bluuebunny/crossref_metadata_2025 huggingface dataset:
Acquired Nasopharyngeal Stenosis Correction Using a Modified Palatal Flaps Technique in Obstructive Sleep Apnea (OSA) Patients
Authors: Cammaroto Giovanni , Stringa Luigi Marco , Cerritelli Luca , Bianchi Giulia , Meccariello Giuseppe , Gobbi Riccardo , Iannella Giannicola , Magliulo Giuseppe , Zhang Henry , Baghat Ahmed Yassin , Galletti Francesco , Pelucchi Stefano , Stomeo Francesco , Younes Muawya Bani , AlAjmi Mohamed , De Vito Andrea , Vicini Claudio
Published: March 2020

Background: Acquired nasopharyngeal stenosis is a rare and heterogeneous pathological condition that has different causes, generally resulting as a complication of a pharyngeal surgery, especially in patients affected by obstructive sleep apnea (OSA). Different approaches have been proposed for the treatment of nasopharyngeal stenosis but a unique and standardized management has not yet been presented. The aim of our paper is to evaluate the efficacy of our surgical technique, describing its steps and results with the aim to consider it as a possible solution for the treatment of this condition. Methods: This is a retrospective cohort study. Eight patients (mean age 27.25 years old (yo), range 8–67 yo; Male/Female ratio 4/4; mean body mass index (BMI) 26.1) affected by OSA (mean apnea hypopnea index (AHI) before OSA surgery was 22.1) and acquired nasopharyngeal stenosis as a consequence of different pharyngeal surgeries were treated with our modified approach in the Department of Otolaryngology, Morgagni Pierantoni Hospital, Forlì, Italy. Resolution of stenosis and complication rate were the main outcome measures. Results: Complete resolution of the stenosis was achieved in all cases and no complications were recorded at three weeks, six months, and 2 years follow-up. Conclusions: Our technique appears to be a promising method for the management of nasopharyngeal stenosis in OSA patients. However, further studies comparing different techniques and reporting on larger series and longer follow up time are needed to prove the efficacy of the proposed technique.
Cross-Cultural Variation in BMI, Sedentary Behavior, and Physical Activity in International School Girls Residing in Saudi Arabia
Authors: Alhusaini Adel A. , Melam Ganeswara Rao , Buragadda Syamala
Published: March 2020

Background: The current study was done to assess the cross-cultural difference in physical activity and sedentary behavior among girls from culturally, environmentally, and geographically diverse countries residing in Saudi Arabia. Methods: This was a comparative cross-sectional study conducted among expatriate girls (N = 275), aged 9–16 years. Participants were from India (n = 65), Pakistan (n = 88), Egypt (n = 50), Sudan (n = 49), and other nationals (n = 23). They were randomly selected from different schools in Riyadh and their Body Mass Index (BMI) and screen time was assessed. Physical activity (PA) and leisure-time activity was assessed using Physical Activity Questionnaire for Older Children (PAQ-C) and the Godin-Shephard Leisure-Time Exercise Questionnaire (GSLTPAQ) respectively. Results: Out of 275, 65.8% were active and 34.2% were insufficiently active as per the GSLTPAQ, and half of them were moderately active and only 22.2% were extremely active as per PAQ-C. No statistical significant differences in their BMI status, screen time, or the levels of PA among expatriate girls. Conclusions: This study shows that the expatriate female school children in Saudi Arabia demonstrated a similar pattern in their BMI, sedentary time spent, and PA levels.
Socioeconomic Differences in Occupational Health Service Utilization and Sickness Absence Due to Mental Disorders: A Register-Based Retrospective Cohort Study
Authors: Harkko Jaakko , Sumanen Hilla , Pietiläinen Olli , Piha Kustaa , Mänty Minna , Lallukka Tea , Rahkonen Ossi , Kouvonen Anne
Published: March 2020

Occupational health service (OHS) is the main provider of primary care services for the working population in Finland. We investigated whether socioeconomic differences in the utilization of OHS predict sickness absence (SA) due to mental disorders. We used register linkage data covering the employees of the City of Helsinki aged 18–34 years (N = 6545) and 35–54 years (N = 15,296) from 2009 to 2014. The outcome was medically certified long-term (over 11 days) SA due to mental disorders. Cox regression analyses were performed to obtain hazard ratios (HR) and their 95% confidence intervals (CIs). Employees with low socioeconomic position (SEP) used OHS more frequently. The number of OHS visits independently predicted SA due to mental disorders. HRs were 1.59 (95% CI 1.35, 1.86) for those with frequent visits and 1.73 (95% CI 1.30, 2.29) for those with a clustered visit pattern among 18–34 year old employees; and 1.46 (95% CI 1.18, 1.81) and 1.41 (95% CI 1.14, 1.74) among 35–54 year old employees, respectively. In both age groups, lower education and routine non-manual worker position indicated the highest probability of SA. Low SEP predicts both high OHS utilization and subsequent SA due to mental disorders. Medical records may be used to accurately predict future SA, and the results indicate that preventive measures should be targeted particularly to younger employees with lower SEP.
Atlanta Residents’ Knowledge Regarding Heavy Metal Exposures and Remediation in Urban Agriculture
Authors: Balotin Lauren , Distler Samantha , Williams Antoinette , Peters Samuel J.W. , Hunter Candis M. , Theal Chris , Frank Gil , Alvarado Taranji , Hernandez Rosario , Hines Arthur , Saikawa Eri
Published: March 2020

