bluuebunny/crossref_metadata_2025 huggingface dataset:
Is There Enough Evidence to Support the Role of Glycosaminoglycans and Proteoglycans in Thoracic Aortic Aneurysm and Dissection?—A Systematic Review
Authors: Rai Pratik , Robinson Lucy , Davies Hannah A. , Akhtar Riaz , Field Mark , Madine Jillian
Published: August 2022

Altered proteoglycan (PG) and glycosaminoglycan (GAG) distribution within the aortic wall has been implicated in thoracic aortic aneurysm and dissection (TAAD). This review was conducted to identify literature reporting the presence, distribution and role of PGs and GAGs in the normal aorta and differences associated with sporadic TAAD to address the question; is there enough evidence to establish the role of GAGs/PGs in TAAD? 75 studies were included, divided into normal aorta (n = 51) and TAAD (n = 24). There is contradictory data regarding changes in GAGs upon ageing; most studies reported an increase in GAG sub-types, often followed by a decrease upon further ageing. Fourteen studies reported changes in PG/GAG or associated degradation enzyme levels in TAAD, with most increased in disease tissue or serum. We conclude that despite being present at relatively low abundance in the aortic wall, PGs and GAGs play an important role in extracellular matrix maintenance, with differences observed upon ageing and in association with TAAD. However, there is currently insufficient information to establish a cause-effect relationship with an underlying mechanistic understanding of these changes requiring further investigation. Increased PG presence in serum associated with aortic disease highlights the future potential of these biomolecules as diagnostic or prognostic biomarkers.
Rapid Synergistic Biofilm Production of Pseudomonas and Candida on the Pulmonary Cell Surface and in Mice, a Possible Cause of Chronic Mixed Organismal Lung Lesions
Authors: Phuengmaung Pornpimol , Mekjaroen Jiradej , Saisorn Wilasinee , Chatsuwan Tanittha , Somparn Poorichaya , Leelahavanichkul Asada
Published: August 2022

Due to the possible co-presence of Pseudomonas aeruginosa and Candida albicans (the most common nosocomial pathogens) in lungs, rapid interkingdom biofilm production is possible. As such, PA+CA produced more dominant biofilms on the pulmonary epithelial surface (NCI-H292) (confocal fluorescent extracellular matrix staining) with dominant psl upregulation, as demonstrated by polymerase chain reaction (PCR), after 8 h of experiments than PA alone. With a proteomic analysis, rhamnosyltransferase RhlB protein (Psl-associated quorum-sensing protein) was found to be among the high-abundance proteins in PA+CA than in PA biofilms, supporting psl-mediated biofilms in PA+CA on the cell surface. Additionally, PA+CA increased supernatant cytokines (IL-8 and IL-13, but not TNF-α, IL-6, and IL-10) with a similar upregulation of TLR-4, TLR-5, and TLR-9 (by PCR) compared with PA-stimulated cells. The intratracheal administration of PA+CA induced a greater severity of sepsis (serum creatinine, alanine transaminase, serum cytokines, and histology score) and prominent biofilms (fluorescent staining) with psl upregulation (PCR). In comparison with PA+CA biofilms on glass slides, PA+CA biofilms on biotic surfaces were more prominent (fluorescent staining). In conclusion, PA+CA induced Psl-predominant biofilms on the pulmonary cell surface and in mice with acute pneumonia, and these biofilms were more prominent than those induced by PA alone, highlighting the impact of Candida on rapid interkingdom biofilm production.
Fighting Antibiotic-Resistant Bacterial Infections by Surface Biofunctionalization of 3D-Printed Porous Titanium Implants with Reduced Graphene Oxide and Silver Nanoparticles
Authors: San Hongshan , Paresoglou Marianne , Minneboo Michelle , van Hengel Ingmar A. J. , Yilmaz Aytac , Gonzalez-Garcia Yaiza , Fluit Ad C. , Hagedoorn Peter-Leon , Fratila-Apachitei Lidy E. , Apachitei Iulian , Zadpoor Amir A.
Published: August 2022

Nanoparticles (NPs) have high multifunctional potential to simultaneously enhance implant osseointegration and prevent infections caused by antibiotic-resistant bacteria. Here, we present the first report on using plasma electrolytic oxidation (PEO) to incorporate different combinations of reduced graphene oxide (rGO) and silver (Ag) NPs on additively manufactured geometrically ordered volume-porous titanium implants. The rGO nanosheets were mainly embedded parallel with the PEO surfaces. However, the formation of ‘nano-knife’ structures (particles embedded perpendicularly to the implant surfaces) was also found around the pores of the PEO layers. Enhanced in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus was observed for the rGO+Ag-containing surfaces compared to the PEO surfaces prepared only with AgNPs. This was caused by a significant improvement in the generation of reactive oxygen species, higher levels of Ag+ release, and the presence of rGO ‘nano-knife’ structures. In addition, the implants developed in this study stimulated the metabolic activity and osteogenic differentiation of MC3T3-E1 preosteoblast cells compared to the PEO surfaces without nanoparticles. Therefore, the PEO titanium surfaces incorporating controlled levels of rGO+Ag nanoparticles have high clinical potential as multifunctional surfaces for 3D-printed orthopaedic implants.
Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis
Authors: Nishi Kensuke , Yoshimoto Shohei , Nishi Soichiro , Nishi Tatsuro , Nishi Ryushiro , Tanaka Takayuki , Tsunoda Toshiyuki , Imai Kazuaki , Tanaka Hiroaki , Hotta Osamu , Tanaka Ayaki , Hiromatsu Kenji , Shirasawa Senji , Nakagawa Takashi , Yamano Takafumi
Published: August 2022

