Type 2 Diabetes Mellitus Mice Investigated by 7.0T Cardiac Magnetic Resonance
Authors: Shi Chunyan , Zhang Hongkai , Zhang Nan , Liu Dongting , Fan Zhanming , Sun Zhonghua , Liu Jiayi , Xu Lei
Published: July 2022

Type 2 diabetes mellitus (T2DM) is associated with a high prevalence of diastolic dysfunction and congestive heart failure. A potential contributing factor is the accelerated accumulation of diffuse myocardial fibrosis and stiffness. Novel cardiac magnetic resonance (CMR) imaging techniques can identify both myocardial fibrosis and contractility quantitatively. This study aimed to investigate the dynamic characteristics of the myocardial strain and altered extracellular volume (ECV) fraction as determined by 7.0 T CMR in T2DM mice. C57Bl/6J mice were randomly divided into T2DM (fed a high-fat diet) and control (fed a normal diet) groups. They were scanned on 7.0 T MRI every 4 weeks until the end of week 24. The CMR protocol included multi-slice cine imaging to assess left ventricle strain and strain rate, and pre- and post-contrast T1 mapping images to quantify ECV. The ECV in the T2DM mice was significantly higher (p < 0.05) than that in the control group since week 12 with significantly impaired myocardial strain (p < 0.05). A significant linear correlation was established between myocardial strain and ECV (p < 0.001) and left ventricular-ejection fraction and ECV (p = 0.003). The results suggested that CMR feature tracking-derived myocardial strain analysis can assess functional abnormalities that may be associated with ECM alterations in diabetic cardiomyopathy, contributing to the study of diabetic therapy effects.
A Cross-Sectional Observational Study of the Relationship between Outdoor Exposure and Myopia in University Students, Measured by Conjunctival Ultraviolet Autofluorescence (CUVAF)
Authors: Bilbao-Malavé Valentina , González-Zamora Jorge , Gándara Elsa , de la Puente Miriam , Escriche Elena , Bezunartea Jaione , Marizkurrena Ainara , Alonso Elena , Hernández María , Fernández-Robredo Patricia , Sáenz de Viteri Manuel , Barrio-Barrio Jesús , García-Layana Alfredo , Recalde Sergio
Published: July 2022

Myopia is the most common refractive error worldwide. This cannot be explained by genetic factors alone, therefore, environmental factors may play an important role. Hence, the main objective of this study was to analyse whether outdoor exposure could exert a protective effect against the development of myopia in a cohort of young adults and to investigate ultraviolet autofluorescence (CUVAF), as a biomarker of time spent outdoors. A cross-sectional observational study was carried out using two cohorts. A total of 208 participants were recruited, 156 medical students and 52 environmental science students. The data showed that 66.66% of the medical students were myopic, while 50% of the environmental science students were myopic (p = 0.021). Environmental science students spent significantly more hours per week doing outdoor activities than medical students (p < 0.0001), but there was no significant difference with respect to near work activities between them. In both cohorts, the degree of myopia was inversely associated with CUVAF, and a statistically significant positive correlation was observed between spherical equivalent and CUVAF (Pearson’s r = 0.248). In conclusion, outdoor activities could reduce the onset and progression of myopia not only in children, but also in young adults. In addition, CUVAF represents an objective, non-invasive biomarker of outdoor exposure that is inversely associated with myopia.
Changes in the Mean and Variance of the Numbers of Medical Visits for Allergic Diseases before and during the COVID-19 Pandemic in Korea
Authors: Choi Hyo Geun , Kim Joo-Hee , An Yong-Hwi , Park Min Woo , Wee Jee Hye
Published: July 2022

The implementation of precautionary measures, such as wearing a mask and social distancing, may have affected allergic diseases during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to compare the numbers of medical visits for allergic diseases before and during the COVID-19 pandemic. Data were obtained from the Korean National Health Insurance claims database. Monthly numbers of patients for four allergic diseases, i.e., allergic rhinitis (AR), asthma, atopic dermatitis (AD), and allergic conjunctivitis (AC), were evaluated using ICD-10 codes and compared between the ‘before COVID-19’ period from January 2018 to February 2020, and the ‘during COVID-19’ period from March 2020 to June 2021, since the first COVID-19 patient was detected on 20 January 2020, in Korea. Subgroup analyses were performed according to age and sex. The mean numbers of medical visits for AR and asthma were significantly greater before COVID-19 than those during COVID-19 (both p < 0.001). The variance in the number of medical visits for asthma decreased during the COVID-19 pandemic. However, the mean number of medical visits for AD increased slightly during COVID-19 and that for AC did not change before and during the COVID-19 pandemic. In subgroup analyses, the results showed a similar pattern to that of the total number of participants, regardless of age and sex. In conclusion, medical visits for AR and asthma significantly decreased during the COVID-19 pandemic, regardless of age and sex.
Negative-Pressure Wound Therapy for Prevention of Sternal Wound Infection after Adult Cardiac Surgery: Systematic Review and Meta-Analysis
Authors: Biancari Fausto , Santoro Grazia , Provenzano Federica , Savarese Leonardo , Iorio Francesco , Giordano Salvatore , Zebele Carlo , Speziale Giuseppe
Published: July 2022

