bluuebunny/crossref_metadata_2025 huggingface dataset:
DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases
Authors: Khoubai Fatma Zohra , Grosset Christophe F.
Published: October 2021

Mitogen-activated protein kinases (MAPKs) are essential for proper cell functioning as they regulate many molecular effectors. Careful regulation of MAPKs is therefore required to avoid MAPK pathway dysfunctions and pathologies. The mammalian genome encodes about 200 phosphatases, many of which dephosphorylate the MAPKs and bring them back to an inactive state. In this review, we focus on the normal and pathological functions of dual-specificity phosphatase 9 (DUSP9)/MAP kinase phosphatases-4 (MKP-4). This cytoplasmic phosphatase, which belongs to the threonine/tyrosine dual-specific phosphatase family and was first described in 1997, is known to dephosphorylate ERK1/2, p38, JNK and ASK1, and thereby to control various MAPK pathway cascades. As a consequence, DUSP9 plays a major role in human pathologies and more specifically in cardiac dysfunction, liver metabolic syndromes, diabetes, obesity and cancer including drug response and cell stemness. Here, we recapitulate the mechanism of action of DUSP9 in the cell, its levels of regulation and its roles in the most frequent human diseases, and discuss its potential as a therapeutic target.
The Papain-like Cysteine Protease HpXBCP3 from Haematococcus pluvialis Involved in the Regulation of Growth, Salt Stress Tolerance and Chlorophyll Synthesis in Microalgae
Authors: Liu Wenfu , Guo Chunli , Huang Danqiong , Li Hui , Wang Chaogang
Published: October 2021

The papain-like cysteine proteases (PLCPs), the most important group of cysteine proteases, have been reported to participate in the regulation of growth, senescence, and abiotic stresses in plants. However, the functions of PLCPs and their roles in stress response in microalgae was rarely reported. The responses to different abiotic stresses in Haematococcus pluvialis were often observed, including growth regulation and astaxanthin accumulation. In this study, the cDNA of HpXBCP3 containing 1515 bp open reading frame (ORF) was firstly cloned from H. pluvialis by RT-PCR. The analysis of protein domains and molecular evolution showed that HpXBCP3 was closely related to AtXBCP3 from Arabidopsis. The expression pattern analysis revealed that it significantly responds to NaCl stress in H. pluvialis. Subsequently, transformants expressing HpXBCP3 in Chlamydomonas reinhardtii were obtained and subjected to transcriptomic analysis. Results showed that HpXBCP3 might affect the cell cycle regulation and DNA replication in transgenic Chlamydomonas, resulting in abnormal growth of transformants. Moreover, the expression of HpXBCP3 might increase the sensitivity to NaCl stress by regulating ubiquitin and the expression of WD40 proteins in microalgae. Furthermore, the expression of HpXBCP3 might improve chlorophyll content by up-regulating the expression of NADH-dependent glutamate synthases in C. reinhardtii. This study indicated for the first time that HpXBCP3 was involved in the regulation of cell growth, salt stress response, and chlorophyll synthesis in microalgae. Results in this study might enrich the understanding of PLCPs in microalgae and provide a novel perspective for studying the mechanism of environmental stress responses in H. pluvialis.
Machine Learning Assisted Approach for Finding Novel High Activity Agonists of Human Ectopic Olfactory Receptors
Authors: Jabeen Amara , de March Claire A. , Matsunami Hiroaki , Ranganathan Shoba
Published: October 2021

Olfactory receptors (ORs) constitute the largest superfamily of G protein-coupled receptors (GPCRs). ORs are involved in sensing odorants as well as in other ectopic roles in non-nasal tissues. Matching of an enormous number of the olfactory stimulation repertoire to its counterpart OR through machine learning (ML) will enable understanding of olfactory system, receptor characterization, and exploitation of their therapeutic potential. In the current study, we have selected two broadly tuned ectopic human OR proteins, OR1A1 and OR2W1, for expanding their known chemical space by using molecular descriptors. We present a scheme for selecting the optimal features required to train an ML-based model, based on which we selected the random forest (RF) as the best performer. High activity agonist prediction involved screening five databases comprising ~23 M compounds, using the trained RF classifier. To evaluate the effectiveness of the machine learning based virtual screening and check receptor binding site compatibility, we used docking of the top target ligands to carefully develop receptor model structures. Finally, experimental validation of selected compounds with significant docking scores through in vitro assays revealed two high activity novel agonists for OR1A1 and one for OR2W1.
Evaluation of Therapeutic Targets in Histological Subtypes of Bladder Cancer
Authors: Wucherpfennig Sophie , Rose Michael , Maurer Angela , Cassataro Maria Angela , Seillier Lancelot , Morsch Ronja , Hammad Ehab , Baldia Philipp Heinrich , Ecke Thorsten H. , Vögeli Thomas-Alexander , Knüchel Ruth , Gaisa Nadine T.
Published: October 2021