The epipharynx, located behind the nasal cavity, is responsible for upper respiratory tract immunity; however, it is also the site of frequent acute and chronic inflammation. Previous reports have suggested that chronic epipharyngitis is involved not only in local symptoms such as cough and postnasal drip, but also in systemic inflammatory diseases such as IgA nephropathy and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Epipharyngeal Abrasive Therapy (EAT), which is an effective treatment for chronic epipharyngitis in Japan, is reported to be effective for these intractable diseases. The sedation of chronic epipharyngitis by EAT induces suppression of the inflammatory cytokines and improves systemic symptoms, which is considered to be one of the mechanisms, but there is no report that has proved this hypothesis. The purpose of this study was to clarify the anti-inflammatory effect of EAT histologically. The study subjects were 8 patients who were not treated with EAT and 11 patients who were treated with EAT for chronic epipharyngitis for 1 month or more. For immunohistochemical assessment, the expression pattern of IL-6 mRNA, which plays a central role in the human cytokine network, was analyzed using in situ hybridization. The expression of IL-6 in the EAT-treated group was significantly lower than those in the EAT nontreated group (p = 0.0015). In addition, EAT suppressed the expression of tumor necrosis factor alpha (TNFα), a crucial proinflammatory cytokine. As a result, continuous EAT suppressed submucosal cell aggregation and reduced inflammatory cytokines. Thus, EAT may contribute to the improvement of systemic inflammatory diseases through the suppression of IL-6 expression.
A Unique Enhancement of Propionibacterium freudenreichii’s Ability to Remove Pb(II) from Aqueous Solution by Tween 80 Treatment
Authors: George Fanny , Titécat Marie , Barois Nicolas , Daniel Catherine , Garat Anne , Jan Gwénaël , Foligné Benoît
Published: August 2022

Microbial agents have promise for the bioremediation of Pb(II)-polluted environments and wastewater, the biodecontamination of foods, and the alleviation of toxicity in living organisms. The dairy bacterium Propionibacterium freudenreichii is poorly able to remove Pb(II) from aqueous solution at 25 ppm, ranging from 0 to 10% of initial concentration. Here, we report on an original strong enhancement of this activity (ranging from 75% to 93%, p < 0.01) following the addition of a polysorbate detergent (Tween® 80) during or either shortly after the growth of a P. freudenreichii culture. We evaluated the optimal Tween® 80 concentration for pretreatment conditions, documented the role of other detergents, and explored the possible mechanisms involved. Our results reveal a novel, environmentally friendly, low-cost pretreatment procedure for enhancing the selective removal of lead from water by probiotic-documented bacteria.
Effects of G-Quadruplex-Binding Plant Secondary Metabolites on c-MYC Expression
Authors: Zenkov Roman G. , Kirsanov Kirill I. , Ogloblina Anna M. , Vlasova Olga A. , Naberezhnov Denis S. , Karpechenko Natalia Y. , Fetisov Timur I. , Lesovaya Ekaterina A. , Belitsky Gennady A. , Dolinnaya Nina G. , Yakubovskaya Marianna G.
Published: August 2022

Guanine-rich DNA sequences tending to adopt noncanonical G-quadruplex (G4) structures are over-represented in promoter regions of oncogenes. Ligands recognizing G4 were shown to stabilize these DNA structures and drive their formation regulating expression of corresponding genes. We studied the interaction of several plant secondary metabolites (PSMs) with G4s and their effects on gene expression in a cellular context. The binding of PSMs with G4s formed by the sequences of well-studied oncogene promoters and telomeric repeats was evaluated using a fluorescent indicator displacement assay. c-MYC G4 folding topology and thermal stability, as well as the PMS influence on these parameters, were demonstrated by UV-spectroscopy and circular dichroism. The effects of promising PSMs on c-MYC expression were assessed using luciferase reporter assay and qPR-PCR in cancer and immortalized cultured cells. The ability of PMS to multi-targeting cell signaling pathways was analyzed by the pathway-focused gene expression profiling with qRT-PCR. The multi-target activity of a number of PSMs was demonstrated by their interaction with a set of G4s mimicking those formed in the human genome. We have shown a direct G4-mediated down regulation of c-MYC expression by sanguinarine, quercetin, kaempferol, and thymoquinone; these effects being modulated by PSM’s indirect influence via cell signaling pathways.
Human Pluripotent Stem Cell-Derived Alveolar Organoid with Macrophages
Authors: Seo Ha-Rim , Han Hyeong-Jun , Lee Youngsun , Noh Young-Woock , Cho Seung-Ju , Kim Jung-Hyun
Published: August 2022

Alveolar organoids (AOs), derived from human pluripotent stem cells (hPSCs) exhibit lung-specific functions. Therefore, the application of AOs in pulmonary disease modeling is a promising tool for understanding disease pathogenesis. However, the lack of immune cells in organoids limits the use of human AOs as models of inflammatory diseases. In this study, we generated AOs containing a functional macrophage derived from hPSCs based on human fetal lung development using biomimetic strategies. We optimized culture conditions to maintain the iMACs (induced hPSC-derived macrophages) AOs for up to 14 days. In lipopolysaccharide (LPS)-induced inflammatory conditions, IL-1β, MCP-1 and TNF-α levels were significantly increased in iMAC-AOs, which were not detected in AOs. In addition, chemotactic factor IL-8, which is produced by mononuclear phagocytic cells, was induced by LPS treatment in iMACs-AOs. iMACs-AOs can be used to understand pulmonary infectious diseases and is a useful tool in identifying the mechanism of action of therapeutic drugs in humans. Our study highlights the importance of immune cell presentation in AOs for modeling inflammatory pulmonary diseases.
Red-Emissive Sulfur-Doped Carbon Dots for Selective and Sensitive Detection of Mercury (II) Ion and Glutathione
Authors: Zeng Jinjin , Liao Linhong , Lin Xiao , Liu Genyan , Luo Xiaogang , Luo Ming , Wu Fengshou
Published: August 2022

