bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Rhamnolipids and Ionic Cross-Linking Conditions on the Mechanical Properties of Alginate Hydrogels as a Model Bacterial Biofilm
Authors: Czaplicka Natalia , Mania Szymon , Konopacka-Łyskawa Donata
Published: June 2021

The literature indicates the existence of a relationship between rhamnolipids and bacterial biofilm, as well as the ability of selected bacteria to produce rhamnolipids and alginate. However, the influence of biosurfactant molecules on the mechanical properties of biofilms are still not fully understood. The aim of this research is to determine the effect of rhamnolipids concentration, CaCl2 concentration, and ionic cross-linking time on the mechanical properties of alginate hydrogels using a Box–Behnken design. The mechanical properties of cross-linked alginate hydrogels were characterized using a universal testing machine. It was assumed that the addition of rhamnolipids mainly affects the compression load, and the value of this parameter is lower for hydrogels produced with biosurfactant concentration below CMC than for hydrogels obtained in pure water. In contrast, the addition of rhamnolipids in an amount exceeding CMC causes an increase in compression load. In bacterial biofilms, the presence of rhamnolipid molecules does not exceed the CMC value, which may confirm the influence of this biosurfactant on the formation of the biofilm structure. Moreover, rhamnolipids interact with the hydrophobic part of the alginate copolymer chains, and then the hydrophilic groups of adsorbed biosurfactant molecules create additional calcium ion trapping sites.
NaCl-Induced Elicitation Alters Physiology and Increases Accumulation of Phenolic Compounds in Melissa officinalis L.
Authors: Hawrylak-Nowak Barbara , Dresler Sławomir , Stasińska-Jakubas Maria , Wójciak Magdalena , Sowa Ireneusz , Matraszek-Gawron Renata
Published: June 2021

In nature, plants usually produce secondary metabolites as a defense mechanism against environmental stresses. Different stresses determine the chemical diversity of plant-specialized metabolism products. In this study, we applied an abiotic elicitor, i.e., NaCl, to enhance the biosynthesis and accumulation of phenolic secondary metabolites in Melissa officinalis L. Plants were subjected to salt stress treatment by application of NaCl solutions (0, 50, or 100 mM) to the pots. Generally, the NaCl treatments were found to inhibit the growth of plants, simultaneously enhancing the accumulation of phenolic compounds (total phenolics, soluble flavonols, anthocyanins, phenolic acids), especially at 100 mM NaCl. However, the salt stress did not disturb the accumulation of photosynthetic pigments and proper functioning of the PS II photosystem. Therefore, the proposed method of elicitation represents a convenient alternative to cell suspension or hydroponic techniques as it is easier and cheaper with simple application in lemon balm pot cultivation. The improvement of lemon balm quality by NaCl elicitation can potentially increase the level of health-promoting phytochemicals and the bioactivity of low-processed herbal products.
Hyaluronan and the Fascial Frontier
Authors: Pratt Rebecca L.
Published: June 2021

The buzz about hyaluronan (HA) is real. Whether found in face cream to increase water volume loss and viscoelasticity or injected into the knee to restore the properties of synovial fluid, the impact of HA can be recognized in many disciplines from dermatology to orthopedics. HA is the most abundant polysaccharide of the extracellular matrix of connective tissues. HA can impact cell behavior in specific ways by binding cellular HA receptors, which can influence signals that facilitate cell survival, proliferation, adhesion, as well as migration. Characteristics of HA, such as its abundance in a variety of tissues and its responsiveness to chemical, mechanical and hormonal modifications, has made HA an attractive molecule for a wide range of applications. Despite being discovered over 80 years ago, its properties within the world of fascia have only recently received attention. Our fascial system penetrates and envelopes all organs, muscles, bones and nerve fibers, providing the body with a functional structure and an environment that enables all bodily systems to operate in an integrated manner. Recognized interactions between cells and their HA-rich extracellular microenvironment support the importance of studying the relationship between HA and the body’s fascial system. From fasciacytes to chronic pain, this review aims to highlight the connections between HA and fascial health.
Impact of Leptin on Periodontal Ligament Fibroblasts during Mechanical Strain
Authors: Schröder Agnes , Meyer Andrea , Spanier Gerrit , Damanaki Anna , Paddenberg Eva , Proff Peter , Kirschneck Christian
Published: June 2021

Orthodontic treatment to correct dental malocclusions leads to the formation of pressure zones in the periodontal ligament resulting in a sterile inflammatory reaction, which is mediated by periodontal ligament fibroblasts (PDLF). Leptin levels are elevated in obesity and chronic inflammatory responses. In view of the increasing number of orthodontic patients with these conditions, insights into effects on orthodontic treatment are of distinct clinical relevance. A possible influence of leptin on the expression profile of PDLF during simulated orthodontic mechanical strain, however, has not yet been investigated. In this study, PDLF were exposed to mechanical strain with or without different leptin concentrations. The gene and protein expression of proinflammatory and bone-remodelling factors were analysed with RT-qPCR, Western-blot and ELISA. The functional analysis of PDLF-induced osteoclastogenesis was analysed by TRAP (tartrate-resistant acid phosphatase) staining in coculture with human macrophages. Pressure-induced increase of proinflammatory factors was additionally elevated with leptin treatment. PDLF significantly increased RANKL (receptor activator of NF-kB ligand) expression after compression, while osteoprotegerin was downregulated. An additional leptin effect was demonstrated for RANKL as well as for subsequent osteoclastogenesis in coculture after TRAP staining. Our results suggest that increased leptin concentrations, as present in obese patients, may influence orthodontic tooth movement. In particular, the increased expression of proinflammatory factors and RANKL as well as increased osteoclastogenesis can be assumed to accelerate bone resorption and thus the velocity of orthodontic tooth movement in the orthodontic treatment of obese patients.
The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production
Authors: Simões Inês C. M. , Amorim Ricardo , Teixeira José , Karkucinska-Wieckowska Agnieszka , Carvalho Adriana , Pereira Susana P. , Simões Rui F. , Szymanska Sylwia , Dąbrowski Michał , Janikiewicz Justyna , Dobrzyń Agnieszka , Oliveira Paulo J. , Potes Yaiza , Wieckowski Mariusz R.
Published: June 2021