Histologically, bladder cancer is a heterogeneous group comprising urothelial carcinoma (UC), squamous cell carcinoma, adenocarcinomas (ACs), urachal carcinomas (UrCs), and small cell neuroendocrine carcinomas (SCCs). However, all bladder cancers have been treated so far uniformly, and targeted therapy options are still limited. Thus, we aimed to determine the protein expression/molecular status of commonly used cancer targets (programmed cell death 1 ligand 1 (PD-L1), mismatch repair (MMR), androgen and estrogen receptors (AR/ER), Nectin-4, tumor-associated calcium signal transducer 2 (Tacstd2, Trop-2), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and fibroblast growth factor receptor 3 (FGFR3)) to give first insights into whether patients with SCC, AC/UrCs, and squamous-differentiated carcinomas (Sq-BLCA) of the bladder could be eligible for targeted therapies. In addition, for MMR-deficient tumors, microsatellite instability was analyzed. We completed our own data with molecular data from The Cancer Genome Atlas (TCGA). We present ratios for each drug and cumulative ratios for multiple therapeutic options for each nonurothelial subtype. For example, 58.9% of SCC patients, 33.5% of AC/UrCs patients, and 79.3% of Sq-BLCA patients would be eligible for at least one of the analyzed targets. In conclusion, our findings hold promise for targeted therapeutic approaches in selected patients in the future, as various drugs could be applied according to the biomarker status.
QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation
Authors: Bhattarai Shristi , Sugita Bruna M. , Bortoletto Stefanne M. , Fonseca Aline S. , Cavalli Luciane R. , Aneja Ritu
Published: October 2021

Triple-negative breast cancer (TNBC) can be further classified into androgen receptor (AR)-positive TNBC and AR-negative TNBC or quadruple-negative breast cancer (QNBC). Here, we investigated genomic instability in 53 clinical cases by array-CGH and miRNA expression profiling. Immunohistochemical analysis revealed that 64% of TNBC samples lacked AR expression. This group of tumors exhibited a higher level of copy number alterations (CNAs) and a higher frequency of cases affected by CNAs than TNBCs. CNAs in genes of the chromosome instability 25 (CIN25) and centrosome amplification (CA) signatures were more frequent in the QNBCs and were similar between the groups, respectively. However, expression levels of CIN25 and CA20 genes were higher in QNBCs. miRNA profiling revealed 184 differentially expressed miRNAs between the groups. Fifteen of these miRNAs were mapped at cytobands with CNAs, of which eight (miR-1204, miR-1265, miR-1267, miR-23c, miR-548ai, miR-567, miR-613, and miR-943), and presented concordance of expression and copy number levels. Pathway enrichment analysis of these miRNAs/mRNAs pairings showed association with genomic instability, cell cycle, and DNA damage response. Furthermore, the combined expression of these eight miRNAs robustly discriminated TNBCs from QNBCs (AUC = 0.946). Altogether, our results suggest a significant loss of AR in TNBC and a profound impact in genomic instability characterized by CNAs and deregulation of miRNA expression.
The Effect of Rotating Magnetic Field on Susceptibility Profile of Methicillin-Resistant Staphylococcus aureus Strains Exposed to Activity of Different Groups of Antibiotics
Authors: Woroszyło Marta , Ciecholewska-Juśko Daria , Junka Adam , Wardach Marcin , Chodaczek Grzegorz , Dudek Bartłomiej , Fijałkowski Karol
Published: October 2021

Methicillin-resistant strains of Staphylococcus aureus (MRSA) have become a global issue for healthcare systems due to their resistance to most β-lactam antibiotics, frequently accompanied by resistance to other classes of antibiotics. In this work, we analyzed the impact of combined use of rotating magnetic field (RMF) with various classes of antibiotics (β-lactams, glycopeptides, macrolides, lincosamides, aminoglycosides, tetracyclines, and fluoroquinolones) against nine S. aureus strains (eight methicillin-resistant and one methicillin-sensitive). The results indicated that the application of RMF combined with antibiotics interfering with cell walls (particularly with the β-lactam antibiotics) translate into favorable changes in staphylococcal growth inhibition zones or in minimal inhibitory concentration values compared to the control settings, which were unexposed to RMF. As an example, the MIC value of cefoxitin was reduced in all MRSA strains by up to 42 times. Apart from the β-lactams, the reduced MIC values were also found for erythromycin, clindamycin, and tetracycline (three strains), ciprofloxacin (one strain), gentamicin (six strains), and teicoplanin (seven strains). The results obtained with the use of in vitro biofilm model confirm that the disturbances caused by RMF in the bacterial cell walls increase the effectiveness of the antibiotics towards MRSA. Because the clinical demand for new therapeutic options effective against MRSA is undisputable, the outcomes and conclusions drawn from the present study may be considered an important road into the application of magnetic fields to fight infections caused by methicillin-resistant staphylococci.
Pathophysiology and Molecular Imaging of Diabetic Foot Infections
Authors: Rubitschung Katie , Sherwood Amber , Crisologo Andrew P. , Bhavan Kavita , Haley Robert W. , Wukich Dane K. , Castellino Laila , Hwang Helena , La Fontaine Javier , Chhabra Avneesh , Lavery Lawrence , Öz Orhan K.
Published: October 2021

Diabetic foot infection is the leading cause of non-traumatic lower limb amputations worldwide. In addition, diabetes mellitus and sequela of the disease are increasing in prevalence. In 2017, 9.4% of Americans were diagnosed with diabetes mellitus (DM). The growing pervasiveness and financial implications of diabetic foot infection (DFI) indicate an acute need for improved clinical assessment and treatment. Complex pathophysiology and suboptimal specificity of current non-invasive imaging modalities have made diagnosis and treatment response challenging. Current anatomical and molecular clinical imaging strategies have mainly targeted the host’s immune responses rather than the unique metabolism of the invading microorganism. Advances in imaging have the potential to reduce the impact of these problems and improve the assessment of DFI, particularly in distinguishing infection of soft tissue alone from osteomyelitis (OM). This review presents a summary of the known pathophysiology of DFI, the molecular basis of current and emerging diagnostic imaging techniques, and the mechanistic links of these imaging techniques to the pathophysiology of diabetic foot infections.
From Blood to Regenerative Tissue: How Autologous Platelet-Rich Fibrin Can Be Combined with Other Materials to Ensure Controlled Drug and Growth Factor Release
Authors: Egle Karina , Salma Ilze , Dubnika Arita
Published: October 2021