Carbon dots (CDs) show great potential in bioimaging and biosensing because of their good biocompatibility and excellent optical properties. However, CDs with intense red emissions for sensitive and selective detection are rarely reported. Herein, we prepared the red-emissive carbon dots (RCDs) through a facile hydrothermal method using tetra (4-carboxyphenyl) porphyrin (TCPP) and thiourea as starting materials. The obtained RCDs were characterized by TEM, XRD, and XPS. RCDs exhibited high water solubility and strong red emission (λem = 650 nm), with the fluorescence quantum yield as high as 26.7%, which was greatly higher than that of TCPP. Moreover, the as-prepared RCDs could be acted as a highly selective and sensitive probe for the detection of Hg2+ and glutathione (GSH) through the fluorometric titration method. The detection limits of Hg2+ and GSH were calculated to be 1.73 and 1.6 nM, respectively. The cellular experiments demonstrated the good biocompatibility of RCDs and their feasibility in bioimaging. Thus, this work provided a simple strategy to design and synthesize the highly red-emissive carbon dots, which showed promising application in biological and environmental assays.
Targeting ABCC6 in Mesenchymal Stem Cells: Impairment of Mature Adipocyte Lipid Homeostasis
Authors: Plümers Ricarda , Osterhage Michel R. , Lindenkamp Christopher , Knabbe Cornelius , Hendig Doris
Published: August 2022

Mutations in ABCC6, an ATP-binding cassette transporter with a so far unknown substrate mainly expressed in the liver and kidney, cause pseudoxanthoma elasticum (PXE). Symptoms of PXE in patients originate from the calcification of elastic fibers in the skin, eye, and vessels. Previous studies suggested an involvement of ABCC6 in cholesterol and lipid homeostasis. The intention of this study was to examine the influence of ABCC6 deficiency during adipogenic differentiation of human bone marrow-derived stem cells (hMSCs). Induction of adipogenic differentiation goes along with significantly elevated ABCC6 gene expression in mature adipocytes. We generated an ABCC6-deficient cell culture model using clustered regulatory interspaced short palindromic repeat Cas9 (CRISPR–Cas9) system to clarify the role of ABCC6 in lipid homeostasis. The lack of ABCC6 in hMSCs does not influence gene expression of differentiation markers in adipogenesis but results in a decreased triglyceride content in cell culture medium. Protein and gene expression analysis of mature ABCC6-deficient adipocytes showed diminished intra- and extra-cellular lipolysis, release of lipids, and fatty acid neogenesis. Therefore, our results demonstrate impaired lipid trafficking in adipocytes due to ABCC6 deficiency, highlighting adipose tissue and peripheral lipid metabolism as a relevant target for uncovering systemic PXE pathogenesis.
Phylogeography of Sub-Saharan Mitochondrial Lineages Outside Africa Highlights the Roles of the Holocene Climate Changes and the Atlantic Slave Trade
Authors: Sá Luísa , Almeida Mafalda , Azonbakin Simon , Matos Erica , Franco-Duarte Ricardo , Gómez-Carballa Alberto , Salas Antonio , Laleye Anatóle , Rosa Alexandra , Brehm António , Richards Martin B. , Soares Pedro , Rito Teresa
Published: August 2022

Despite the importance of ancient DNA for understanding human prehistoric dispersals, poor survival means that data remain sparse for many areas in the tropics, including in Africa. In such instances, analysis of contemporary genomes remains invaluable. One promising approach is founder analysis, which identifies and dates migration events in non-recombining systems. However, it has yet to be fully exploited as its application remains controversial. Here, we test the approach by evaluating the age of sub-Saharan mitogenome lineages sampled outside Africa. The analysis confirms that such lineages in the Americas date to recent centuries—the time of the Atlantic slave trade—thereby validating the approach. By contrast, in North Africa, Southwestern Asia and Europe, roughly half of the dispersal signal dates to the early Holocene, during the “greening” of the Sahara. We elaborate these results by showing that the main source regions for the two main dispersal episodes are distinct. For the recent dispersal, the major source was West Africa, but with two exceptions: South America, where the fraction from Southern Africa was greater, and Southwest Asia, where Eastern Africa was the primary source. These observations show the potential of founder analysis as both a supplement and complement to ancient DNA studies.
Mass Spectrometric Metabolic Fingerprinting of 2-Deoxy-D-Glucose (2-DG)-Induced Inhibition of Glycolysis and Comparative Analysis of Methionine Restriction versus Glucose Restriction under Perfusion Culture in the Murine L929 Model System
Authors: Volland Julian Manuel , Kaupp Johannes , Schmitz Werner , Wünsch Anna Chiara , Balint Julia , Möllmann Marc , El-Mesery Mohamed , Frackmann Kyra , Peter Leslie , Hartmann Stefan , Kübler Alexander Christian , Seher Axel
Published: August 2022