Urban agriculture and gardening provide many health benefits, but the soil is sometimes at risk of heavy metal and metalloid (HMM) contamination. HMM, such as lead and arsenic, can result in adverse health effects for humans. Gardeners may face exposure to these contaminants because of their regular contact with soil and consumption of produce grown in urban areas. However, there is a lack of research regarding whether differential exposure to HMM may be attributed to differential knowledge of exposure sources. In 2018, industrial slag and hazardous levels of soil contamination were detected in West Atlanta. We conducted community-engaged research through surveys and follow-up interviews to understand awareness of slag, HMM in soil, and potential remediation options. Home gardeners were more likely to recognize HMM health effects and to cite health as a significant benefit of gardening than community gardeners. In terms of knowledge, participants were concerned about the potential health effects of contaminants in soil yet unconcerned with produce in their gardens. Gardeners’ knowledge on sources of HMM exposure and methods for remediation were low and varied based on racial group.
Gender-Related Differences in Flood Risk Perception and Behaviours among Private Groundwater Users in the Republic of Ireland
Authors: McDowell Cillian P. , Andrade Luisa , O’Neill Eoin , O’Malley Kevin , O’Dwyer Jean , Hynds Paul D.
Published: March 2020

Extreme weather events including flooding can have severe personal, infrastructural, and economic consequences, with recent evidence pointing to surface flooding as a pathway for the microbial contamination of private groundwater supplies. There is a pressing need for increasingly focused information and awareness campaigns to highlight the risks posed by extreme weather events and appropriate subsequent post-event actions. To date, little is known about the presence, directionality or magnitude of gender-related differences regarding flood risk awareness and behaviour among private groundwater users, a particularly susceptible sub-population due to an overarching paucity of infrastructural regulation across many regions. The current study investigated gender-related differences in flood risk perception and associated mitigation behaviours via a cross-sectional, national survey of 405 (168 female, 237 male) private groundwater supply users. The developed survey instrument assessed socio-demographic profile, previous flood experience, experiential and conjectural health behaviours (contingent on previous experience), and Risk, Attitude, Norms, Ability, Self-regulation (RANAS) framework questions. Statistically significant gender differences were found between both ‘Norm—Descriptive’ and ‘Ability—Self-efficacy’ RANAS elements (p < 0.05). Female respondents reported a lower level of awareness of the need for post-flood action(s) (8.9% vs. 16.5%), alongside a perceived “lack of information” as a reason for not testing their domestic well (4.9% vs. 11.5%). Conversely, male respondents were more likely to report awareness of their well location in relation to possible contamination sources (96.6% vs. 89.9%) and awareness of previous water testing results (98.9% vs. 93.0%). Gender-related gaps exist within the studied private groundwater reliant cohort, a sub-population which has to date remained under-studied within the context of climate change and extreme weather events. Accordingly, findings suggest that gender-focused communication and education may represent an effective tool for protecting current and future generations of global groundwater users.
Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies
Authors: Medina Mauricio A. , Oza Goldie , Sharma Ashutosh , Arriaga L.G. , Hernández Hernández José Manuel , Rotello Vincent M. , Ramirez Jose Tapia
Published: March 2020

Triple-negative breast cancer (TNBC) cells are deficient in estrogen, progesterone and ERBB2 receptor expression, presenting a particularly challenging therapeutic target due to their highly invasive nature and relatively low response to therapeutics. There is an absence of specific treatment strategies for this tumor subgroup, and hence TNBC is managed with conventional therapeutics, often leading to systemic relapse. In terms of histology and transcription profile these cancers have similarities to BRCA-1-linked breast cancers, and it is hypothesized that BRCA1 pathway is non-functional in this type of breast cancer. In this review article, we discuss the different receptors expressed by TNBC as well as the diversity of different signaling pathways targeted by TNBC therapeutics, for example, Notch, Hedgehog, Wnt/b-Catenin as well as TGF-beta signaling pathways. Additionally, many epidermal growth factor receptor (EGFR), poly (ADP-ribose) polymerase (PARP) and mammalian target of rapamycin (mTOR) inhibitors effectively inhibit the TNBCs, but they face challenges of either resistance to drugs or relapse. The resistance of TNBC to conventional therapeutic agents has helped in the advancement of advanced TNBC therapeutic approaches including hyperthermia, photodynamic therapy, as well as nanomedicine-based targeted therapeutics of drugs, miRNA, siRNA, and aptamers, which will also be discussed. Artificial intelligence is another tool that is presented to enhance the diagnosis of TNBC.
Insight Into the Formation Paths of Methyl Bromide From Syringic Acid in Aqueous Bromide Solutions Under Simulated Sunlight Irradiation
Authors: Liu Hui , Tong Tong , Pu Yingying , Sun Bing , Zhu Xiaomei , Yan Zhiyu
Published: March 2020