The purpose of this review is to examine the latest literature on the use of autologous platelet-rich fibrin as a drug and growth factor carrier system in maxillofacial surgery. Autologous platelet-rich fibrin (PRF) is a unique system that combines properties such as biocompatibility and biodegradability, in addition to containing growth factors and peptides that provide tissue regeneration. This opens up new horizons for the use of all beneficial ingredients in the blood sample for biomedical purposes. By itself, PRF has an unstable effect on osteogenesis: therefore, advanced approaches, including the combination of PRF with materials or drugs, are of great interest in clinics. The main advantage of drug delivery systems is that by controlling drug release, high drug concentrations locally and fewer side effects within other tissue can be achieved. This is especially important in tissues with limited blood supply, such as bone tissue compared to soft tissue. The ability of PRF to degrade naturally is considered an advantage for its use as a “warehouse” of controlled drug release systems. We are focusing on this concentrate, as it is easy to use in manipulations and can be delivered directly to the surgical site. The target audience for this review are researchers and medical doctors who are involved in the development and research of PRFs further studies. Likewise, surgeons who use PRF in their work to treat patients and who advice patients to take the medicine orally.
Gellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair
Authors: Ramburrun Poornima , Kumar Pradeep , Ndobe Elias , Choonara Yahya E.
Published: October 2021

Optimal levels of functional recovery in peripheral nerve injuries remain elusive due to the architectural complexity of the neuronal environment. Commercial nerve repair conduits lack essential guidance cues for the regenerating axons. In this study, the regenerative potential of a biosimulated nerve repair system providing three types of regenerative cues was evaluated in a 10 mm sciatic nerve-gap model over 4 weeks. A thermo-ionically crosslinked gellan-xanthan hydrogel conduit loaded with electrospun PHBV-magnesium oleate-N-acetyl-cysteine (PHBV-MgOl-NAC) nanofibers was assessed for mechanical properties, nerve growth factor (NGF) release kinetics and PC12 viability. In vivo functional recovery was based on walking track analysis, gastrocnemius muscle mass and histological analysis. As an intraluminal filler, PHBV-MgOl-NAC nanofibers improved matrix resilience, deformation and fracture of the hydrogel conduit. NGF release was sustained over 4 weeks, governed by Fickian diffusion and Case-II relaxational release for the hollow conduit and the nanofiber-loaded conduit, respectively. The intraluminal fibers supported PC12 proliferation by 49% compared to the control, preserved up to 43% muscle mass and gradually improved functional recovery. The combined elements of physical guidance (nanofibrous scaffolding), chemical cues (N-acetyl-cysteine and magnesium oleate) and therapeutic cues (NGF and diclofenac sodium) offers a promising strategy for the regeneration of severed peripheral nerves.
Retinal Degeneration and Microglial Dynamics in Mature Progranulin-Deficient Mice
Authors: Takahashi Kei , Nakamura Shinsuke , Shimazawa Masamitsu , Hara Hideaki
Published: October 2021

Progranulin (PGRN) is a secreted glycoprotein that regulates numerous cellular processes. The role of PGRN as a regulator of lysosomes has recently received attention. The purpose of this study was to characterize the retinal phenotype in mature PGRN knockout (Grn−/−) mice. The a-wave amplitude of scotopic electroretinogram and outer nuclear thickness were significantly reduced at 6 months of age in Grn−/− mice compared to wild-type (Grn+/+) mice. In Grn−/− mice, retinal microglial cells accumulated on the retinal pigment epithelium (RPE) apical layer, and the number of infiltrated microglia and white fundus lesions between 2 and 6 months of age showed a close affinity. In Grn+/+ mice, PGRN was located in the retina, while the strongest PGRN signals were detected in the RPE-choroid. The different effects of PGRN deficiency on the expression of lysosomal proteins between the retina and RPE-choroid were demonstrated. Our data suggest that the subretinal translocation of microglia is a characteristic phenotype in the retina of mature PGRN knockout mice. The different effects of PGRN deficiency on the expression of lysosomal proteins between the retina and RPE-choroid might modulate microglial dynamics in PGRN knockout mice.
Semi-Automated High-Throughput Substrate Screening Assay for Nucleoside Kinases
Authors: Hellendahl Katja F. , Fehlau Maryke , Hans Sebastian , Neubauer Peter , Kurreck Anke
Published: October 2021

Nucleoside kinases (NKs) are key enzymes involved in the in vivo phosphorylation of nucleoside analogues used as drugs to treat cancer or viral infections. Having different specificities, the characterization of NKs is essential for drug design and nucleotide analogue production in an in vitro enzymatic process. Therefore, a fast and reliable substrate screening method for NKs is of great importance. Here, we report on the validation of a well-known luciferase-based assay for the detection of NK activity in a 96-well plate format. The assay was semi-automated using a liquid handling robot. Good linearity was demonstrated (r² > 0.98) in the range of 0–500 µM ATP, and it was shown that alternative phosphate donors like dATP or CTP were also accepted by the luciferase. The developed high-throughput assay revealed comparable results to HPLC analysis. The assay was exemplarily used for the comparison of the substrate spectra of four NKs using 20 (8 natural, 12 modified) substrates. The screening results correlated well with literature data, and additionally, previously unknown substrates were identified for three of the NKs studied. Our results demonstrate that the developed semi-automated high-throughput assay is suitable to identify best performing NKs for a wide range of substrates.
Clinical and Prognostic Value of Antigen-Presenting Cells with PD-L1/PD-L2 Expression in Ovarian Cancer Patients
Authors: Pawłowska Anna , Kwiatkowska Agnieszka , Suszczyk Dorota , Chudzik Agata , Tarkowski Rafał , Barczyński Bartłomiej , Kotarski Jan , Wertel Iwona
Published: October 2021