All forms of restriction, from caloric to amino acid to glucose restriction, have been established in recent years as therapeutic options for various diseases, including cancer. However, usually there is no direct comparison between the different restriction forms. Additionally, many cell culture experiments take place under static conditions. In this work, we used a closed perfusion culture in murine L929 cells over a period of 7 days to compare methionine restriction (MetR) and glucose restriction (LowCarb) in the same system and analysed the metabolome by liquid chromatography mass spectrometry (LC-MS). In addition, we analysed the inhibition of glycolysis by 2-deoxy-D-glucose (2-DG) over a period of 72 h. 2-DG induced very fast a low-energy situation by a reduced glycolysis metabolite flow rate resulting in pyruvate, lactate, and ATP depletion. Under perfusion culture, both MetR and LowCarb were established on the metabolic level. Interestingly, over the period of 7 days, the metabolome of MetR and LowCarb showed more similarities than differences. This leads to the conclusion that the conditioned medium, in addition to the different restriction forms, substantially reprogramm the cells on the metabolic level.
A Uniquely Stable Trimeric Model of SARS-CoV-2 Spike Transmembrane Domain
Authors: Aliper Elena T. , Krylov Nikolay A. , Nolde Dmitry E. , Polyansky Anton A. , Efremov Roman G.
Published: August 2022

Understanding fusion mechanisms employed by SARS-CoV-2 spike protein entails realistic transmembrane domain (TMD) models, while no reliable approaches towards predicting the 3D structure of transmembrane (TM) trimers exist. Here, we propose a comprehensive computational framework to model the spike TMD only based on its primary structure. We performed amino acid sequence pattern matching and compared the molecular hydrophobicity potential (MHP) distribution on the helix surface against TM homotrimers with known 3D structures and selected an appropriate template for homology modeling. We then iteratively built a model of spike TMD, adjusting “dynamic MHP portraits” and residue variability motifs. The stability of this model, with and without palmitoyl modifications downstream of the TMD, and several alternative configurations (including a recent NMR structure), was tested in all-atom molecular dynamics simulations in a POPC bilayer mimicking the viral envelope. Our model demonstrated unique stability under the conditions applied and conforms to known basic principles of TM helix packing. The original computational framework looks promising and could potentially be employed in the construction of 3D models of TM trimers for a wide range of membrane proteins.
Dermatopontin Influences the Development of Obesity-Associated Colon Cancer by Changes in the Expression of Extracellular Matrix Proteins
Authors: Catalán Victoria , Domench Paula , Gómez-Ambrosi Javier , Ramírez Beatriz , Becerril Sara , Mentxaka Amaia , Rodríguez Amaia , Valentí Víctor , Moncada Rafael , Baixauli Jorge , Silva Camilo , Escalada Javier , Frühbeck Gema
Published: August 2022

Dysfunctional adipose tissue (AT) in the context of obesity leads to chronic inflammation together with an altered extracellular matrix (ECM) remodelling, favouring cancer development and progression. Recently, the influence of dermatopontin (DPT) in AT remodelling and inflammation has been proposed. We aimed to evaluate the role of DPT in the development of obesity-associated colon cancer (CC). Samples obtained from 73 subjects [26 lean (LN) and 47 with obesity (OB)] were used in a case-control study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (42 without CC and 31 with CC). In vitro studies in the adenocarcinoma HT-29 cell line were performed to analyse the impact of pro- and anti-inflammatory mediators on the transcript levels of DPT as well as the effect of DPT on ECM remodelling and inflammation. Although obesity increased (p < 0.05) the circulating levels of DPT, its concentrations were significantly decreased (p < 0.05) in patients with CC. Gene expression levels of DPT in the colon from patients with CC were downregulated and, oppositely, a tendency towards increased mRNA levels in visceral AT was found. We further showed that DPT expression levels in HT-29 cells were enhanced (p < 0.05) by inflammatory factors (LPS, TNF-α and TGF-β), whereas the anti-inflammatory IL-4 decreased (p < 0.05) its expression levels. We also demonstrated that DPT upregulated (p < 0.05) the mRNA of key molecules involved in ECM remodelling (COL1A1, COL5A3, TNC and VEGFA) whereas decorin (DCN) expression was downregulated (p < 0.05) in HT-29 cells. Finally, we revealed that the adipocyte-conditioned medium obtained from volunteers with OB enhanced (p < 0.01) the expression of DPT in HT-29 and Caco-2 cells. The decreased circulating and expression levels of DPT in the colon together with the tendency towards increased levels in visceral AT in patients with CC and its influence on the expression of ECM proteins suggest a possible role of DPT in the OB-associated CC.
Evaluating the Effect of Dynamic Message Signs and Lane Control Signs on Driver Behavior in a Developing Country
Authors: Shaaban Khaled , Alsoub Mohammed
Published: August 2022

Developing countries are continuously upgrading their transportation systems. The latest improvement in Qatar, a fast-developing country in the Middle East, was the installation of dynamic message signs (DMS) and lane control signs (LCS). These signs were installed in multiple areas in the city of Doha, the capital of Qatar. However, there have been no studies in Qatar or the region regarding the effectiveness of such signs on driver behavior. This study aims to evaluate and compare the impact of DMS and LCS on driving behavior on different types of roads. A real-life driving experiment was conducted along a defined route in Doha that consists of three sections: arterial road, freeway with electronic signs, and freeway without electronic signs. The details of the trips were recorded using multiple methods. The results showed that the introduction of DMS and LCS did not significantly affect speed compliance. The results also indicated that LCS and DMS did not have a major effect on other driver behavior variables such as harsh braking and lane changing. The study provided several recommendations to road authorities concerning the deployment of electronic signs and highlighted a few topics for future research work.
Evaluation of Entomopathogenic Nematodes against Red Palm Weevil, Rhynchophorus ferrugineus (Olivier) (Coleoptera: Curculionidae)
Authors: Rehman Gul , Mamoon-ur-Rashid Muhammad
Published: August 2022