Methyl bromide (CH3Br) is one of the largest natural sources of bromine in the stratosphere, where it leads to ozone depletion. This paper reported the photochemical production of CH3Br from syringic acid (SA) that has been used as an environmentally relevant model compound for terrestrially-derived dissolved organic matter. The formation of CH3Br increased with the increase of bromide ion concentration ranging from 0.8 to 80 mmol L−1. Ferric ions (Fe(III)) enhanced CH3Br production, while chloride inhibited it, with or without Fe(III). Meanwhile, methyl chloride (CH3Cl) was generated in the presence of chloride and was inhibited by Fe(III). The different effects of Fe(III) on the formation of CH3Cl and CH3Br indicate their diverse formation paths. Based on the intermediates identified by liquid chromatography-mass spectrometry and the confirmation of the formation of Fe(III)-SA complexes, it was proposed that there were two formation paths of CH3Br from SA in the bromide-enriched water under simulated sunlight irradiation. One path was via nucleophilic attack of Br− on the excited state protonation of SA; the other was via the combination of methyl radical and bromine radical when Fe(III) was present. This work suggests that the photochemical formation of CH3Br may act as a potential natural source of CH3Br in the bromide-enriched environmental matrix, and helps in better understanding the formation mechanism of CH3Br.
Brain Sex Differences Related to Gender Identity Development: Genes or Hormones?
Authors: Ristori Jiska , Cocchetti Carlotta , Romani Alessia , Mazzoli Francesca , Vignozzi Linda , Maggi Mario , Fisher Alessandra Daphne
Published: March 2020

The complex process of sexual differentiation is known to be influenced by biological and environmental determinants. The present review has the aim of summarizing the most relevant studies on the biological basis of sexual development, and in particular, it focuses on the impact of sex hormones and genetic background on the development of sexual differentiation and gender identity. The authors conducted a search of published studies on Medline (from January 1948 to December 2019). The evidence suggests that the sexual dimorphic brain could be the anatomical substrate of psychosexual development, on which gonadal hormones may have a shaping role during prenatal and pubertal periods. Additionally, according to several heritability studies, genetic components may have a role, but a promising candidate gene has not been identified. Even though growing evidence underlines the primary role of biological factors on psychosexual development, further studies are necessary to better explain their complex interactions.
Influence of Salt Stress on Growth of Spermosphere Bacterial Communities in Different Peanut (Arachis hypogaea L.) Cultivars
Authors: Xu Yang , Zhang Dai , Dai Liangxiang , Ding Hong , Ci Dunwei , Qin Feifei , Zhang Guanchu , Zhang Zhimeng
Published: March 2020

Background: Exposure of seeds to high salinity can cause reduced germination and poor seedling establishment. Improving the salt tolerance of peanut (Arachis hypogaea L.) seeds during germination is an important breeding goal of the peanut industry. Bacterial communities in the spermosphere soils may be of special importance to seed germination under salt stress, whereas extant results in oilseed crop peanut are scarce. Methods: Here, bacterial communities colonizing peanut seeds with salt stress were characterized using 16S rRNA gene sequencing. Results: Peanut spermosphere was composed of four dominant genera: Bacillus, Massilia, Pseudarthrobacter, and Sphingomonas. Comparisons of bacterial community structure revealed that the beneficial bacteria (Bacillus), which can produce specific phosphatases to sequentially mineralize organic phosphorus into inorganic phosphorus, occurred in relatively higher abundance in salt-treated spermosphere soils. Further soil enzyme activity assays showed that phosphatase activity increased in salt-treated spermosphere soils, which may be associated with the shift of Bacillus. Conclusion: This study will form the foundation for future improvement of salt tolerance of peanuts at the seed germination stage via modification of the soil microbes.
Tyrosine–Chlorambucil Conjugates Facilitate Cellular Uptake through L-Type Amino Acid Transporter 1 (LAT1) in Human Breast Cancer Cell Line MCF-7
Authors: Pocasap Piman , Weerapreeyakul Natthida , Timonen Juri , Järvinen Juulia , Leppänen Jukka , Kärkkäinen Jussi , Rautio Jarkko
Published: March 2020

l-type amino acid transporter 1 (LAT1) is an amino acid transporter that is overexpressed in several types of cancer and, thus, it can be a potential target for chemotherapy. The objectives of this study were to (a) synthesize LAT1-targeted chlorambucil derivatives and (b) evaluate their LAT1-mediated cellular uptake as well as antiproliferative activity in vitro in the human breast cancer MCF-7 cell line. Chlorambucil was conjugated to l-tyrosine—an endogenous LAT1 substrate—via either ester or amide linkage (compounds 1 and 2, respectively). While chlorambucil itself did not bind to LAT1, its derivatives 1 and 2 bound to LAT1 with a similar affinity as with l-tyrosine and their respective cellular uptake was significantly higher than that of chlorambucil in MCF-7. The results of our cellular uptake study are indicative of antiproliferative activity, as a higher intracellular uptake of chlorambucil derivatives resulted in greater cytotoxicity than chlorambucil by itself. LAT1 thus contributes to intracellular uptake of chlorambucil derivatives and, therefore, increases antiproliferative activity. The understanding gained from our research can be used in the development of LAT1-targeted anticancer drugs and prodrugs for site-selective and enhanced chemotherapeutic activity.
Pioglitazone and Deoxyribonucleoside Combination Treatment Increases Mitochondrial Respiratory Capacity in m.3243A>G MELAS Cybrid Cells
Authors: Burgin Harrison J. , Lopez Sanchez M. Isabel G. , Smith Craig M. , Trounce Ian A. , McKenzie Matthew
Published: March 2020