The latest literature demonstrates the predominant role of the programmed cell death axis (PD-1/PD-L1/PD-L2) in ovarian cancer (OC) pathogenesis. However, data concerning this issue is ambiguous. Our research aimed to evaluate the clinical importance of PD-L1/PD-L2 expression in OC environments. We evaluated the role of PD-L1/PD-L2 in OC patients (n = 53). The analysis was performed via flow cytometry on myeloid (mDCs) and plasmacytoid dendritic cells (pDCs) and monocytes/macrophages (MO/MA) in peripheral blood, peritoneal fluid (PF), and tumor tissue (TT). The data were correlated with clinicopathological characteristics and prognosis of OC patients. The concentration of soluble PD-L1 (sPD-L1) and PD-1 in the plasma and PF were determined by ELISA. We established an accumulation of PD-L1+/PD-L2+ mDCs, pDCs, and MA in the tumor microenvironment. We showed an elevated level of sPD-L1 in the PF of OC patients in comparison to plasma and healthy subjects. sPD-L1 levels in PF showed a positive relationship with Ca125 concentration. Moreover, we established an association between higher sPD-L1 levels in PF and shorter survival of OC patients. An accumulation of PD-L1+/PD-L2+ mDCs, pDCs, and MA in the TT and high sPD-L1 levels in PF could represent the hallmark of immune regulation in OC patients.
Deciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas
Authors: De Vita Alessandro , Vanni Silvia , Fausti Valentina , Cocchi Claudia , Recine Federica , Miserocchi Giacomo , Liverani Chiara , Spadazzi Chiara , Bassi Massimo , Gessaroli Manlio , Campobassi Angelo , De Luca Giovanni , Pieri Federica , Farnedi Anna , Franchini Eugenia , Ferrari Anna , Domizio Chiara , Cavagna Enrico , Gurrieri Lorena , Bongiovanni Alberto , Riva Nada , Calpona Sebastiano , Di Menna Giandomenico , Debonis Silvia Angela , Ibrahim Toni , Mercatali Laura
Published: October 2021

Adult rhabdomyosarcoma (RMS) represents an uncommon entity with an incidence of less than 3% of all soft tissue sarcomas (STS). Consequently, the natural history and the clinical management of this disease are infrequently reported. In order to fill this gap, we investigated the molecular biology of an adult RMS case series. The expression of epithelial mesenchymal transition-related gene and chemoresistance-related gene panels were evaluated. Moreover, taking advantage of our STS translational model combining patient-derived primary culture and 3D-scaffold, the pharmacological profile of an adult head and neck sclerosing RMS was assessed. Furthermore, NGS, microsatellite instability, and in silico analyses were carried out. RT-PCR identified the upregulation of CDH1, SLUG, MMP9, RAB22a, S100P, and LAPTM4b, representing promising biomarkers for this disease. Pharmacological profiling showed the highest sensitivity with anthracycline-based regimen in both 2D and 3D culture systems. NGS analysis detected RAB3IP-HMGA2 in frame gene rearrangement and FGFR4 mutation; microsatellite instability analysis did not detect any alteration. In silico analysis confirmed the mutation of FGFR4 as a promising marker for poor prognosis and a potential therapeutic target. We report for the first time the molecular and pharmacological characterization of rare entities of adult head and neck and posterior trunk RMS. These preliminary data could shed light on this poorly understood disease.
A Review of Calcineurin Biophysics with Implications for Cardiac Physiology
Authors: Williams Ryan B. , Johnson Christopher N.
Published: October 2021

Calcineurin, also known as protein phosphatase 2B, is a heterodimeric serine threonine phosphatase involved in numerous signaling pathways. During the past 50 years, calcineurin has been the subject of extensive investigation. Many of its cellular and physiological functions have been described, and the underlying biophysical mechanisms are the subject of active investigation. With the abundance of techniques and experimental designs utilized to study calcineurin and its numerous substrates, it is difficult to reconcile the available information. There have been a plethora of reports describing the role of calcineurin in cardiac disease. However, a physiological role of calcineurin in healthy cardiomyocyte function requires clarification. Here, we review the seminal biophysical and structural details that are responsible for the molecular function and inhibition of calcineurin. We then focus on literature describing the roles of calcineurin in cardiomyocyte physiology and disease.
Non-Coding RNAs as Regulators of Myogenesis and Postexercise Muscle Regeneration
Authors: Archacka Karolina , Ciemerych Maria A. , Florkowska Anita , Romanczuk Karolina
Published: October 2021

miRNAs and lncRNAs do not encode proteins, but they play an important role in the regulation of gene expression. They differ in length, biogenesis, and mode of action. In this work, we focus on the selected miRNAs and lncRNAs involved in the regulation of myogenesis and muscle regeneration. We present selected miRNAs and lncRNAs that have been shown to control myogenic differentiation and show that manipulation of their levels could be used to improve myogenic differentiation of various types of stem and progenitor cells. Finally, we discuss how physical activity affects miRNA and lncRNA expression and how it affects muscle well-being.
Ionising Radiation Promotes Invasive Potential of Breast Cancer Cells: The Role of Exosomes in the Process
Authors: AL-Abedi Raheem , Tuncay Cagatay Seda , Mayah Ammar , Brooks Susan A. , Kadhim Munira
Published: October 2021