Entomopathogenic nematodes play a pivotal role as biocontrol agents for different species of insect pests, including the red palm weevil. In the current investigation, the infective capabilities of four species of entomopathogenic nematodes, including Hetrerorhabditis bacteriophora, Steinernema feltiae, Steinernema glaseri, and Steinernema carpocapsae, were evaluated against larvae, pupae, and adult red palm weevil under laboratory and field conditions. The pathogenic potential of selected nematode species was assessed based on dissection and adult emergence of weevils. Our results indicated that S. carpocapsae and H. bacteriophora, with a respective 94.68 and 92.68% infection rate, were the most effective EPN species against red palm weevil larvae. Focusing on adult emergence, the aforementioned EPNs were comparatively less pathogenic and resulted in 63.60 and 60.20% infested pupae, respectively. It is noted that adult emergence is the better option to evaluate the pathogenic potential of EPNs, compared with the dissection of insects. The S. carpocapsae was found to be most effective against the 6th instar larvae of the red palm weevil and caused 100% mortality at 240 h after treatment. On the other hand, S. glaseri and S. feltiae were found to be the least pathogenic and caused 70 and 76% mortality, respectively. All of the evaluated nematode species were found to be highly infective under field conditions. The S. carpocapsae was found to be the most pathogenic, causing 83.60% mortality of the red palm weevil. However, the tested nematodes were found most effective against larvae, followed by adult weevils, but their effect was minimal against the pupae of red palm weevils. Based on these findings, we conclude that the S. carpocapsae and H. bacteriophora could be used as a sustainable option for the efficient management of the red palm weevil.
Ethanol Infusion of Vein of Marshall for the Treatment of Persistent Atrial Fibrillation: The Basics and Clinical Practice
Authors: He Bo , Zhao Fang , Yu Wenxi , Li Yi , Wu Xiaoyan , Lu Zhibing
Published: August 2022

Catheter ablation for persistent atrial fibrillation (PeAF) is particularly challenging, as the clinical outcomes are modest. Pulmonary vein isolation (PVI) plus linear ablation is one of the main strategies for PeAF ablation. Completely durable transmural lesions are difficult to achieve by catheter ablation during mitral isthmus ablation. The ligament of Marshall contains the vein of Marshall (VOM), myocardial tracts and innervation, and serves as arrhythmogenic foci that make it an attractive target in catheter ablation of atrial fibrillation. Additionally, it co-localizes with the mitral isthmus, and may serve as a part of the perimitral isthmus reentrant circuit. Ethanol infusion into the VOM results in rapid ablation of the neighboring myocardium and its innervation. Its incorporation into PVI significantly increases the success rate of mitral isthmus block and the clinical outcome of PeAF ablation.
A Systematic Review of Personalized Health Applications through Human–Computer Interactions (HCI) on Cardiovascular Health Optimization
Authors: Quazi Sameer , Malik Javid Ahmad
Published: August 2022

Introduction: Currently, the deployment of human–computer interactive technologies to provide personalized care has grown and immensely taken shape in most healthcare settings. With the increasing growth of the internet and technology, personalized health interventions including smartphones, associated apps, and other interventions demonstrate prowess in various health fields, including cardiovascular management. This systematic review thus examines the effectiveness of various human–computer interactions technologies through telehealth (mainly eHealth) towards optimizing the outcomes in cardiovascular treatment. Methods: A comprehensive search of MEDLINE, EMBASE, and CINAHL databases using key terms was conducted from 2000 to November 2021 to identify suitable studies that explored the use of human–computer interaction technologies to provide a personalized care approach to facilitate bolstered outcomes for cardiovascular patients, including the elderly. The included studies were assessed for quality and risk of bias, and the authors undertook a data extraction task. Results: Ten studies describing the use of a mix of personalized health app (mHealth) interventions were identified and included in the study. Among the included studies, nine of them were randomized trials. All of the studies demonstrated the effectiveness of various personalized health interventions in maximizing the benefits of cardiovascular disease treatment. Conclusions: Personalized health application interventions through precision medicine has great potential to boost cardiovascular disease management outcomes, including rehabilitation. Fundamentally, since each intervention’s focus might differ based on the disease and outcome preference, it is recommended that more research be done to tailor the interventions to specific disease and patient outcome expectations.
Corneal Nerve Changes Observed by In Vivo Confocal Microscopy in Patients Receiving Oxaliplatin for Colorectal Cancer: The COCO Study
Authors: Tyler Ellen F. , McGhee Charles N. J. , Lawrence Benjamin , Braatvedt Geoffrey D. , Mankowski Joseph L. , Oakley Jonathan D. , Sethi Sargun , Misra Stuti L.
Published: August 2022

An objective method of early identification of people at risk of chemotherapy-induced peripheral neuropathy is needed to minimize long-term toxicity and maximize dose intensity. The aims of the study were to observe corneal nerve microstructure and corneal sensitivity changes and peripheral neuropathy in patients receiving oxaliplatin, and to determine its association with corneal parameters at different stages of treatment and assess utility as non-invasive markers to detect and monitor peripheral neuropathy. Twenty-three patients scheduled to receive oxaliplatin chemotherapy with intravenous 5-FU for gastro-intestinal cancer were recruited and followed up with for 12 months. Ocular examinations including corneal and retinal evaluations, alongside peripheral neuropathy assessment, were performed. The corneal nerve density did not show significant change after chemotherapy when measured with a widely used semi-automated program or an automated analysis technique. Macula and optic nerve function did not change during or after oxaliplatin chemotherapy. However, the corneal nerve density modestly correlated with clinical peripheral neuropathy after 20 weeks of chemotherapy (r = 0.61, p = 0.01) when peripheral neuropathy is typical most profound, and corneal nerve sensitivity correlated with neuropathy at 12 (r = 0.55, p = 0.01) and 20 weeks (r = 0.64, p = 0.006). In conclusion, corneal changes detected on confocal microscopy show moderate association with peripheral neuropathy, indicating their potential to identify the development of oxaliplatin-induced peripheral neuropathy. However, further studies are required to confirm these findings.
The Association between Neoadjuvant Radio-Chemotherapy and Prolonged Healing of Anastomotic Leakage after Esophageal Resection Treated with EndoVAC Therapy
Authors: Seika Philippa , Biebl Matthias , Raakow Jonas , Berndt Nadja , Feldbrügge Linda , Maurer Max Magnus , Dobrindt Eva , Thuss-Patience Peter , Pratschke Johann , Denecke Christian
Published: August 2022