The results of current studies are not conclusive on the efficacy of incisional negative-pressure wound therapy (NPWT) for the prevention of sternal wound infection (SWI) after adult cardiac surgery. A systematic review of the literature was performed through PubMed, Scopus and Google to identify studies which investigated the efficacy of NPWT to prevent SWI after adult cardiac surgery. Available data were pooled using RevMan and Meta-analyst with random effect models. Out of 191 studies retrieved from the literature, ten fulfilled the inclusion criteria and were included in this analysis. The quality of these studies was judged fair for three of them and poor for seven studies. Only one study was powered to address the efficacy of NPWT for the prevention of postoperative SWI. Pooled analysis of these studies showed that NPWT was associated with lower risk of any SWI (4.5% vs. 9.0%, RR 0.54, 95% CI 0.34–0.84, I2 48%), superficial SWI (3.8% vs. 4.4%, RR 0.63, 95% CI 0.29–1.36, I2 65%), and deep SWI (1.8% vs. 4.7%, RR 0.46, 95% CI 0.26–0.74, I2 0%), but such a difference was not statistically significant for superficial SWI. When only randomized and alternating allocated studies were included, NPWT was associated with a significantly lower risk of any SWI (3.3% vs. 16.5%, RR 0.22, 95% CI 0.08–0.62, I2 0%), superficial SWI (2.6% vs. 12.4%, RR 0.21, 95% CI 0.06–0.69, I2 0%), and deep SWI (1.2% vs. 4.8%, RR 0.17, 95% CI 0.03–0.95, I2 0%). This pooled analysis showed that NPWT may prevent postoperative SWI after adult cardiac surgery. NPWT is expected to be particularly useful in patients at risk for surgical site infection and may significantly reduce the burden of resources needed to treat such a complication. However, the methodology of the available studies was judged as poor for most of them. Further studies are needed to obtain conclusive results on the potential benefits of this preventative strategy.
Risk of Cancer in Connective Tissue Diseases in Northeastern Italy over 15 Years
Authors: Treppo Elena , Toffolutti Federica , Manfrè Valeria , Taborelli Martina , De Marchi Ginevra , De Vita Salvatore , Serraino Diego , Quartuccio Luca
Published: July 2022

Objective: To evaluate cancer risk among individuals with connective tissue disease (CTD) in Friuli Venezia Giulia, northern Italy. Methods: A population-based cohort study was conducted based on data from health records available in the regional healthcare database. Demographic characteristics, hospital discharges, exemption from medical charges, drug prescriptions, were individually matched with data from the population-based cancer registry. Cancer risk was assessed in people diagnosed with the following diseases: systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), systemic sclerosis (SSc), polymyositis (PM), and dermatomyositis (DM). Results: In all, 2504 patients were followed for a total of 18,006 person-years (median follow-up: 6.8 years). After 5 and 10 years of follow-up, the cumulative cancer incidence was 2.6% and 8.5%, respectively. The most common cancers were breast (n = 34), lung (n = 24), colon–rectum–anus (n = 20), and non-Hodgkin lymphomas (NHL) (n = 20). Overall, no excess cancer risk was noted (SIR = 0.87), whereas the number of observed NHL cases was more than two-fold significantly higher than expected (SIR = 2.52). The subgroup analysis showed a higher risk of NHL among SS patients (SIR = 3.84) and SLE patients (SIR = 2.69). Conversely, the study population showed a decreased risk for breast cancers (SIR = 0.61) and corpus uteri (SIR = 0.21). Conclusions: The incidence of NHL was higher among patients with SS and SLE. Careful surveillance for hematological malignancies in these patients is recommended.
Establishing a Learning Model for Correct Hand Hygiene Technique in a NICU
Authors: Németh Irén A. Kopcsóné , Nádor Csaba , Szilágyi László , Lehotsky Ákos , Haidegger Tamás
Published: July 2022