The progression of non-alcoholic fatty liver (NAFL) into non-alcoholic steatohepatitis implicates multiple mechanisms, chief of which is mitochondrial dysfunction. However, the sequence of events underlying mitochondrial failure are still poorly clarified. In this work, male C57BL/6J mice were fed with a high-fat plus high-sucrose diet for 16, 20, 22, and 24 weeks to induce NAFL. Up to the 20th week, an early mitochondrial remodeling with increased OXPHOS subunits levels and higher mitochondrial respiration occurred. Interestingly, a progressive loss of mitochondrial respiration along “Western diet” feeding was identified, accompanied by higher susceptibility to mitochondrial permeability transition pore opening. Importantly, our findings prove that mitochondrial alterations and subsequent impairment are independent of an excessive mitochondrial reactive oxygen species (ROS) generation, which was found to be progressively diminished along with disease progression. Instead, increased peroxisomal abundance and peroxisomal fatty acid oxidation-related pathway suggest that peroxisomes may contribute to hepatic ROS generation and oxidative damage, which may accelerate hepatic injury and disease progression. We show here for the first time the sequential events of mitochondrial alterations involved in non-alcoholic fatty liver disease (NAFLD) progression and demonstrate that mitochondrial ROS are not one of the first hits that cause NAFLD progression.
Quercetin Protects Human Thyroid Cells against Cadmium Toxicity
Authors: Capriglione Francesca , Maiuolo Jessica , Celano Marilena , Damante Giuseppe , Russo Diego , Bulotta Stefania , Maggisano Valentina
Published: June 2021

Various natural compounds have been successfully tested for preventing or counteracting the toxic effects of exposure to heavy metals. In this study, we analyzed the effects of cadmium chloride (CdCl2) on immortalized, non-tumorigenic thyroid cells Nthy-ori-3-1. We investigated the molecular mechanism underlying its toxic action as well as the potential protective effect of quercetin against CdCl2-induced damage. CdCl2 suppressed cell growth in a dose- and time-dependent manner (IC50 value ~10 μM) associated with a decrease in levels of phospho-ERK. In addition, CdCl2 elicited an increase in reactive oxygen species (ROS) production and lipid peroxidation. A significant increase in GRP78, an endoplasmic reticulum (ER) stress-related protein, was also observed. Supplementation of quercetin counteracted the growth-inhibiting action of CdCl2 by recovering ERK protein phosphorylation levels, attenuating ROS overproduction, decreasing MDA content and reducing the expression of GRP78 in cells exposed to CdCl2. Thus, in addition to revealing the molecular effects involved in cadmium-induced toxicity, the present study demonstrated, for the first time, a protective effect of quercetin against cadmium-induced damages to normal thyroid cells.
Complement System and Potential Therapeutics in Age-Related Macular Degeneration
Authors: Park Young Gun , Park Yong Soo , Kim In-Beom
Published: June 2021

Age-related macular degeneration (AMD) is a complex multifactorial disease characterized in its late form by neovascularization (wet type) or geographic atrophy of the retinal pigment epithelium cell layer (dry type). The complement system is an intrinsic component of innate immunity. There has been growing evidence that the complement system plays an integral role in maintaining immune surveillance and homeostasis in AMD. Based on the association between the genotypes of complement variants and AMD occurrence and the presence of complement in drusen from AMD patients, the complement system has become a therapeutic target for AMD. However, the mechanism of complement disease propagation in AMD has not been fully understood. This concise review focuses on an overall understanding of the role of the complement system in AMD and its ongoing clinical trials. It provides further insights into a strategy for the treatment of AMD targeting the complement system.
GMI, an Immunomodulatory Peptide from Ganoderma microsporum, Restrains Periprosthetic Joint Infections via Modulating the Functions of Myeloid-Derived Suppressor Cells and Effector T Cells
Authors: Peng Kuo-Ti , Chen Jiun-Liang , Kuo Liang-Tseng , Yu Pei-An , Hsu Wei-Hsiu , Lee Chiang-Wen , Chang Pey-Jium , Huang Tsung-Yu
Published: June 2021