(1) Background: Endoscopic vacuum therapy (EVT) has become the mainstay in the treatment of early anastomotic leakage (AL) after esophageal resection. The effect of nRCT on the efficacy of EVT is currently unknown. (2) Methods: Data of 427 consecutive patients undergoing minimally invasive esophagectomy between 2013 and 2022 were analyzed. A total of 26 patients received EVT for AL after esophagectomy between 2010 and 2021. We compared a cohort of 13 patients after treatment with EVT for anastomotic leakage after neoadjuvant radiochemotherapy (nRCT) with a control group of 13 patients after neoadjuvant chemotherapy (nCT) using inverse propensity score weighting to adjust for baseline characteristics between the groups. EVT therapy was assessed regarding patient survival, treatment failure as defined by a change in treatment to stent/operation, duration of treatment, and secondary complications. Statistical analysis was performed using linear regression analysis. (3) Results: Time to EVT after initial tumor resection did not vary between the groups. The duration of EVT was longer in patients after nRCT (14.69 days vs. 20.85 days, p = 0.002) with significantly more interventions (4.38 vs. 6.85, p = 0.001). The success rate of EVT did not differ between the two groups (nCT n = 8 (61.54%) vs. nCT n = 5 (38.46%), p = 0.628). The rate of operative revision did not vary between the groups. Importantly, no mortality was reported within 30 days and 90 days in both groups. (4) Conclusions: EVT is a valuable tool for the management of AL after esophageal resection in patients after nRCT. While the success rates were comparable, EVT was associated with a significantly longer treatment duration. Anastomotic leakages after nRCT often require prolonged and multimodal treatment strategies while innovative strategies such as prophylactic endoVAC placement or use of a VAC-Stent may be considered.
Burden of Atopic Dermatitis in Adults in Greece: Results from a Nationwide Survey
Authors: Gregoriou Stamatis , Stefanou Garyfallia , Kontodimas Stathis , Sfaelos Konstantinos , Zavali Maria , Vakirlis Efstratios , Kourlaba Georgia
Published: August 2022

The objective was to describe the AD burden in terms of quality of life (QoL), sleep, social life, work productivity, and resource utilization in Greece and assess the impact of disease severity. A nationwide cross-sectional survey was conducted. The questionnaire consisted of socioeconomic factors, medical history, AD screening, AD severity, QoL, sleep difficulties, social activities, and work productivity questions. AD was defined using the UK Working Party criteria (UKWP cohort) and a patient-reported AD diagnosis from a physician (Expert Diagnosis cohort). Self-reported moderate/severe AD was estimated using the Patient-Oriented Eczema Measure (POEM). In the UKWP cohort, the AD effect on QoL was moderate/extremely large in 84.3% of moderate/severe AD (vs. 55.7% in mild; p = 0.016), while in the Expert Diagnosis cohort, it was 72.2% (vs. 22.8%; p < 0.001). Disease severity was associated with a higher impact on sleep and social activities. Overall work impairment was high in both mild (32.7%) and moderate/severe (48.5%) AD of the UKWP cohort, while among the Expert Diagnosis cohort, it was significantly higher among those with moderate/severe (31.2%) versus mild AD (11.9%; p < 0.001). The AD burden in Greece is significant, especially for those in moderate/severe AD stages. Acknowledging this burden is the first step toward applying healthcare decisions that will benefit patients and the community.
Comparison of 3-Year Outcomes between Early and Delayed Invasive Strategies in Older and Younger Adults with Non-ST-Segment Elevation Myocardial Infarction Undergoing New-Generation Drug-Eluting Stent Implantation
Authors: Kim Yong Hoon , Her Ae-Young , Rha Seung-Woon , Choi Cheol Ung , Choi Byoung Geol , Kim Ji Bak , Park Soohyung , Kang Dong Oh , Park Ji Young , Park Sang-Ho , Jeong Myung Ho
Published: August 2022

We evaluated the 3-year clinical outcomes of early invasive (EI) and delayed invasive (DI) strategies in older and younger adults with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing successful new-generation drug-eluting stent (DES) implantation to reflect current real-world practice. Overall, 4513 patients with NSTEMI were recruited from the Korea Acute Myocardial Infarction Registry-National Institute of Health and divided into two groups according to age: group A (age ≥ 65 years, n = 2253) and group B (age < 65 years, n = 2260). These two groups were further divided into two subgroups: group EI (A1 and B1) and DI (A2 and B2). The primary clinical outcome was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), defined as all-cause death, recurrent MI (re-MI), any repeat coronary revascularization, or stroke. The secondary clinical outcome was definite or probable stent thrombosis (ST). In both groups A and B, after multivariable-adjusted and propensity score-adjusted analyses, MACCE (group A, p = 0.137 and p = 0.255, respectively; group B, p = 0.171 and p = 0.135, respectively), all-cause death, cardiac death (CD), non-CD, re-MI, any repeat revascularization, stroke, and ST rates were similar between the EI and DI groups. When including only those with complex lesions, the primary and secondary clinical outcomes were not significantly different between the EI and DI groups. In the era of new-generation DESs, major clinical outcomes were not significantly different between the EI and DI strategies in both older and younger adults with NSTEMI.
Hypofractionated Radiotherapy in Intermediate-Risk Prostate Cancer Patients: Long-Term Results
Authors: Valeriani Maurizio , Di Staso Mario , Facondo Giuseppe , Vullo Gianluca , De Sanctis Vitaliana , Gravina Giovanni Luca , di Genesio Pagliuca Milena , Osti Mattia Falchetto , Bonfili Pierluigi
Published: August 2022