Along with the cells that are exposed to radiation, non-irradiated cells can unveil radiation effects as a result of intercellular communication, which are collectively defined as radiation induced bystander effects (RIBE). Exosome-mediated signalling is one of the core mechanisms responsible for multidirectional communication of tumor cells and their associated microenvironment, which may result in enhancement of malignant tumor phenotypes. Recent studies show that exosomes and exosome-mediated signalling also play a dynamic role in RIBE in cancer cell lines, many of which focused on altered exosome cargo or their effects on DNA damage. However, there is a lack of knowledge regarding how these changes in exosome cargo are reflected in other functional characteristics of cancer cells from the aspects of invasiveness and metastasis. Therefore, in the current study, we aimed to investigate exosome-mediated bystander effects of 2 Gy X-ray therapeutic dose of ionizing radiation on the invasive potential of MCF-7 breast cancer cells in vitro via assessing Matrigel invasion potential, epithelial mesenchymal transition (EMT) characteristics and the extent of glycosylation, as well as underlying plausible molecular mechanisms. The findings show that exosomes derived from irradiated MCF-7 cells enhance invasiveness of bystander MCF-7 cells, possibly through altered miRNA and protein content carried in exosomes.
Rho/ROCK Pathway and Noncoding RNAs: Implications in Ischemic Stroke and Spinal Cord Injury
Authors: Kimura Tetsu , Horikoshi Yuta , Kuriyagawa Chika , Niiyama Yukitoshi
Published: October 2021

Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability. RhoA is a small GTPase protein that activates a downstream effector, ROCK. The up-regulation of the RhoA/ROCK pathway contributes to neuronal apoptosis, neuroinflammation, blood-brain barrier dysfunction, astrogliosis, and axon growth inhibition in IS and SCI. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), were previously considered to be non-functional. However, they have attracted much attention because they play an essential role in regulating gene expression in physiological and pathological conditions. There is growing evidence that ROCK inhibitors, such as fasudil and VX-210, can reduce injury in IS and SCI in animal models and clinical trials. Recently, it has been reported that miRNAs are decreased in IS and SCI, while lncRNAs are increased. Inhibiting the Rho/ROCK pathway with miRNAs alleviates apoptosis, neuroinflammation, oxidative stress, and axon growth inhibition in IS and SCI. Further studies are required to explore the significance of ncRNAs in IS and SCI and to establish new strategies for preventing and treating these devastating diseases.
Short-Term Outcomes of Colorectal Stenting Using a Low Axial Force Self-Expandable Metal Stent for Malignant Colorectal Obstruction: A Japanese Multicenter Prospective Study
Authors: Sasaki Takashi , Yoshida Shuntaro , Isayama Hiroyuki , Narita Akiko , Yamada Tomonori , Enomoto Toshiyuki , Sumida Yorinobu , Kyo Rika , Kuwai Toshio , Tomita Masafumi , Moroi Rintaro , Shimada Mamoru , Hirata Nobuto , Saida Yoshihisa
Published: October 2021

(1) Background: Endoscopic colorectal stenting with high technical success and safety is essential in discussing the oncological outcomes for the management of malignant colorectal obstruction. Mechanical properties of self-expandable metal stents are usually considered to affect clinical outcomes. (2) Methods: A multicenter, prospective study was conducted in Japan. A self-expandable metal stent with low axial force was inserted endoscopically. The primary endpoint was clinical success, defined as the resolution of symptoms and radiological findings within 24 h. Secondary endpoints were technical success and adverse events. Short-term outcomes of 7 days were evaluated in this study. (3) Results: Two hundred and five consecutive patients were enrolled. Three patients were excluded, and the remaining 202 patients were evaluated. The technical and clinical success rates were 97.5% and 96.0%, respectively. Major stent-related adverse events included stent migration (1.0%), insufficient stent expansion (0.5%), and stent occlusion (0.5%). No colonic perforation was observed. There were two fatal cases (1%) which were not related to stent placement. (4) Conclusions: The placement of self-expandable metal stents with low axial force is safe with no perforation and showed high technical and clinical success rates in short-term outcomes for the management of malignant colorectal obstruction.
Comparison of Simultaneous Single-Position Oblique Lumbar Interbody Fusion and Percutaneous Pedicle Screw Fixation with Posterior Lumbar Interbody Fusion Using O-arm Navigated Technique for Lumbar Degenerative Diseases
Authors: Tan Ying , Tanaka Masato , Sonawane Sumeet , Uotani Koji , Oda Yoshiaki , Fujiwara Yoshihiro , Arataki Shinya , Yamauchi Taro , Takigawa Tomoyuki , Ito Yasuo
Published: October 2021

Minimally invasive posterior or transforaminal lumbar interbody fusion (MI-PLIF/TLIF) are widely accepted procedures for lumbar instability due to degenerative or traumatic diseases. Oblique lateral interbody fusion (OLIF) is currently receiving considerable attention because of the reductions in damage to the back muscles and neural tissue. The aim of this study was to compare clinical and radiographic outcomes of simultaneous single-position OLIF and percutaneous pedicle screw (PPS) fixation with MI-PLIF/TLIF. This retrospective comparative study included 98 patients, comprising 63 patients with single-position OLIF (Group SO) and 35 patients with MI-PLIF/TLIF (Group P/T). Cases with more than 1 year of follow-up were included in this study. Mean follow-up was 32.9 ± 7.0 months for Group SO and 33.7 ± 7.5 months for Group P/T. Clinical and radiological evaluations were performed. Comparing Group SO to Group P/T, surgical time and blood loss were 118 versus 172 min (p < 0.01) and 139 versus 374 mL (p < 0.01), respectively. Cage height, change in disk height, and postoperative foraminal height were significantly higher in Group SO than in Group P/T. The fusion rate was 96.8% in Group SO, similar to the 94.2% in Group P/T (p = 0.985). The complication rate was 6.3% in Group SO and 14.1% in Group P/T (p = 0.191). Simultaneous single position O-arm-navigated OLIF reduces the surgical time, blood loss, and time to ambulation after surgery. Good indirect decompression can be achieved with this method.
The Broken Heart: The Role of Life Events in Takotsubo Syndrome
Authors: Casagrande Maria , Forte Giuseppe , Favieri Francesca , Agostini Francesca , Giovannoli Jasmine , Arcari Luca , Passaseo Ilaria , Semeraro Raffaella , Camastra Giovanni , Langher Viviana , Pazzaglia Mariella , Cacciotti Luca
Published: October 2021