Periprosthetic joint infections (PJIs) caused by Staphylococcus aureus infection are difficult to treat due to antibiotic resistance. It is known that the biofilms from methicillin-resistant S. aureus (MRSA) promote expansion of myeloid-derived suppressor cells (MDSCs) to suppress T-cell proliferation and benefit bacterial infections. This study finds that GMI, a fungal immunomodulatory peptide isolated from Ganoderma microsporum, suppresses MDSC expansion to promote the proliferation of cytotoxic T cells. The enhancement is likely attributed to increased expression of IL-6 and TNF-α and reduction in ROS expression. Similar beneficial effects of GMI on the suppression of MDSC expansion and IL-6 expression are also observed in the whole blood and reduces the accumulation of MDSCs in the infected bone region in a mouse PJI infection model. This study shows that GMI is potentially useful for treating S. aureus-induced PJIs.
SIRT3 Overexpression Ameliorates Asbestos-Induced Pulmonary Fibrosis, mt-DNA Damage, and Lung Fibrogenic Monocyte Recruitment
Authors: Cheresh Paul , Kim Seok-Jo , Jablonski Renea , Watanabe Satoshi , Lu Ziyan , Chi Monica , Helmin Kathryn A. , Gius David , Budinger G. R. Scott , Kamp David W.
Published: June 2021

Alveolar epithelial cell (AEC) mitochondrial (mt) DNA damage and fibrotic monocyte-derived alveolar macrophages (Mo-AMs) are implicated in the pathobiology of pulmonary fibrosis. We showed that sirtuin 3 (SIRT3), a mitochondrial protein regulating cell fate and aging, is deficient in the AECs of idiopathic pulmonary fibrosis (IPF) patients and that asbestos- and bleomycin-induced lung fibrosis is augmented in Sirt3 knockout (Sirt3−/−) mice associated with AEC mtDNA damage and intrinsic apoptosis. We determined whether whole body transgenic SIRT3 overexpression (Sirt3Tg) protects mice from asbestos-induced pulmonary fibrosis by mitigating lung mtDNA damage and Mo-AM recruitment. Crocidolite asbestos (100 µg/50 µL) or control was instilled intratracheally in C57Bl6 (Wild-Type) mice or Sirt3Tg mice, and at 21 d lung fibrosis (histology, fibrosis score, Sircol assay) and lung Mo-AMs (flow cytometry) were assessed. Compared to controls, Sirt3Tg mice were protected from asbestos-induced pulmonary fibrosis and had diminished lung mtDNA damage and Mo-AM recruitment. Further, pharmacologic SIRT3 inducers (i.e., resveratrol, viniferin, and honokiol) each diminish oxidant-induced AEC mtDNA damage in vitro and, in the case of honokiol, protection occurs in a SIRT3-dependent manner. We reason that SIRT3 preservation of AEC mtDNA is a novel therapeutic focus for managing patients with IPF and other types of pulmonary fibrosis.
Plumbagin, a Natural Product with Potent Anticancer Activities, Binds to and Inhibits Dihydroorotase, a Key Enzyme in Pyrimidine Biosynthesis
Authors: Guan Hong-Hsiang , Huang Yen-Hua , Lin En-Shyh , Chen Chun-Jung , Huang Cheng-Yang
Published: June 2021

Dihydroorotase (DHOase) is the third enzyme in the de novo biosynthesis pathway for pyrimidine nucleotides, and an attractive target for potential anticancer chemotherapy. By screening plant extracts and performing GC–MS analysis, we identified and characterized that the potent anticancer drug plumbagin (PLU), isolated from the carnivorous plant Nepenthes miranda, was a competitive inhibitor of DHOase. We also solved the complexed crystal structure of yeast DHOase with PLU (PDB entry 7CA1), to determine the binding interactions and investigate the binding modes. Mutational and structural analyses indicated the binding of PLU to DHOase through loop-in mode, and this dynamic loop may serve as a drug target. PLU exhibited cytotoxicity on the survival, migration, and proliferation of 4T1 cells and induced apoptosis. These results provide structural insights that may facilitate the development of new inhibitors targeting DHOase, for further clinical anticancer chemotherapies.
Phenotyping the Prediabetic Population—A Closer Look at Intermediate Glucose Status and Cardiovascular Disease
Authors: Barbu Elena , Popescu Mihaela-Roxana , Popescu Andreea-Catarina , Balanescu Serban-Mihai
Published: June 2021

Even though the new thresholds for defining prediabetes have been around for more than ten years, there is still controversy surrounding the precise characterization of this intermediate glucose metabolism status. The risk of developing diabetes and macro and microvascular disease linked to prediabetes is well known. Still, the prediabetic population is far from being homogenous, and phenotyping it into less heterogeneous groups might prove useful for long-term risk assessment, follow-up, and primary prevention. Unfortunately, the current definition of prediabetes is quite rigid and disregards the underlying pathophysiologic mechanisms and their potential metabolic progression towards overt disease. In addition, prediabetes is commonly associated with a cluster of risk factors that worsen the prognosis. These risk factors all revolve around a common denominator: inflammation. This review focuses on identifying the population that needs to be screened for prediabetes and the already declared prediabetic patients who are at a higher risk of cardiovascular disease and require closer monitoring.
Osteosarcoma and Metastasis Associated Bone Degradation—A Tale of Osteoclast and Malignant Cell Cooperativity
Authors: Nørregaard Kirstine Sandal , Jürgensen Henrik Jessen , Gårdsvoll Henrik , Engelholm Lars Henning , Behrendt Niels , Søe Kent
Published: June 2021