Background: To evaluate outcomes in terms of survival and toxicity in a series of intermediate-risk prostate cancer (PCa) patients treated with hypofractionated radiotherapy (HyRT) + hormonal therapy (HT) with or without image guidance (IGRT) and to investigate the impact of different variables. Methods: This is a multi-centric study. From January 2005 to December 2019, we treated 313 intermediate-risk PCa patients (T2b–T2c, Gleason score 7, or pre-treatment PSA 10 to 20 ng/mL) with HyRT. Patients received 54.75 Gy in 15 fractions in 5 weeks plus 9 months of neo-adjuvant, concomitant, and adjuvant HT with or without IGRT. Results: Median follow-up was 91.6 months (range 5.1–167.8 months). Median OS was not reached, and the 8- and 10-year OS was 81.9% and 72.4%, respectively. Median CSS was not reached, and the 8- and 10-year CSS was 97.9% and 94.5%, respectively. PSA at first follow-up <0.8 ng/mL was significantly related to better oncological outcomes (CSS, bRFS, LRFS, cPFS, and MFS) in both univariate and multivariate analysis. After Propensity Score matching, grade 2–3 acute and cumulative late GU (p = 0.153 and p = 0.581, respectively) and GI (p = 0.196 and p = 0.925, respectively) toxicity were not statistically different in patients treated with or without IGRT. Conclusions: HyRT is effective and safe regardless of the use of IGRT. PSA at first follow-up is an easily accessible prognostic factor that may help the clinicians to identify patients who require a treatment intensification.
Outcomes of Deep Sclerectomy following Failed XEN Gel Stent Implantation in Open-Angle Glaucoma: A Prospective Study
Authors: Bravetti Giorgio Enrico , Gillmann Kevin , Rao Harsha L. , Mermoud André , Mansouri Kaweh
Published: August 2022

Background: The purpose of this study is to evaluate the outcome of deep sclerectomy (DS) as a secondary procedure following failed ab-interno XEN gel stent implantation in patients with open-angle glaucoma. Methods: Prospective, single-center, non-randomized, interventional study. Consecutive eyes that underwent mitomycin C (MMC) augmented XEN gel stent surgery, with uncontrolled intraocular pressure (IOP) or signs of disease progression, were included to undergo MMC-augmented DS. Primary efficacy outcome was surgical success, defined as complete when the unmedicated IOP was 12 mmHg or less, or 15 mmHg or less and 20% lower than at the timing of XEN failure and defined as qualified when the IOP fulfilled the same conditions with fewer medications than before deep sclerectomy. Secondary measures were mean reduction in IOP and in the number of medications, and the rates of complications. Results: Seventeen eyes were enrolled with a mean age of 72.1 ± 8.2 years (66.7% women). The mean follow-up was 20.1 ± 4.9 months, with more than 12-month data available from 15 eyes. Following DS, IOP decreased significantly from 22.6 ± 5.3 mmHg to 12.3 ± 5.5 (45.6%; p < 0.001). Antiglaucoma medications dropped from 1.1 ± 0.9 to 0.3 ± 0.7. Complete success was obtained in 40% of eyes using the threshold of 12 mmHg or less and a 20% decrease of IOP, and in 60% using the 15 mmHg or less threshold. Adverse events were observed in 20% of eyes (bleb leakage (13.3%); hypotony (6.7%)). No cases of choroidal detachment or hypotony maculopathy were reported. Conclusions: Failed XEN gel stent implantation does not seem to negatively affect the safety and efficacy of subsequent deep sclerectomy surgery.
Immune Checkpoint Inhibitors’ Associated Renal Toxicity: A Series of 12 Cases
Authors: Palamaris Kostas , Alexandris Dimitrios , Stylianou Kostas , Giatras Ioannis , Stofas Anastasios , Kaitatzoglou Christina , Migkou Magda , Goutas Dimitrios , Psimenou Erasmia , Theodoropoulou Eleni , Theocharis Stamatios , Alevizopoulos Nektarios , Kastritis Efstathios , Gerakis Alexandros , Gakiopoulou Harikleia
Published: August 2022