The onset of Takotsubo syndrome (TTS), also known as stress cardiomyopathy, is thought to be associated with some life events. This study focuses on clarifying life event characteristics and the role of triggers in the onset of TTS. Participants with TTS (n = 54) were compared to those with acute myocardial infarction (AMI; n = 52) and healthy individuals (n = 54). Using a modified version of the Interview for Recent Life Events, information about general life events perceived as stressful and triggers preceding the onset of a cardiac syndrome was collected. The assessment included the impact of these events as indicated by the participants and estimated by the interviewer; finally, the objective impact was considered. Although the number of events and the objective impact did not differ among the groups, patients with TTS reported a more negative perceived impact. Moreover, 61% of these patients objectively and subjectively reported a more stressful trigger before the onset of the disease (in the 24 h preceding the cardiac event) than those reported by patients with AMI. The dynamic between life events and individual responses could help differentiate TTS from other cardiovascular events, such as AMI. This study suggests that patients’ perception of some life events (whether triggers or general life events) could represent a possible marker of TTS.
Off-Label Use of Rituximab in Patients with Different Types of Nephropathies in a Tertiary Hospital: A Retrospective Study
Authors: Sans-Pola Carla , Agustí Antònia , Bosch Josep Àngel , Agraz Irene , Alerany Carmen , Danés Immaculada
Published: October 2021

Off-label use of rituximab is commonly requested for patients with resistant nephropathies. The outcomes and tolerability of rituximab in adult patients with nephropathy treated at our hospital (from 2013 to 2018) were described. Data were retrieved from electronic medical records. Response was classified as complete remission (CR), partial remission (PR), or no response (NR) according to the KDIGO criteria. A total of 89 requests were received for 61 patients. Median age was 58 years (45.9% female). Idiopathic membranous nephropathy (MN) (n = 30) was the most frequent indication, followed by minimal change disease (MCD) (n = 15) and secondary membranoproliferative glomerulonephritis (MPGN) (n = 12). Three patients with focal segmental glomerulosclerosis (FSGS) were included. After most treatment cycles in MN, a CR or PR was observed; median proteinuria levels significantly decreased for these patients (6000 mg/24h (IQR 3584–10,300) vs. 1468.8 (IQR 500–4604.25), p < 0.01). In MPGN, no response was documented after 46.7% of rituximab cycles. A CR or PR was described with the majority of rituximab cycles in MCD, with a significant decrease in proteinuria (6000 mg/24 h (IQR 4007–11,426) vs. 196.8 (IQR 100–1300), p = 0.013). No cycles produced a response in FSGS. Mean CD19+ B-cell decreased in all types of nephropathy (10.44% vs. 0.29%, p < 0.0001). Eleven patients presented infusion-related reactions, and 17 presented infectious complications. The majority of patients with MN and MCD had complete or partial responses; however, neither MPGN nor FSGS had encouraging results.
How Should Patients with a Thoracolumbar Injury Classification and Severity Score of 4 Be Treated?
Authors: Lee Nam-Hun , Kim Sung-Kyu , Seo Hyoung-Yeon , Park Eric T. , Jang Won-Young
Published: October 2021

The thoracolumbar injury classification and severity score (TLICS) system help surgeons decide whether patients should undergo initial operative treatment or nonoperative treatment. However, the best treatment for patients with TLICS 4 fracture remains unknown. The aim of this study was to identify the risk factors for nonoperative treatment failure in patients with TLICS 4 fracture and establish treatment standards for TLICS 4 fractures. This study included 44 patients with TLICS 4 fracture who initially received nonoperative treatment. We divided these patients into two groups: the successful nonoperative treatment group included 18 patients, and the operative treatment group after nonoperative treatment failure included 26 patients. In multiple logistic regression analysis, spinal canal compromise (odd ratio = 1.316) and kyphotic angle (odd ratio = 1.416) were associated with nonoperative treatment failure in patients with TLICS 4 fracture. Other factors, including age, sex, BMI, initial VAS score, and loss of vertebral body height, were not significantly associated with nonoperative treatment failure in these patients. Spinal canal compromise and kyphotic angle were associated with nonoperative treatment failure in patients with TLICS 4 fracture. Therefore, we recommend the surgeon observe spinal canal compromise and kyphotic angle more carefully when deciding on the treatment of patients with TLICS 4 fracture.
The Role of Hemoglobin A1C in Diabetes Screening and Diabetic Retinopathy
Authors: Chang Villacreses Maria Mercedes , Karnchanasorn Rudruidee , Ou Horng-Yih , Samoa Raynald , Chuang Lee-Ming , Chiu Ken C.
Published: October 2021