Cancer-induced bone degradation is part of the pathological process associated with both primary bone cancers, such as osteosarcoma, and bone metastases originating from, e.g., breast, prostate, and colon carcinomas. Typically, this includes a cancer-dependent hijacking of processes also occurring during physiological bone remodeling, including osteoclast-mediated disruption of the inorganic bone component and collagenolysis. Extensive research has revealed the significance of osteoclast-mediated bone resorption throughout the course of disease for both primary and secondary bone cancer. Nevertheless, cancer cells representing both primary bone cancer and bone metastasis have also been implicated directly in bone degradation. We will present and discuss observations on the contribution of osteoclasts and cancer cells in cancer-associated bone degradation and reciprocal modulatory actions between these cells. The focus of this review is osteosarcoma, but we will also include relevant observations from studies of bone metastasis. Additionally, we propose a model for cancer-associated bone degradation that involves a collaboration between osteoclasts and cancer cells and in which both cell types may directly participate in the degradation process.
End-User Needs of Fragmented Databases in Higher Education Data Analysis and Decision Making
Authors: Briggs Amanda , Cafaro Francesco
Published: June 2021

In higher education, a wealth of data is available to advisors, recruiters, marketers, and program directors. These large datasets can be accessed using an array of data analysis tools that may lead users to assume that data sources conflict with one another. As users identify new ways of accessing and analyzing these data, they deviate from existing work practices and sometimes create their own databases. This study investigated the needs of end users who are accessing these seemingly fragmented databases. Analysis of a survey completed by eighteen users and ten semi-structured interviews from five colleges and universities highlighted three recurring themes that affect work practices (access, understandability, and use), as well as a series of challenges and opportunities for the design of data gateways for higher education. We discuss a set of broadly applicable design recommendations and five design functionalities that the data gateways should support: training, collaboration, tracking, definitions and roadblocks, and time.
Bed Bugs (Hemiptera: Cimicidae) Population Diversity and First Record of Cimex hemipterus in Paris
Authors: Chebbah Dahlia , Elissa Nohal , Sereno Denis , Hamarsheh Omar , Marteau Anthony , Jan Julie , Izri Arezki , Akhoundi Mohammad
Published: June 2021

Cimex lectularius and C. hemipterus are blood-sucking insects with a long history of presence in human communities. We investigated the molecular diversity of the bed bug population of Paris and its suburb cities using cytochrome oxidase 1 (CO1) sequencing. A total of 1211 specimens belonging to different life stages were collected from 62 infested human dwellings in Paris (13 out of 20 arrondissements) and the surrounding cities (18 cities). Morphological determination and COI sequencing of 132 specimens demonstrated C. lectularius as the predominant species and, surprisingly, the presence of C. hemipterus in four infested areas of Paris and its suburb cities. Neighbor-joining tree and network analyses depicted the presence of two C. lectularius populations. Most samples from Paris and its suburb cities clustered in a major clade. The second population encompasses specimens from Paris (arrondissements 11 and 19) and its suburb cities (e.g., Bobigny, Pantin, and Montreuil) that clustered with Hungary, Czechia, and Finland. This is the second evidence for C. hemipterus infestation in France and the third in Europe, which challenges the classic pattern of C. hemipterus dispersion and implies sympatric occurrence of C. lectularius and C. hemipterus. Since Paris is one of the most popular tourist destinations in the world, our observations shed light on bed bugs’ dispersal dynamic and may help future vector control strategies.
Early Aberrant Angiogenesis Due to Elastic Fiber Fragmentation in Aortic Valve Disease
Authors: Hinton Robert B. , Juraszek Amy L. , Opoka Amy M. , Landis Benjamin J. , Smith J. Michael , Mecham Robert P. , Bove Kevin E.
Published: June 2021

Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and pathology of aortic valve tissue were assessed using histochemistry, immunohistochemistry, and electron microscopy from early-onset (<40 yo) and late-onset (≥40 yo) non-syndromic AVD specimens. To assess the effects of EFF on early AVD processes, valve tissue from Williams and Marfan syndrome patients was also analyzed. Bicuspid aortic valve was more common in early-onset AVD, and cardiovascular comorbidities were more common in late-onset AVD. Early-onset AVD specimens demonstrated angiogenesis without inflammation or atherosclerosis. A distinct pattern of elastic fiber components surrounded early-onset AVD neovessels, including increased emilin-1 and decreased fibulin-5. Different types of EFF were present in Williams syndrome (WS) and Marfan syndrome (MFS) aortic valves; WS but not MFS aortic valves demonstrated angiogenesis. Aberrant angiogenesis occurs in early-onset AVD in the absence of inflammation, implicating EFF. Elucidation of underlying mechanisms may inform the development of new pharmacologic treatments.
Role of Non-Invasive Respiratory Supports in COVID-19 Acute Respiratory Failure Patients with Do Not Intubate Orders
Authors: Medrinal Clément , Gillet Alexis , Boujibar Fairuz , Dugernier Jonathan , Zwahlen Marcel , Lamia Bouchra , Girault Christophe , Creteur Jacques , Fellrath Jean-Marc , Haesler Laurence , Lagache Laurie , Goubert Laure , Artaud Macari Elise , Taton Olivier , Gouin Philippe , Leduc Dimitri , Van Hove Olivier , Norrenberg Michelle , Prieur Guillaume , Combret Yann , Correvon Nils , Hilfiker Roger , Contal Olivier
Published: June 2021