The lack of effective treatments for mitochondrial disease has seen the development of new approaches, including those that aim to stimulate mitochondrial biogenesis to boost ATP generation above a critical disease threshold. Here, we examine the effects of the peroxisome proliferator-activated receptor γ (PPARγ) activator pioglitazone (PioG), in combination with deoxyribonucleosides (dNs), on mitochondrial biogenesis in cybrid cells containing >90% of the m.3243A>G mutation associated with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). PioG + dNs combination treatment increased mtDNA copy number and mitochondrial mass in both control (CON) and m.3243A>G (MUT) cybrids, with no adverse effects on cell proliferation. PioG + dNs also increased mtDNA-encoded transcripts in CON cybrids, but had the opposite effect in MUT cybrids, reducing the already elevated transcript levels. Steady-state levels of mature oxidative phosphorylation (OXPHOS) protein complexes were increased by PioG + dNs treatment in CON cybrids, but were unchanged in MUT cybrids. However, treatment was able to significantly increase maximal mitochondrial oxygen consumption rates and cell respiratory control ratios in both CON and MUT cybrids. Overall, these findings highlight the ability of PioG + dNs to improve mitochondrial respiratory function in cybrid cells containing the m.3243A>G MELAS mutation, as well as their potential for development into novel therapies to treat mitochondrial disease.
Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration
Authors: Herzog David P. , Mellema Ratnadevi M. , Remmers Floortje , Lutz Beat , Müller Marianne B. , Treccani Giulia
Published: March 2020

Background: Rapid-acting antidepressants ketamine and (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) have overcome some of the major limitations of classical antidepressants. However, little is known about sex-specific differences in the behavioral and molecular effects of ketamine and (2R,6R)-HNK in rodents. Methods: We treated mice with an intraperitoneal injection of either saline, ketamine (30 mg kg−1) or (2R,6R)-HNK (10 mg kg−1). We performed a comprehensive behavioral test battery to characterize the Arc-CreERT2 × CAG-Sun1/sfGFP mouse line which enables targeted recombination in active populations. We performed a molecular study in Arc-CreERT2 × CAG-Sun1/sfGFP female mice using both immunohistochemistry and in situ hybridization. Results: Arc-CreERT2 × CAG-Sun1/sfGFP mice showed sex differences in sociability and anxiety tests. Moreover, ketamine and (2R,6R)-HNK had opposite effects in the forced swim test (FST) depending on gender. In addition, in male mice, ketamine-treated animals were less immobile compared to (2R,6R)-HNK, thus showing a different profile of the two drugs in the FST. At the molecular level we identified Bdnf mRNA level to be increased after ketamine treatment in female mice. Conclusion: Arc-CreERT2 × CAG-Sun1/sfGFP mice showed sex differences in social and anxiety behavior and a different pattern between ketamine and (2R,6R)-HNK in the FST in male and female mice. At the molecular level, female mice treated with ketamine showed an increase of Bdnf mRNA level, as previously observed in male mice.
Role of uL3 in the Crosstalk between Nucleolar Stress and Autophagy in Colon Cancer Cells
Authors: Pecoraro Annalisa , Carotenuto Pietro , Franco Brunella , De Cegli Rossella , Russo Giulia , Russo Annapina
Published: March 2020

The nucleolus is the site of ribosome biogenesis and has been recently described as important sensor for a variety of cellular stressors. In the last two decades, it has been largely demonstrated that many chemotherapeutics act by inhibiting early or late rRNA processing steps with consequent alteration of ribosome biogenesis and activation of nucleolar stress response. The overall result is cell cycle arrest and/or apoptotic cell death of cancer cells. Our previously data demonstrated that ribosomal protein uL3 is a key sensor of nucleolar stress activated by common chemotherapeutic agents in cancer cells lacking p53. We have also demonstrated that uL3 status is associated to chemoresistance; down-regulation of uL3 makes some chemotherapeutic drugs ineffective. Here, we demonstrate that in colon cancer cells, the uL3 status affects rRNA synthesis and processing with consequent activation of uL3-mediated nucleolar stress pathway. Transcriptome analysis of HCT 116p53−/− cells expressing uL3 and of a cell sub line stably depleted of uL3 treated with Actinomycin D suggests a new extra-ribosomal role of uL3 in the regulation of autophagic process. By using confocal microscopy and Western blotting experiments, we demonstrated that uL3 acts as inhibitory factor of autophagic process; the absence of uL3 is associated to increase of autophagic flux and to chemoresistance. Furthermore, experiments conducted in presence of chloroquine, a known inhibitor of autophagy, indicate a role of uL3 in chloroquine-mediated inhibition of autophagy. On the basis of these results and our previous findings, we hypothesize that the absence of uL3 in cancer cells might inhibit cancer cell response to drug treatment through the activation of cytoprotective autophagy. The restoration of uL3 could enhance the activity of many drugs thanks to its pro-apoptotic and anti-autophagic activity.
Modulation of NLRP3 Inflammasome through Formyl Peptide Receptor 1 (Fpr-1) Pathway as a New Therapeutic Target in Bronchiolitis Obliterans Syndrome
Authors: D’Amico Ramona , Fusco Roberta , Cordaro Marika , Siracusa Rosalba , Peritore Alessio Filippo , Gugliandolo Enrico , Crupi Rosalia , Scuto Maria , Cuzzocrea Salvatore , Di Paola Rosanna , Impellizzeri Daniela
Published: March 2020