Hemoglobin A1C (A1C) is used in various settings. Its performance has not been evaluated systemically. We compared A1C in diagnosis of diabetes with fasting plasma glucose (FPG) and 2-h postchallenged plasma glucose (2hPG) parameters in a cross-sectional cohort in the United Stated. Adult subjects (≥20 years) were identified from the National Health and Nutrition Examination Survey 2005–2016 without a history of diabetes who had BMI, A1C, FPG, and 2hPG (n = 10,416). For comparisons, we calculated the sample weighted prevalence, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with subgroup analyses. For the retinopathy study, diabetic subjects with established diabetes who responded to the question of diabetic retinopathy were evaluated (n = 3907). Compared to the FPG/2hPG criteria, A1C ≥ 48 mmol/mol (6.5%) had a low sensitivity at 25.90%, with specificity 99.70%, PPV 84.70%, and NPV 95.70%. Subgroup analyses revealed a lower sensitivity in males (24.52%); the lowest in non-Hispanic White (21.35%), in the third decade (14.32%), and in the BMI < 22.50 kg/m2 group (7.21%). The prevalence of self-reported diabetic retinopathy increased drastically with an inflection point at A1C 48 mmol/mol (6.5%) from 11.52% to 18.32% (p < 0.0001). A1C ≥ 48 mmol/mol (6.5%) should be cautiously used to diagnose diabetes in certain subgroups due to very low sensitivity in certain groups. With the confirmation of the association of increasing self-reported diabetic retinopathy with A1C ≥ 48 mmol/mol (6.5%), the current A1C cutoff is an acceptable value with the understanding of especially low sensitivity in certain subgroups.
The Effects of Sex and Body Weight on Renal Graft Function—The Role of CCL2
Authors: Nalewajska Magdalena , Opara-Bajerowicz Martyna , Safranow Krzysztof , Pawlik Andrzej , Ciechanowski Kazimierz , Kwiatkowski Sebastian , Kwiatkowska Ewa
Published: October 2021

There are reports on the effects of excessive recipient body weight on renal graft function. Increased CCL2 (chemokine CC-mortif ligand 2) production is observed in patients with excessive body weight. CCL2 also exacerbates the inflammatory process in the renal graft. A total of 49 renal graft recipients of both sexes having undergone renal biopsy within the last 18 months were retrospectively reviewed. At their most recent appointment the patients’ plasma concentrations of CCL2 were evaluated. Renal function was assessed retrospectively. CCL2 concentrations were higher in men than women (p < 0.047), while higher CCL2 levels were associated with a decrease in eGFR (estimated glomerular filtration rate) during the first year post Tx (kidney transplantation). CCL2 negatively correlated with eGFR at 5 years (R = −0.45, p < 0.040997) and positively correlated with the degree of tubular atrophy in renal biopsy specimens (R = 0.43, p < 0.027293) and with systolic pressure. Men showed significantly higher BMI (body mass index) values at the time of Tx and at their last appointment than women did (p < 0.000403; p < 0.000613, respectively). Men showed poorer long-term renal graft function, with significantly lower eGFR values at 4 and 5 years into the post-transplantation period. The male sex and excessive body weight have adverse effects on short- and long-term renal graft function, which is associated with increased levels of CCL2.
Automatic Continuous Control of Cuff Pressure and Subglottic Secretion Suction Used Together to Prevent Pneumonia in Ventilated Patients—A Retrospective and Prospective Cohort Study
Authors: Tomaszek Lucyna , Pawlik Jarosław , Mazurek Henryk , Mędrzycka-Dąbrowska Wioletta
Published: October 2021

The ventilator bundle consists of multiple methods to reduce ventilator-associated pneumonia (VAP) rates in Intensive Care Units (ICU). The aim of the study was to evaluate how the continuous automatic pressure control in tapered cuffs of endotracheal/tracheostomy tubes applied along with continuous automatic subglottic secretion suction affect the incidence of VAP. In the prospective cohort (n = 198), the standard VAP bundle was modified by continuous automatic pressure control in taper-shaped cuff of endotracheal/tracheostomy tubes and subglottic secretion suction. VAP incidence, time to VAP onset, invasive mechanical ventilation days/free days, length of ICU stay, ICU mortality, and multidrug-resistant bacteria were assessed and compared to the retrospective cohort (n = 173) with the standard bundle (intermittent cuff pressure of standard cuff, lack of subglottic secretion suction). A smaller incidence of VAP (9.6% vs. 19.1%) and early onset VAP (1.5% vs. 8.1%) was found in the prospective compared to the retrospective cohort (p < 0.01). Patients in the prospective cohort were less likely to develop VAP (RR = 0.50; 95% CI: 0.29 to 0.85) and early-onset VAP (RR = 0.19; 95% CI: 0.05 to 0.64) and had longer time to onset VAP (median 9 vs. 5 days; p = 0.03). There was no significant difference (p > 0.05) between both cohorts in terms of invasive mechanical ventilation days/free days, length of ICU stay, ICU mortality and multidrug-resistant bacteria. Modification of the bundle for prevention of VAP can reduce early-onset VAP and total incidence of VAP and delay the time of VAP occurrence.
Mechanical Ventilation during Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome: A Narrative Review
Authors: Chiu Li-Chung , Kao Kuo-Chin
Published: October 2021