The current gold-standard treatment for COVID-19-related hypoxemic respiratory failure is invasive mechanical ventilation. However, do not intubate orders (DNI), prevent the use of this treatment in some cases. The aim of this study was to evaluate if non-invasive ventilatory supports can provide a good therapeutic alternative to invasive ventilation in patients with severe COVID-19 infection and a DNI. Data were collected from four centres in three European countries. Patients with severe COVID-19 infection were included. We emulated a hypothetical target trial in which outcomes were compared in patients with a DNI order treated exclusively by non-invasive respiratory support with patients who could be intubated if necessary. We set up a propensity score and an inverse probability of treatment weighting to remove confounding by indication. Four-hundred patients were included: 270 were eligible for intubation and 130 had a DNI order. The adjusted risk ratio for death among patients eligible for intubation was 0.81 (95% CI 0.46 to 1.42). The median length of stay in acute care for survivors was similar between groups (18 (10–31) vs. (19 (13–23.5); p = 0.76). The use of non-invasive respiratory support is a good compromise for patients with severe COVID-19 and a do not intubate order.
Outcomes of Universal Newborn Screening Programs: Systematic Review
Authors: Yoshinaga-Itano Christine , Manchaiah Vinaya , Hunnicutt Cynthia
Published: June 2021

Background: This systematic review examined the outcomes (age of identification and intervention, developmental outcomes, cost-effectiveness, and adverse effects on parents) of universal newborn hearing screening (UNHS) for children with permanent congenital hearing loss (PCHL). Materials and methods: Multiple electronic databases were interrogated in March and April 2020 with further reports identified from article citations and unpublished literature. UNHS reports in English with comparisons of outcomes of infants who were not screened, and infants identified through other hearing screening programs. Results: 30 eligible reports from 14 populations with 7,325,138 infants screened through UNHS from 1616 non-duplicate references were included. UNHS results in a lower age of identification, amplification, and the initiation of early intervention services and better language/literacy development. Better speech perception/production were shown in younger, but not in older, children with early identification after UNHS. No significant findings were found for behavior problems and quality of life. UNHS was found to be cost-effective in terms of savings to society. In addition, no significant parental harm was noted as a result of UNHS. Conclusions: In highly developed countries, significantly better outcomes were found for children identified early through UNHS programs. Early language development predicts later literacy and language development.
Clinical Practice of Photodynamic Therapy Using Talaporfin Sodium for Esophageal Cancer
Authors: Yano Tomonori , Minamide Tatsunori , Takashima Kenji , Nakajo Keiichiro , Kadota Tomohiro , Yoda Yusuke
Published: June 2021

Photodynamic therapy (PDT) using a conventional photosensitizer was approved for esophageal cancer in the early 1990s; however, it was replaced by other conventional treatment modalities in clinical practice because of the high frequency of cutaneous phototoxicity and esophageal stricture after the procedure. The second-generation photosensitizer, talaporfin sodium, which features more rapid clearance from the body, was developed to reduce skin phototoxicity, and talaporfin sodium can be excited at longer-wavelength lights comparing with a conventional photosensitizer. Endoscopic PDT using talaporfin sodium was initially developed for the curative treatment of central-type early lung cancer in Japan, and was approved in the early 2000s. After preclinical experiments, PDT using talaporfin sodium was investigated for patients with local failure after chemoradiotherapy, which was the most serious unmet need in the practice of esophageal cancer. According to the favorable results of a multi-institutional clinical trial, PDT using talaporfin sodium was approved as an endoscopic salvage treatment for patients with local failure after chemoradiotherapy for esophageal cancer. While PDT using talaporfin sodium is gradually spreading in clinical practice, further evaluation at the point of clinical benefit is necessary to determine the importance of PDT in the treatment of esophageal cancer.
Prevalence and Determinants of Mental Health among COPD Patients in a Population-Based Sample in Spain
Authors: Fuentes-Alonso Marta , Lopez-Herranz Marta , López-de-Andrés Ana , Ji Zichen , Jiménez-García Rodrigo , Maestre-Miquel Clara , Zamorano-León José J. , Jimenez-Trujillo Isabel , de Miguel-Diez Javier
Published: June 2021

(1) Background: To assess the prevalence of mental disorders (depression and anxiety), psychological distress, and psychiatric medications consumption among persons suffering from COPD; to compare this prevalence with non-COPD controls and to identify which variables are associated with worse mental health. (2) Methods: This is an epidemiological case-control study. The data were obtained from the Spanish National Health Survey 2017. Subjects were classified as COPD if they reported suffering from COPD and the diagnosis of this condition had been confirmed by a physician. For each case, we selected a non-COPD control matched by sex, age, and province of residence. Conditional logistic regression was used for multivariable analysis. (3) Results: The prevalence of mental disorders (33.9% vs. 17.1%; p < 0.001), psychological distress (35.4% vs. 18.2%; p < 0.001), and psychiatric medications consumption (34.1% vs. 21.9%; p < 0.001) was higher among COPD cases compared with non-COPD controls. After controlling for possible confounding variables, such as comorbid conditions and lifestyles, using multivariable regression, the probability of reporting mental disorders (OR 1.41; 95% CI 1.10–1.82).), psychological distress (OR 1.48; 95% CI 1.12–1.91), and psychiatric medications consumption (OR 1.38 95% CI 1.11–1.71) remained associated with COPD. Among COPD cases, being a woman, poor self-perceived health, more use of health services, and active smoking increased the probability of suffering from mental disorders, psychological distress, and psychiatric medication use. Stroke and chronic pain were the comorbidities more strongly associated with these mental health variables. (4) Conclusions: COPD patients have worse mental health and higher psychological distress and consume more psychiatric medications than non-COPD matched controls. Variables associated with poorer mental health included being a woman, poor self-perceived health, use of health services, and active smoking.
NecroX-5 Can Suppress Melanoma Metastasis by Reducing the Expression of Rho-Family GTPases
Authors: Moon Gue-Tae , Lee Ji-Hyun , Jeong Sang-Hyun , Jin Song-Wan , Park Young-Min
Published: June 2021