Chronic rejection is the major leading cause of morbidity and mortality after lung transplantation. Bronchiolitis obliterans syndrome (BOS), a fibroproliferative disorder of the small airways, is the main manifestation of chronic lung allograft rejection. We investigated, using transgenic mice, the mechanisms through which the deficiency of IL-1β/IL-18, Casp-1, or Fpr-1 genes could be protective in an experimental model of BOS, induced in mice by allogeneic heterotopic tracheal transplantation. Fpr-1 KO mice showed a marked reduction in histological markers of BOS and of mast cell numbers compared to other groups. Molecular analyses indicated that the absence of the Fpr-1 gene was able to decrease NF-κB nuclear translocation and modulate NLRP3 inflammasome signaling and the mitogen-activated protein kinase (MAPK) pathway in a more significant way compared to other groups. Additionally, Fpr-1 gene deletion caused a reduction in resistance to the apoptosis, assessed by the TUNEL assay. Immunohistochemical analyses indicated changes in nitrotyrosine, PARP, VEGF, and TGF-β expression associated with the pathology, which were reduced in the absence of the Fpr1 gene more so than by the deletion of IL-1β/IL-18 and Casp-1. We underline the importance of the NLRP3 inflammasome and the pathogenic role of Fpr-1 in experimental models of BOS, which is the result of the modulation of immune cell recruitment together with the modulation of local cellular activation, suggesting this gene as a new target in the control of the pathologic features of BOS.
Neuroimaging Biomarkers for Predicting Treatment Response and Recurrence of Major Depressive Disorder
Authors: Kang Seung-Gul , Cho Seo-Eun
Published: March 2020

The acute treatment duration for major depressive disorder (MDD) is 8 weeks or more. Treatment of patients with MDD without predictors of treatment response and future recurrence presents challenges and clinical problems to patients and physicians. Recently, many neuroimaging studies have been published on biomarkers for treatment response and recurrence of MDD using various methods such as brain volumetric magnetic resonance imaging (MRI), functional MRI (resting-state and affective tasks), diffusion tensor imaging, magnetic resonance spectroscopy, near-infrared spectroscopy, and molecular imaging (i.e., positron emission tomography and single photon emission computed tomography). The results have been inconsistent, and we hypothesize that this could be due to small sample size; different study design, including eligibility criteria; and differences in the imaging and analysis techniques. In the future, we suggest a more sophisticated research design, larger sample size, and a more comprehensive integration including genetics to establish biomarkers for the prediction of treatment response and recurrence of MDD.
Biosurfactants: Eco-Friendly and Innovative Biocides against Biocorrosion
Authors: Płaza Grażyna , Achal Varenyam
Published: March 2020

Corrosion influenced by microbes, commonly known as microbiologically induced corrosion (MIC), is associated with biofilm, which has been one of the problems in the industry. The damages of industrial equipment or infrastructures due to corrosion lead to large economic and environmental problems. Synthetic chemical biocides are now commonly used to prevent corrosion, but most of them are not effective against the biofilms, and they are toxic and not degradable. Biocides easily kill corrosive bacteria, which are as the planktonic and sessile population, but they are not effective against biofilm. New antimicrobial and eco-friendly substances are now being developed. Biosurfactants are proved to be one of the best eco-friendly anticorrosion substances to inhibit the biocorrosion process and protect materials against corrosion. Biosurfactants have recently became one of the important products of bioeconomy with multiplying applications, while there is scare knowledge on their using in biocorrosion treatment. In this review, the recent findings on the application of biosurfactants as eco-friendly and innovative biocides against biocorrosion are highlighted.
A Cross-Sectional Study Evaluating the Effects of Resistance Exercise on Inflammation and Neurotrophic Factors in Elderly Women with Obesity
Authors: Roh Hee-Tae , Cho Su-Youn , So Wi-Young
Published: March 2020