We present a series of twelve patients, bearing a wide range of solid malignancies, who received either PD-L1 or a combination of PD-L1 and CTLA-4 inhibitors. Following immunotherapy administration, they exhibited the clinical signs indicative of renal toxicity, including increased serum creatinine levels, proteinuria, nephrotic syndrome and/or hematuria. All patients underwent renal biopsy. Results: All cases demonstrated some degree of interstitial inflammation and tubular injury, while in five patients, glomerular alterations consistent with a specific glomerulopathy were also observed: secondary “lupus-like” membranous glomerulopathy in two cases and membranoproliferative glomerulonephritis, IgA glomerulonephritis and secondary AA amyloidosis in each of the remaining three patients. The two patients with “lupus-like” nephritis and the one with amyloidosis experienced nephrotic syndrome, while their creatinine was within normal range. In the remaining nine cases, deterioration of renal function was the main manifestation. Conclusion: Our findings harmonize with bibliographical data that identify tubulointerstitial nephritis as the most frequent histological lesion related to ICIs administration. The preferential involvement of tubulointerstitial tissue could be associated with the reported higher expression levels of PD-L1 on tubular epithelial cells, compared to glomeruli. On the other hand, glomerular involvement is probably a consequence of a systemic immune system reconstruction, induced by immune-checkpoints inhibition.
The Effectiveness of Plasma Rich in Growth Factors (PRGF) in the Treatment of Nerve Compression Syndromes of the Upper Extremity: A Retrospective Observational Clinical Study
Authors: Galán Víctor , Iñigo-Dendariarena Iñaki , Galán Iñigo , Prado Roberto , Padilla Sabino , Anitua Eduardo
Published: August 2022

Background: Nerve compression syndromes of the upper extremity are a common cause of neuropathic pain and functional impairment. Recently, platelet-rich plasma (PRP) infiltrations have emerged as an effective biological approach to the treatment of this type of injury. The objectives of this retrospective observational study were to assess clinical improvement in patients with median and ulnar nerve entrapment syndrome after undergoing biologically-assisted nerve release surgery with plasma-rich-in-growth-factors (PRGF) technology. Methods: Participants (n = 39) with moderate-to-severe nerve compression syndrome of the upper limb diagnosed by both electromyography and clinical examination, and who were treated with PRGF, were identified from the center’s medical records. The evaluation was based on patient-reported outcomes. Pre- and post-treatment differences in the Visual analog scale (VAS), the Boston carpal tunnel questionnaire (BCTQ), and the Quick-DASH score were assessed. Results: Three study groups were conducted: patients with carpal tunnel syndrome (n = 16), with recurrent carpal tunnel syndrome (n = 8), and with ulnar nerve entrapment (n = 15). The median follow-up was 12 months (interquartile range (IQR), 9–16). In comparison to pre-treatment values, all three study groups obtained statistically significant improvements for the three analyzed scales at the end of the follow-up, with p < 0.001 for all scales in the carpal tunnel syndrome and ulnar nerve entrapment groups and p < 0.01 for all scales in the recurrent carpal tunnel syndrome group. There were no serious adverse effects in the analyzed patients. Conclusion: PRGF-assisted open surgical nerve release treatment (intraneural and perineural liquid PRGF infiltrations and nerve wrapping with PRGF membrane) exerts long-term beneficial effects on pain reduction and functional improvement in the nerve and nerve–muscle unit in patients with upper extremity compression syndromes.
Personalized Surgery Service in a Tertiary Hospital: A Method to Increase Effectiveness, Precision, Safety and Quality in Maxillofacial Surgery Using Custom-Made 3D Prostheses and Implants
Authors: Pamias-Romero Jorge , Masnou-Pratdesaba Joan , Sáez-Barba Manel , de-Pablo-García-Cuenca Alba , Siurana-Montilva Sahyly , Sala-Cunill Anna , Valls-Comamala Victòria , Pujol-Pina Rosa , Bescós-Atín Coro
Published: August 2022

Personalized surgery (PS) involves virtual planning (VP) and the use of 3D printing technology to design and manufacture custom-made elements to be used during surgery. The widespread use of PS has fostered a paradigm shift in the surgical process. A recent analysis performed in our hospital—along with several studies published in the literature—showed that the extensive use of PS does not preclude the lack of standardization in the process. This means that despite the widely accepted use of this technology, standard individual roles and responsibilities have not been properly defined, and this could hinder the logistics and cost savings in the PS process. The aim of our study was to describe the method followed and the outcomes obtained for the creation of a PS service for the Oral and Maxillofacial Surgery Unit that resolves the current absence of internal structure, allows for the integration of all professionals involved and improves the efficiency and quality of the PS process. We performed a literature search on the implementation of PS techniques in tertiary hospitals and observed a lack of studies on the creation of PS units or services in such hospitals. Therefore, we believe that our work is innovative and has the potential to contribute to the implementation of PS units in other hospitals.
Pregnancies and Gynecological Follow-Up after Solid Organ Transplantation: Experience of a Decade
Authors: Bedin Alice , Carbonnel Marie , Snanoudj Renaud , Roux Antoine , Vanlieferinghen Sarah , Marchiori Claire , Hertig Alexandre , Racowsky Catherine , Ayoubi Jean-Marc
Published: August 2022

In recent years, solid organ transplantations, such as kidney or lung grafts, have been performed worldwide with an improvement of quality of life under immunosuppressive therapy and an increase in life expectancy, allowing young women to consider childbearing. In the current study, we conduct a retrospective study in two French centers for kidney and lung transplantations to evaluate the rate and outcomes of pregnancies, contraception and gynecological monitoring for women under 40 years old who underwent solid organ transplantation. Among 210 women, progestin was the most widely used contraceptive method. Of the 210 women, 24 (11.4%) conceived 33 pregnancies of which 25 (75.8%) were planned with an immunosuppressant therapy switch. Of the 33 pregnancies, 7 miscarried (21.2%) and 21 (63.7%) resulted in a live birth with a high rate of pre-eclampsia (50%). No graft rejections were observed during pregnancies. Among the deliveries, 19 were premature (90.5%, mostly due to induced delivery) and the C-section rate was high (52.4%). No particular pathology was identified among newborns. We conclude that pregnancies following solid organ transplantation are feasible, and while they are at an increased risk of pre-eclampsia and prematurity, they should still be permitted with close surveillance by a multidisciplinary care team.