NecroX-5 (NX-5) is a cell-permeable necrosis inhibitor with cytoprotective effects. Although it has been reported to inhibit lung and breast cancer metastasis by modulating migration, its therapeutic effect on melanoma metastasis is still unknown. In this study, we examined the anti-metastatic effect of NX-5 on melanoma cell lines and its related therapeutic mechanism. The anti-metastatic effect of NX-5 on melanoma cell lines was determined using a transwell migration assay. We performed a quantitative real-time polymerase chain reaction and western blot analysis to measure changes in the expression of mRNA and protein, respectively, for major mediators of Rho-family GTPases after NX-5 treatment in melanoma cells. In addition, after constructing the 3D melanoma model, the expression of Rho-family GTPases was measured by immunohistochemistry. NX-5 (10 μM and 20 μM) treatment significantly reduced melanoma cell migration (p < 0.01). Additionally, NX-5 (20 μM) treatment significantly decreased the mRNA and protein expression levels of Cdc42, Rac1, and RhoA in melanoma cells compared with the untreated group (p < 0.001 and p < 0.05, respectively). Immunohistochemistry for our 3D melanoma model showed that Cdc42, Rac1, and RhoA were constitutively expressed in the nuclei of melanoma cells of the untreated group, and NX-5 treatment decreased their expression. These results demonstrate that NX-5 can suppress melanoma metastasis by reducing the expression of Rho-family GTPases.
Systematic Review on Optical Diagnosis of Early Gastrointestinal Neoplasia
Authors: Wagner Andrej , Zandanell Stephan , Kiesslich Tobias , Neureiter Daniel , Klieser Eckhard , Holzinger Josef , Berr Frieder
Published: June 2021

Background: Meticulous endoscopic characterization of gastrointestinal neoplasias (GN) is crucial to the clinical outcome. Hereby the indication and type of resection (endoscopically, en-bloc or piece-meal, or surgical resection) are determined. By means of established image-enhanced (IEE) and magnification endoscopy (ME) GN can be characterized in terms of malignancy and invasion depth. In this context, the statistical evidence and accuracy of these diagnostic procedures should be elucidated. Here, we present a systematic review of the literature. Results: 21 Studies could be found which met the inclusion criteria. In clinical prospective trials and meta-analyses, the diagnostic accuracy of >90% for characterization of malignant neoplasms could be documented, if ME with IEE was used in squamous cell esophageal cancer, stomach, or colonic GN. Conclusions: Currently, by means of optical diagnosis, today’s gastrointestinal endoscopy is capable of determining the histological subtype, exact lateral spread, and depth of invasion of a lesion. The prerequisites for this are an exact knowledge of the anatomical structures, the endoscopic classifications based on them, and a systematic learning process, which can be supported by training courses. More prospective clinical studies are required, especially in the field of Barrett’s esophagus and duodenal neoplasia.
Changes in the Allostatic Response to Whole-Body Cryotherapy and Static-Stretching Exercises in Chronic Fatigue Syndrome Patients vs. Healthy Individuals
Authors: Kujawski Sławomir , Bach Anna M. , Słomko Joanna , Pheby Derek F. H. , Murovska Modra , Newton Julia L. , Zalewski Paweł
Published: June 2021

This study represents a comparison of the functional interrelation of fatigue and cognitive, cardiovascular and autonomic nervous systems in a group of Chronic Fatigue Syndrome (CFS) patients compared with those in healthy individuals at different stages of analysis: at baseline and after changes induced by whole-body cryotherapy (WBC) combined with a static-stretching (SS) program. The study included 32 patients (Fukuda criteria) and 18 healthy controls. Fatigue, cognitive, cardiovascular and autonomic function and arterial stiffness were measured before and after 10 sessions of WBC with SS. In the patients, a disturbance in homeostasis was observed. The network relationship based on differences before and after intervention showed comparatively higher stress and eccentricity in the CFS group: 50.9 ± 56.1 vs. 6.35 ± 8.72, p = 0.002, r = 0.28; and 4.8 ± 0.7 vs. 2.4 ± 1, p < 0.001, r = 0.46, respectively. Before and after intervention, in the CFS group increased fatigue was related to baroreceptor function, and baroreceptor function was in turn related to aortic stiffness, but no such relationships were observed in the control group. Differences in the network structure underlying the interrelation among the four measured criteria were observed in both groups, before the intervention and after ten sessions of whole cryotherapy with a static stretching exercise.
Predictors for Perioperative Blood Transfusion in Patients Undergoing Open Cystectomy and Urinary Diversion and Development of a Nomogram: An Observational Cohort Study
Authors: Engel Dominique , Beilstein Christian M. , Jerney Pascal , Furrer Marc A. , Burkhard Fiona C. , Löffel Lukas M. , Wuethrich Patrick Y.
Published: June 2021