Acute respiratory distress syndrome (ARDS) is a life-threatening condition involving acute hypoxemic respiratory failure. Mechanical ventilation remains the cornerstone of management for ARDS; however, potentially injurious mechanical forces introduce the risk of ventilator-induced lung injury, multiple organ failure, and death. Extracorporeal membrane oxygenation (ECMO) is a salvage therapy aimed at ensuring adequate gas exchange for patients suffering from severe ARDS with profound hypoxemia where conventional mechanical ventilation has failed. ECMO allows for lower tidal volumes and airway pressures, which can reduce the risk of further lung injury, and allow the lungs to rest. However, the collateral effect of ECMO should be considered. Recent studies have reported correlations between mechanical ventilator settings during ECMO and mortality. In many cases, mechanical ventilation settings should be tailored to the individual; however, researchers have yet to establish optimal ventilator settings or determine the degree to which ventilation load can be decreased. This paper presents an overview of previous studies and clinical trials pertaining to the management of mechanical ventilation during ECMO for patients with severe ARDS, with a focus on clinical findings, suggestions, protocols, guidelines, and expert opinions. We also identified a number of issues that have yet to be adequately addressed.
The Association of Cardiometabolic Disease with Psychological Factors in Colombian People during the COVID-19 Pandemic: A Cross-Sectional Study
Authors: García-Garro Patricia Alexandra , Aibar-Almazán Agustín , Rivas-Campo Yulieth , Vega-Ávila Gloria Cecilia , Afanador-Restrepo Diego Fernando , Martínez-Amat Antonio , Afanador-Rodríguez María Isabel , Castellote-Caballero Yolanda , Hita-Contreras Fidel
Published: October 2021

During the COVID-19 pandemic, psychological disorders have been documented in the population, and their exacerbation in vulnerable populations such as those with Cardiometabolic Diseases (CD) might challenge health systems. This study determined psychological factors associated with CD in Colombian adults during the COVID-19 pandemic. For this purpose, 284 persons were evaluated, 142 without CD and 142 with CD. Sociodemographic data were collected, and the International Physical Activity Questionnaire (IPAQ), the SF-12v2, the Pittsburgh Sleep Quality Index (PSQI) and the Zung Self-Rating Depression Scale (ZSDS), which were integrated into an online form, were used. Through a simple and multiple logistic regression model, it was shown that CD was associated with low sleeping quality (LSQ) (OR = 3.51) and with depressive symptoms (DS) (OR = 1.98). In addition, in the group with CD, the presence of DS was related to BMI (OR = 2.45), and LSQ was related to living with persons at risk for COVID-19 (OR = 3.64) and BMI (OR = 5.88). In conclusion, this study showed that people with CD have a higher chance of presenting DS and LSQ. Furthermore, living with people at risk for COVID-19 was related to the presence of LSQ.
Comparison of Ultrasound Descriptors of Abnormally Invasive Placenta (AIP) over the Course of the Second and Third Trimester—Is an Increase Verifiable?
Authors: Gorczyca Monika E. , Springer Stephanie , Pateisky Petra , Ott Johannes , Ulm Barbara , Chalubinski Kinga
Published: October 2021

Limited data exist regarding the course of abnormally invasive placentation (AIP) (=placenta accreta spectrum (PAS)) during the 2nd and 3rd trimester, although this knowledge would be important for optimal patient care. In this retrospective single-center longitudinal cohort study, potential aggravation of AIP was evaluated in 37 patients with ultrasound (US) pictures stored on a minimum of two visits. Five raters, blinded to diagnosis and gestational age, judged the degree of AIP as recommended by the International Society for PAS. The probability of invasiveness was estimated as absent, low, intermediate, severe (0–3 points), the extent as absent, focal, diffuse (0–2 points), and the presence and appearance of each US-sign as absent, mild, severe (0–3 points). None of the 10 judged signs appeared more severe (p ≥ 0.41) with progressing pregnancy. Neither the number of positively scored US-signs (earlier scan; 6.14 ± 2.06, later scan; 5.94 ± 2.16; p = 0.28), nor the estimated probability & extent of AIP rose (3.69 ± 1.15 vs. 3.67 ± 1.22; p = 1.0). Test-retest reliability corroborated excellent agreement between visits (mean number of positive US-signs ICC (3,1) = 0.94, 95% CI 0.91–0.97; p < 0.0001). Overall, there was no clinically detectable increase in invasiveness over the course of the 2nd and 3rd trimester. This should be further evaluated in prospective studies.
Efficacy of a Preparation Based on Calcium Butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and Fructooligosaccharides in the Prevention of Relapse in Ulcerative Colitis: A Prospective Observational Study
Authors: Caviglia Gian Paolo , De Blasio Federico , Vernero Marta , Armandi Angelo , Rosso Chiara , Saracco Giorgio Maria , Bugianesi Elisabetta , Astegiano Marco , Ribaldone Davide Giuseppe
Published: October 2021

Several compounds based on short chain fatty acids and/or probiotics/prebiotics have shown promising results in the therapy of ulcerative colitis (UC), possibly due to its key role in restoring gut homeostasis as well as intestinal barrier integrity. Here, we investigated the efficacy of a patented preparation based on calcium butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and fructooligosaccharides (FEEDColon®, Princeps, Cuneo, Italy) in maintaining remission and improving subjective symptoms and inflammatory indices in patients with UC receiving 5-ASA therapy. A total of 42 patients were prospectively recruited and randomized in 21 patients receiving combination therapy with mesalamine (5-ASA) plus FEEDColon® and 21 patients treated with standard 5-ASA therapy. Patients were assessed at baseline, at 6-month, and 12-month follow-up (FU). Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12-month FU) was reached by 32 (76%) patients: 20 (95%) among those treated with 5-ASA + FeedColon®, and 12 (57%) among those treated with 5-ASA only (p = 0.009). Consistently, patients treated with combination therapy improved subjective symptoms (quality of life, abdominal pain, and stool consistency) and reduced FC values, while those treated with 5-ASA alone, improved neither subjective symptoms nor FC during the FU. In conclusion, FEEDColon® supplementation appears to be a valid add-on therapy for the maintenance of remission in patients with UC. Further multicentre, placebo-controlled, double-blind clinical trials are needed to validate our results on larger cohorts of patients with UC.