The ability of healthcare workers to learn proper hand hygiene has been an understudied area of research. Generally, hand hygiene skills are regarded as a key contributor to reduce critical infections and healthcare-associated infections. In a clinical setup, at a Neonatal Intensive Care Unit (NICU), the outcome of a multi-modal training initiative was recorded, where objective feedback was provided to the staff. It was hypothesized that staff at the NICU are more sensitive towards applying increased patient safety measures. Outcomes were recorded as the ability to cover all hand surfaces with Alcohol-Based Handrub (ABHR), modelled as a time-series of measurements. The learning ability to rub in with 1.5 mL and with 3 mL was also assessed. As a secondary outcome, handrub consumption and infection numbers were recorded. It has been observed that some staff members were able to quickly learn the proper hand hygiene, even with the limited 1.5 mL, while others were not capable of acquiring the technique even with 3 mL. When analyzing the 1.5 mL group, it was deemed an insufficient ABHR amount, while with 3 mL, the critical necessity of skill training to achieve complete coverage was documented. Identifying these individuals helps the infection control staff to better focus their training efforts. The training led to a 157% increase in handrub consumption. The setting of the study did not allow to show a measurable reduction in the number of hospital infections. It has been concluded that the training method chosen by the staff greatly affects the quality of the outcomes.
Developmental Assessment of Visual Communication Skills in Primary Education
Authors: Simon Tünde , Biró Ildikó , Kárpáti Andrea
Published: July 2022

In this paper, we describe subskills of visual communication based on the skill structure outlined in the Common European Framework of Visual Literacy. We have developed this Framework further through assessing the development of subskills related to visual communication in the “produce” and “respond” domains of CEFR-VC in primary school grades. We developed and validated online digital assessment tools to facilitate the introduction of authentic assessment as a standard practice in curriculum development. The results of this study include the definition of its components, development of innovative tools for their assessment, and description of the development of its subskills in the “produce” and “respond” domains. Our tests for the “respond” domain of the visual literacy framework were administered in the eDia interactive diagnostic testing environment in Grades 4–6 (ages 10–12 years) of the Hungarian primary school system. The tools for the second experiment about the “create” domain of visual communication were developed in the GeoGebra free educational software environment and tested major components of the “produce” domain of visual communication in primary Grades 5–8 (ages 11–14 years). Results show increasing attainment in subskills through the age groups in the “produce” domain and less significant or no development in the “respond” domain, which is underrepresented in Hungarian art education curricula. Development is unrelated to school achievement in non-art disciplines, showing the distinctiveness of the visual domain, and is weakly related to gender and digital literacy. Using our subskill descriptions and the assessment tools, teachers may select those subskills that they find most important to develop during the limited teaching time for visual arts. The paper ends with suggestions to enhance visual communication as a cross-curricular competency that develops visual-spatial intelligence.
Tip Clearance Effect on The Tip Leakage Vortex Evolution and Wake Instability of a Ducted Propeller
Authors: Zhang Xidi , Liu Zhihua , Cao Liushuai , Wan Decheng
Published: July 2022

The occurrence of a tip leakage vortex (TLV) is a special phenomenon of ducted propellers, which has a significant influence on the propeller’s hydrodynamic performance and efficiency. The inception, evolution, and instability of the TLV under different tip clearance sizes have a direct impact on the cavitation and acoustic characteristics. A simulation was set up to calculate the open-water performance of a standard ducted propeller. The open-water characteristics (OWCs) were compared with the experimental data to verify the feasibility of the method. Furthermore, to capture the influence of tip clearance size on the vortex structure evolution and wake dynamics, the improved delayed detached eddy simulation (IDDES) method was adopted to simulate four groups of ducted propellers with different tip clearances. The results showed that with the increase in the gap-to-span ratio (GSR), KTD and η0 gradually decreased, while KQ and KTB increased, but a peak point existed. Moreover, the TLV became thicker, indicating damage to the energy recycling process. The fast Fourier transform (FFT) of several wake points showed pressure pulsations of the wake ranging from the blade-passing frequency to the shaft frequency, and the evolution process accelerated with the increase in the GSR. The power spectral density (PSD) analysis showed that the energy of the wake enhanced with the increase in the GSR. In particular, the vortex interactions could cause pulses in low-GSR conditions, which could intensify the excitation force of the propeller and also have a certain impact on the noise level.
Surgeon Dominated Design Can Improve the Accuracy of Patient-Specific Instruments in Kinematically Aligned TKA
Authors: Wen Liang , Wang Zhiwei , Ma Desi , Qu Tiebing
Published: July 2022