Open radical cystectomy is associated with a substantial rate of perioperative blood transfusion. Early detection of potentially modifiable perioperative factors could reduce the need for perioperative blood transfusion and thus positively impact the outcome. We conducted an observational, single-center cohort study of 1168 patients undergoing cystectomy. Perioperative blood transfusion was defined as the need for packed red blood cells and/or fresh frozen plasma units within the first 24 h after the initiation of surgery. Multiple logistic regression analysis was performed to model the association between risk factors and blood transfusion, and a nomogram was developed. Blood transfusion occurred in 370/1168 patients (31.7%). Significant predictors were age (OR: 1.678, (95% CI: 1.379–2.042); p < 0.001), blood loss ratio (6.572, (4.878–8.853); p < 0.001), preoperative hemoglobin (0.316, (0.255–0.391); p < 0.001), tumor stage (2.067, (1.317–3.244); p = 0.002), use of oral anticoagulants (2.70, (1.163–6.270), p = 0.021), and interaction between female sex and blood loss ratio (1.344, (1.011–1.787); p = 0.042). Of the major predictors found to affect perioperative blood transfusion, two can be influenced: blood loss ratio by meticulous surgery and hemoglobin by preoperative optimization. Others such as age or advanced disease are not modifiable. This emphasizes the importance of optimal management of patients prior to surgery.
Health-Related Quality of Life, Depressive Symptoms, Anxiety, and Somatization Symptoms in Male and Female Patients with Chronic Tinnitus
Authors: Boecking Benjamin , Biehl Raphael , Brueggemann Petra , Mazurek Birgit
Published: June 2021

Objective: To investigate the joint impact of tinnitus-related distress (TRD), anxiety, depressive symptoms, and other somatization symptoms on health-related quality of life (HRQoL) in female vs. male patients with chronic tinnitus. Method: Three-hundred-and-fifty-two patients with chronic tinnitus completed audiological testing and a psychological assessment battery that comprised—among other measures—German versions of the Tinnitus Questionnaire, Hospital Anxiety and Depression Scale, Somatic Symptom Scale-8, and Health-Related Quality of Life scale. Descriptive analyses examined associations as well as within- and between-gender differences of the measured variables. Gender-specific serial indirect effects analyses aimed to explain the impact of TRD on HRQoL through psychological processes, notably anxiety, depressive symptoms, and somatization symptoms. Results: Both female and male patients yielded lower mental than physical HRQoL and negative associations between the measured psychological variables and HRQoL. Compared to male patients, female patients reported higher levels of tinnitus-related- and wider psychological distress, other somatization symptoms (e.g., headaches), and impairments in mental and physical HRQoL. For each gender, depressive symptoms, anxiety, and somatization symptoms fully mediated the effect of TRD on mental and physical HRQoL. A double-dissociation revealed an interaction of somatization symptoms and depression on the TRD-HRQoL association in women, and of somatization symptoms and anxiety in men. Conclusions: In patients with chronic tinnitus, psychological constructs account for reported impairments in both mental and physical HRQoL. To improve patients’ HRQoL, treatment conceptualizations should consider gender-specific psychological expressions of low mood or anxiety.
Analysing Complex Oral Protein Samples: Complete Workflow and Case Analysis of Salivary Pellicles
Authors: Wei Chen-Xuan , Burrow Michael Francis , Botelho Michael George , Leung W. Keung
Published: June 2021

Studies on small quantity, highly complex protein samples, such as salivary pellicle, have been enabled by recent major technological and analytical breakthroughs. Advances in mass spectrometry-based computational proteomics such as Multidimensional Protein Identification Technology have allowed precise identification and quantification of complex protein samples on a proteome-wide scale, which has enabled the determination of corresponding genes and cellular functions at the protein level. The latter was achieved via protein-protein interaction mapping with Gene Ontology annotation. In recent years, the application of these technologies has broken various barriers in small-quantity-complex-protein research such as salivary pellicle. This review provides a concise summary of contemporary proteomic techniques contributing to (1) increased complex protein (up to hundreds) identification using minute sample sizes (µg level), (2) precise protein quantification by advanced stable isotope labelling or label-free approaches and (3) the emerging concepts and techniques regarding computational integration, such as the Gene Ontology Consortium and protein-protein interaction mapping. The latter integrates the structural, genomic, and biological context of proteins and genes to predict protein interactions and functional connections in a given biological context. The same technological breakthroughs and computational integration concepts can also be applied to other low-volume oral protein complexes such as gingival crevicular or peri-implant sulcular fluids.
Predictors of Oral Infection by Mucosal and Cutaneous Human Papillomaviruses in HIV-Infected and Uninfected Men Who Have Sex with Men of the OHMAR Study
Authors: Giuliani Massimo , Gheit Tarik , Rollo Francesca , Tommasino Massimo , Latini Alessandra , Benevolo Maria , Pichi Barbara , Pellini Raul , McKay-Chopin Sandrine , Cristaudo Antonio , Giuliani Eugenia , Morrone Aldo , Donà Maria Gabriella
Published: June 2021