Purpose: Aging lowers brain functionality, and obesity accelerates this process. Resistance exercise can help reverse aging; however, studies examining how it affects brain function and body mass are limited. Thus, this study aimed to investigate the effect of resistance exercise on inflammation and neurotrophic factors in elderly women with obesity. Methods: Twenty-six elderly women with obesity were selected for this study and randomly assigned into a control group (CG, n = 13) and an experimental group (EG, n = 13). The EG performed resistance training thrice weekly for 12 weeks using elastic bands, while the CG did not exercise. Serum lipid profile (total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)) and nuclear factor Kappa B (NF-κB), interferon-gamma (IFN-γ), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and eotaxin-1 levels were analyzed before and after the intervention. Body composition (soft lean mass (SLM), skeletal muscle mass (SMM), body fat mass (BFM), percent body fat (PBF), waist-hip-ratio (WHR), basal metabolic rates (BMR)) measurements and blood tests were performed. Results: Among the body composition variables, SLM, SMM, and BMR in the EG were significantly increased after intervention (p < 0.05). Serum lipid profile was not significantly different after intervention (p > 0.05). After intervention, the levels of NF-κB, IFN-γ, and eotaxin-1 were significantly lower and BDNF and VEGF were significantly higher in the EG than in the CG (p < 0.05 for all). Conclusions: These results imply that regular resistance training in elderly women with obesity can increase muscle mass, reduce inflammation, and stimulate neurotrophic factors.
Enhanced Antioxidative Defense by Vitamins C and E Consumption Prevents 7-Day High-Salt Diet-Induced Microvascular Endothelial Function Impairment in Young Healthy Individuals
Authors: Barić Lidija , Drenjančević Ines , Mihalj Martina , Matić Anita , Stupin Marko , Kolar Luka , Mihaljević Zrinka , Mrakovčić-Šutić Ines , Šerić Vatroslav , Stupin Ana
Published: March 2020

This study aimed to examine whether the oral supplementation of vitamins C and E during a seven-day high salt diet (HS; ~14 g salt/day) prevents microvascular endothelial function impairment and changes oxidative status caused by HS diet in 51 (26 women and 25 men) young healthy individuals. Laser Doppler flowmetry measurements demonstrated that skin post-occlusive reactive hyperemia (PORH), and acetylcholine-induced dilation (AChID) were significantly impaired in the HS group, but not in HS+C+E group, while sodium nitroprusside-induced dilation remained unaffected by treatments. Serum oxidative stress markers: Thiobarbituric acid reactive substances (TBARS), 8-iso prostaglandin-F2α, and leukocytes’ intracellular hydrogen peroxide (H2O2) production were significantly increased, while ferric-reducing ability of plasma (FRAP) and catalase concentrations were decreased in the HS group. All these parameters remained unaffected by vitamins supplementation. Matrix metalloproteinase 9, antioxidant enzymes Cu/Zn SOD and glutathione peroxidase 1, and leukocytes’ intracellular superoxide production remained unchanged after the protocols in both HS and HS+C+E groups. Importantly, multiple regression analysis revealed that FRAP was the most powerful predictor of AChID, while PORH was strongly predicted by both FRAP and renin-angiotensin system activity. Hereby, we demonstrated that oxidative dis-balance has the pivotal role in HS diet-induced impairment of endothelial and microvascular function in healthy individuals which could be prevented by antioxidative vitamins consumption.
An Ethnic Comparison of Arginine Dimethylation and Cardiometabolic Factors in Healthy Black and White Youth: The ASOS and African-PREDICT Studies
Authors: Bollenbach Alexander , Schutte Aletta E. , Kruger Ruan , Tsikas Dimitrios
Published: March 2020

Proteinic arginine dimethylation (PADiMe) is a major post-translational modification. Proteolysis of asymmetric and symmetric PADiMe products releases asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), respectively, two endogenous atherogenic substances. SDMA, ADMA, and its major metabolite dimethylamine (DMA) are eliminated by the kidney. The urinary concentrations of DMA+ADMA, SDMA, and DMA+ADMA+SDMA are useful measures of the whole-body asymmetric and symmetric PADiMe, respectively. Urinary (DMA+ADMA)/SDMA is an index of the asymmetric to symmetric PADiMe balance. In two bi-ethnic studies, the ASOS (39 black boys, 41 white boys) and the African-PREDICT (292 black young men, 281 white young men) studies, we investigated whether ethnicity is a major determinant of PADiMe, and whether PADiMe is associated with blood pressure and ethnicity-dependent growth and inflammatory factors, including HDL. DMA, ADMA, and SDMA were measured in spot urine samples by gas chromatography–mass spectrometry, and their excretion was corrected for creatinine excretion. In black boys, creatinine-corrected DMA, DMA+ADMA, and DMA+ADMA+SDMA concentrations were lower by 11.7%, 9.5%, and 7.6% (all p < 0.05), respectively, compared to the white boys, and 3.4%, 2.0%, and 1.8% lower (all p < 0.05), respectively, in black compared to white men. (DMA+ADMA)/SDMA did not differ between black boys and black men, but was higher in white boys compared to white men. ADMA did not differ between black and white boys, or between black and white men. Creatinine-corrected SDMA excretion was lower in black boys compared to white boys (by 8%) and to white men (by 3.1%). None of the PADiMe indices were associated with blood pressure in either study. IGF-binding protein 3 correlated inversely with all PADiMe indices in the black men only. Our study showed that asymmetric proteinic arginine dimethylation is higher in white boys than in black boys, and that this difference disappears in adulthood. ADMA metabolism and SDMA excretion were lower in the black subjects compared to the white subjects, suggesting ethnicity-dependent hepatic and renal elimination of ADMA and SDMA in the childhood. The results of our study may have clinical relevance beyond atherosclerosis, such as in growth and inflammation, which have not been sufficiently addressed thus far.
The Treatment of Ingrown Nail: Chemical Matricectomy With Phenol Versus Aesthetic Reconstruction. A Single Blinded Randomized Clinical Trial
Authors: Muriel-Sánchez Juan Manuel , Becerro-de-Bengoa-Vallejo Ricardo , Montaño-Jiménez Pedro , Coheña-Jiménez Manuel
Published: March 2020