Precise bone resection is mandatory for kinematically aligned total knee arthroplasty (KA-TKA). This study is to investigate whether surgeon-dominated design can alter the accuracy of patient-specific instrumentation (PSI) in KA-TKA compared with the engineer design. A total of 24 patients (24 knees) who underwent KA-TKA in our institution were assigned to an engineer design group (10 knees) and surgeon design group (14 knees) chronologically. A novel portable medical-engineer interactive application can greatly enhance the surgeon’s participation in PSI design. The bone resection discrepancies were used to evaluate the accuracy of PSI in bone resection. The overall discrepancy of bone resection was reduced by surgeon-designed PSI compared to engineer-designed PSI by 0.33 mm. Surgeon-designed PSI seems to reduce the outliers in terms of relative discrepancies in bone resection as well, but it does not reach statistical significance. Moreover, surgeon-designed PSI could significantly improve the accuracy of PSI in the restoration of the joint line in terms of medial proximal tibial angle and mechanical lateral distal femoral angle. This study indicates that the dominance of surgeons in both PSI design and subsequent surgical operation should be emphasized in efforts to improve the accuracy of PSI.
Cardiogenic Shock Does Not Portend Poor Long-Term Survival in Patients Undergoing Primary Percutaneous Coronary Intervention
Authors: Steinacher Eva , Hofer Felix , Kazem Niema , Hammer Andreas , Koller Lorenz , Lang Irene , Hengstenberg Christian , Niessner Alexander , Sulzgruber Patrick
Published: July 2022

Although a strong association of cardiogenic shock (CS) with in-hospital mortality in patients with acute coronary syndrome (ACS) is well established, less attention has been paid to its prognostic influence on long-term outcome. We evaluated the impact of CS in 1173 patients undergoing primary percutaneous coronary interventions between 1997 and 2009. Patients were followed up until the primary study endpoint (cardiovascular mortality) was reached. Within the entire study population, 112 (10.4%) patients presented with CS at admission. After initial survival, CS had no impact on mortality (non-CS: 23.5% vs. CS: 24.0%; p = 0.923), with an adjusted hazard ratio of 1.18 (95% CI: 0.77–1.81; p = 0.457). CS patients ≥ 55 years (p = 0.021) with moderately or severely impaired left ventricular function (LVF; p = 0.039) and chronic kidney disease (CKD; p = 0.013) had increased risk of cardiovascular mortality during follow-up. The present investigation extends currently available evidence that cardiovascular survival in CS is comparable with non-CS patients after the acute event. CS patients over 55 years presenting with impaired LVF and CKD at the time of ACS are at increased risk for long-term mortality and could benefit from personalized secondary prevention.
A Personal Prospective on Testosterone Therapy in Women—What We Know in 2022
Authors: Donovitz Gary S.
Published: July 2022

Hormone replacement therapy continues to be a controversial topic in medicine, with certain narratives regarding safety concerns that are not scientifically established in peer-reviewed literature. These negative narratives, specifically undermining the use of testosterone in women, have caused women to remain without any Food and Drug Administration (FDA)-approved testosterone therapies, while more than 30 FDA-approved testosterone therapies are available for men in the United States. This has resulted in millions of women suffering in silence with very common symptoms of perimenopause and menopause that could easily be addressed with the use of testosterone. There is growing evidence to support the use of physiologic doses of testosterone for sexual function, osteoporosis prevention, brain protection, and breast protection. The safety of testosterone use in women has been evaluated for the past 80 years. A recent publication on the complications of subcutaneous hormone-pellet therapy, looking at a large cohort of patients over 7 years, demonstrated long-term safety. In addition, there have been two large long-term peer-reviewed studies showing a significant reduction in the incidence of invasive breast cancer in women on testosterone therapy. Perhaps it is time for the FDA to consider approving products that would benefit testosterone-deficient women.
Robotic Mediastinal Tumor Resections: Position and Port Placement
Authors: Okazaki Mikio , Shien Kazuhiko , Suzawa Ken , Sugimoto Seiichiro , Toyooka Shinichi
Published: July 2022

This study aimed to determine the optimal position and port placement during robotic resection for various mediastinal tumors. For anterior mediastinal tumors, total or extended thymectomy is commonly performed in the supine position using the lateral or subxiphoid approach. Although it is unclear which approach is better during robotic thymectomy, technical advantages of subxiphoid approach are beneficial for patients with myasthenia who require extended thymectomy. Partial thymectomy is performed in the supine position using a lateral approach. Superior, middle, and posterior mediastinal tumors are resected in the decubitus position using the lateral approach, whereas dumbbell tumor resection, which requires a posterior approach, can be performed in the prone position. The position and port placement should be chosen depending on the size, location, and aggressiveness of the tumor. In this study, we describe how to choose which of these different robotic approaches can be used based on our experience and previous reports.