Mucosal Human Papillomaviruses (HPVs) play a role in the development of a subset of head and neck cancers. Cutaneous HPVs are abundantly present in the oral cavity. The determinants of these infections have not been extensively investigated. We assessed the correlates of oral infection by alpha and beta and/or gamma HPVs in HIV-infected and uninfected men who have sex with men (MSM). Oral rinse-and-gargles were collected with a mouthwash. Alpha and beta/gamma HPVs were detected using the Linear Array HPV genotyping test and a multiplex PCR combined with Luminex technology, respectively. Multiple logistic regression was performed to identify independent predictors of oral HPV infection. Overall, 193 HIV-uninfected and 117 HIV-infected MSM were enrolled. Among HIV-infected MSM, the only determinant of alpha HPV infection was the number of lifetime oral sex partners (AOR: 8.26, 95% CI: 2.26–30.16). The strongest determinant of beta/gamma HPV infection was represented by practicing condomless receptive oral sex (AOR: 10.76, 95% CI: 1.56–74.17). Age was independently associated with alpha HPV infection in HIV-uninfected MSM. Beta/gamma HPV infection was not associated with sexual behavior in these subjects. In conclusion, predictors of oral infection differ between HIV-infected and uninfected MSM, as well as between alpha and beta/gamma HPVs.
A New Score Unveils a High Prevalence of Mild Cognitive Impairment in Patients with Nonalcoholic Fatty Liver Disease
Authors: Giménez-Garzó Carla , Fiorillo Alessandra , Ballester-Ferré María-Pilar , Gallego Juan-José , Casanova-Ferrer Franc , Urios Amparo , Benlloch Salvador , Martí-Aguado David , San-Miguel Teresa , Tosca Joan , Ríos María-Pilar , Montón Cristina , Durbán Lucía , Escudero-García Desamparados , Aparicio Luis , Felipo Vicente , Montoliu Carmina
Published: June 2021

Patients with nonalcoholic fatty liver disease (NAFLD) may show mild cognitive impairment (MCI). The neurological functions affected remain unclear. The aims were to: (1) Characterize the neuropsychological alterations in NAFLD patients; (2) assess the prevalence of impairment of neurological functions evaluated; (3) develop a new score for sensitive and rapid MCI detection in NAFLD; (4) assess differences in MCI features between patients with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH); and (5) compare neuropsychological alterations in NAFLD patients with cirrhotic patients with MCI. Fifty-nine NAFLD patients and 53 controls performed psychometric tests assessing different neurological functions: PHES (Psychometric Hepatic Encephalopathy Score) battery, d2, Stroop, Oral SDMT (Symbol Digit Modalities Test), Digit Span, number-letter test, and bimanual and visual-motor coordination tests. NAFLD patients show impairment in attention, mental concentration, psychomotor speed, cognitive flexibility, inhibitory mental control, and working memory. We developed a new, rapid, and sensitive score based on the most affected parameters in NAFLD patients, unveiling that 32% of NAFLD show MCI. Prevalence was similar in NAFL (36%) or NASH (27%) patients, but lower in NAFLD than in cirrhosis (65%). MCI prevalence is significant in NAFLD patients. Psychometric testing is warranted in these patients to unveil MCI and take appropriate measures to reverse and prevent its progression.
Cognitive Impairment in People with Diabetes-Related Foot Ulceration
Authors: Siru Ranita , Burkhardt Melanie , Davis Wendy , Hiew Jonathan , Manning Laurens , Ritter Jens , Norman Paul , Makepeace Ashley , Fegan Peter , Bruce David , Davis Timothy , Hamilton Emma
Published: June 2021

Aims: To determine whether there is an excess of cognitive impairment in patients with type 2 diabetes and foot ulceration. Methods: 55 patients with type 2 diabetes and foot ulcers attending Multidisciplinary Diabetes Foot Ulcer clinics (MDFU cohort) were compared with 56 patients with type 2 diabetes attending Complex Diabetes clinics (CDC cohort) using commonly used screening tests for cognitive impairment (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA)), as well as foot self-care, mood and health literacy. MMSE was also compared between the MDFU cohort and a historical community-based cohort of patients with type 2 diabetes (FDS2 cohort). Results: Median MMSE scores were the same in all three groups (28/30). Median MOCA scores did not differ between the MDFU and CDC cohorts (25/30). There were no significant differences in the percentages of patients with MMSE ≤ 24 or MOCA ≤ 25 between MDFU and CDC cohorts (3.6% versus 10.7%, p = 0.27 and 56.4% versus 51.8%, p = 0.71, respectively), findings that did not change after adjustment for age, sex, education, diabetes duration, and random blood glucose. Conclusions: Using conventionally applied instruments, patients with type 2 diabetes and foot ulceration have similar cognition compared with patients without, from either hospital-based clinic or community settings.
Preemptive Duloxetine Relieves Postoperative Pain and Lowers Wound Temperature in Centrally Sensitized Patients Undergoing Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Kim Man Soo , Koh In Jun , Sung Yong Gyu , Park Dong Chul , Na Jae Won , In Yong
Published: June 2021

(1) Background: The purpose of this study was to determine whether preemptive duloxetine in patients with central sensitization (CS) is effective for acute postoperative pain control and wound healing following total knee arthroplasty (TKA). (2) Methods: CS was defined as a score of 40 points or higher on the Central Sensitization Inventory (CSI) survey. Thirty-nine patients with CS were randomly assigned to either the duloxetine group (n = 19) or the placebo group (n = 20). The duloxetine group took duloxetine 30 mg once a day, while the placebo group took the placebo medication once a day. A pain visual analog scale (VAS) and the Brief Pain Inventory (BPI), wound complications, the temperature of the surgical site, and adverse events were investigated. Skin temperature was measured at the center of the patella using a portable digital thermometer. (3) Results: The duloxetine group reported significantly lower pain VAS scores during follow-up periods up to 6 weeks after surgery (all p < 0.05). BPI interference also showed significantly superior results in the duloxetine group after surgery (all p < 0.05). Although there was no difference in the rate of wound complications between the two groups (p > 0.05), the duloxetine group showed significantly lower wound temperature than the placebo group during the follow-up period (all p < 0.05). (4) Conclusion: In this study, preemptive duloxetine effectively reduced pain and lowered wound temperature following TKA in CS patients.