Background: In onychocryptosis surgery, incisional and non-incisional matricectomy is indicated according to the stage. The chemical matricectomy with 88% phenol solution is the gold standard and a wedge resection is indicated for more advanced stages. The aesthetic reconstruction has the advantages of the incisional procedure without eponychium incisions and an effectiveness similar to the chemical matricectomy with phenol. Objective: To compare the recurrence and the healing time between the chemical matricectomy with phenol and the aesthetic reconstruction. Methods: A comparative, prospective, parallel, randomized, and one-blinded clinical trial was registered with the European Clinical Trials Database (EudraCT) with identification number 2019-001294-80. Thrity-four patients (56 feet) with 112 onychocryptosis were randomized in two groups. Thirty-six were treated with chemical matricectomy with phenol and 76 with aesthetic reconstruction. Each patient was blind to the surgical procedure assigned by the investigator. The primary outcome measurements were healing time and recurrence. The secondary outcome measurements were post-surgical bleeding, pain, inflammation, and infection rate. Results: The aesthetic reconstruction procedure presents a shorter healing time (8.2 ± 1.4 days vs. 21.3 ± 3.1 days; p < 0.001) with a similar recurrence rate (p = 0.98). Post-operatory bleeding, pain, inflammation, and the infection rate did not show significant differences (p > 0.05). Conclusions: The aesthetic reconstruction presents a shorter healing time, favoring the patients’ recuperation, with a recurrence similar to the chemical matricectomy with 88% phenol solution.
Ischemia-Reperfusion Injury in Marginal Liver Grafts and the Role of Hypothermic Machine Perfusion: Molecular Mechanisms and Clinical Implications
Authors: Czigany Zoltan , Lurje Isabella , Schmelzle Moritz , Schöning Wenzel , Öllinger Robert , Raschzok Nathanael , Sauer Igor M. , Tacke Frank , Strnad Pavel , Trautwein Christian , Neumann Ulf Peter , Fronek Jiri , Mehrabi Arianeb , Pratschke Johann , Schlegel Andrea , Lurje Georg
Published: March 2020

Ischemia-reperfusion injury (IRI) constitutes a significant source of morbidity and mortality after orthotopic liver transplantation (OLT). The allograft is metabolically impaired during warm and cold ischemia and is further damaged by a paradox reperfusion injury after revascularization and reoxygenation. Short-term and long-term complications including post-reperfusion syndrome, delayed graft function, and immune activation have been associated with IRI. Due to the current critical organ shortage, extended criteria grafts are increasingly considered for transplantation, however, with an elevated risk to develop significant features of IRI. In recent years, ex vivo machine perfusion (MP) of the donor liver has witnessed significant advancements. Here, we describe the concept of hypothermic (oxygenated) machine perfusion (HMP/HOPE) approaches and highlight which allografts may benefit from this technology. This review also summarizes clinical applications and the main aspects of ongoing randomized controlled trials on hypothermic perfusion. The mechanistic aspects of IRI and hypothermic MP—which include tissue energy replenishment, optimization of mitochondrial function, and the reduction of oxidative and inflammatory damage following reperfusion—will be comprehensively discussed within the context of current preclinical and clinical evidence. Finally, we highlight novel trends and future perspectives in the field of hypothermic MP in the context of recent findings of basic and translational research.
High Risk of Sustained Ventricular Arrhythmia Recurrence After Acute Myocarditis
Authors: Rosier Laurent , Zouaghi Amir , Barré Valentin , Martins Raphaël , Probst Vincent , Marijon Eloi , Sadoul Nicolas , Chauveau Samuel , Da Costa Antoine , Badoz Marc , Peyrol Michael , Barraud Jérémie , Massoullie Grégoire , Eschalier Romain , Espinosa Madeline , Lesaffre François , Garcia Rodrigue , Degand Bruno , Noël Antoine , Mansourati Jacques , Extramiana Fabrice , Algalarrondo Vincent , Devilliers Hervé , Cottin Yves , Gandjbakhch Estelle , Guenancia Charles
Published: March 2020

Acute myocarditis is associated with cardiac arrhythmia in 25% of cases; a third of these arrhythmias are ventricular tachycardia (VT) or ventricular fibrillation (VF). The implantation of a cardiac defibrillator (ICD) following sustained ventricular arrhythmia remains controversial in these patients. We sought to assess the risk of major arrhythmic ventricular events (MAEs) over time in patients implanted with an ICD following sustained VT/VF in the acute phase of myocarditis compared to those implanted for VT/VF occurring on myocarditis sequelae. Our retrospective observational study included patients implanted with an ICD following VT/VF during acute myocarditis or VT/VF on myocarditis sequelae, from 2007 to 2017, in 15 French university hospitals. Over a median follow-up period of 3 years, MAE occurred in 11 (39%) patients of the acute myocarditis group and 24 (60%) patients of the myocarditis sequelae group. Kaplan–Meier MAE rate estimates at one and three years of follow-up were 19% and 45% in the acute group, and 43% and 64% in the sequelae group. Patients who experienced sustained ventricular arrhythmias during acute myocarditis had a very high risk of VT/VF recurrence during follow-up. These results show that the risk of MAE recurrence remains high after resolution of the acute episode.
Pentraxin 3 (PTX3): A Molecular Marker of Endothelial Dysfunction in Chronic Migraine
Authors: Domínguez-Vivero Clara , Leira Yago , López-Ferreiro Ana , Saavedra Marta , Rodríguez-Osorio Xiana , Sobrino Tomás , Campos Francisco , Castillo José , Leira Rogelio
Published: March 2020

Even though endothelial dysfunction is known to play a role in migraine pathophysiology, studies regarding levels of endothelial biomarkers in migraine have controversial results. Our aim was to evaluate the role of pentraxin 3 (PTX3) and soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) as potential biomarkers of endothelial dysfunction in chronic migraine (CM). We performed a case-control study including 102 CM patients and 28 control subjects and measured serum levels of markers of endothelial dysfunction (PTX3 and sTWEAK) and inflammation [high-sensitivity C-reactive protein (hs-CRP)] as well as brachial artery flow-mediated dilation (FMD) during interictal periods. Interictal serum levels of PTX3 and sTWEAK were higher in CM patients than in controls (1350.6 ± 54.8 versus 476.1 ± 49.4 pg/mL, p < 0.001 and 255.7 ± 21.1 versus 26.4 ± 2.6 pg/mL, p < 0.0001; respectively). FMD was diminished in CM patients compared to controls (9.6 ± 0.6 versus 15.2 ± 0.9%, p < 0.001). Both PTX3 and sTWEAK were negatively correlated with FMD (r = −0.508, p < 0.001 and r = −0.188, p = 0.033; respectively). After adjustment of confounders, PTX3 remained significantly correlated to FMD (r = −0.250, p = 0.013). Diagnosis of CM was 68.4 times more likely in an individual with levels of PTX3 ≥ 832.5 pg/mL, suggesting that PTX3 could be a novel biomarker of endothelial dysfunction in CM.
Biphasic Temporal Relationship between Cancers and Systemic Sclerosis: A Clinical Series from Montpellier University Hospital and Review of the Literature
Authors: Partouche Léo , Goulabchand Radjiv , Maria Alexandre Thibault Jacques , Rivière Sophie , Jorgensen Christian , Rigau Valérie , Bourgier Céline , Bessis Didier , Le Quellec Alain , Quere Isabelle , Morel Jacques , Guilpain Philippe
Published: March 2020

Cancer among patients with systemic sclerosis (SSc) would appear to be more prevalent than in the general population. Pathophysiological hypotheses are multiple, involving intertwined factors such as immune system antitumoral response, oxygen species dysregulation, and immunosuppressive treatments. We aimed to identify SSc patients with cancer monitored at our center, describing their clinical and immunological characteristics, such as cancer-specific outcomes. We focused in particular on the temporal relationships between cancer onset and SSc diagnosis. A retrospective study was conducted on SSc patients from Montpellier University Hospital from 2003 to 2018. Clinical characteristics and outcomes of each SSc patient with cancer were recorded. Fifty-five patients with SSc and at least one cancer was included (median age 56 years (47–66)), with a median follow-up time of 11 years (4–15). Sixty-four metachronous malignancies were identified (12 patients had two cancers). Among them, early-onset cancer occurrences (±5 years from SSc diagnosis) included 23 cancers (39% breast cancers, 13% lung cancers, and 13% gastro-intestinal tract cancers). Twenty-two cancers occurred 10 years (±5 years) after SSc diagnosis (14% breast cancers, 23% gastrointestinal (GI) tract cancers, and 18% lung cancers). Patients without any of the two autoantibodies (anti-centromere (ACA) and anti-topoisomerase (ATA-scl70) antibodies) were more prevalent in the early-onset cancer subgroup (14 vs. 6, p = 0.02). This study brought to light two peaks of cancer occurrence in SSc patients. Early-onset cancers were associated with SSc with a specific immunological signature. Late-onset cancers might be the consequence of a subtle interplay between repeated target organ inflammation, immunosuppressant use, mesenchymal cell dysfunction and subsequent genetic alterations.
Multifunctional Properties of Quercitrin-Coated Porous Ti-6Al-4V Implants for Orthopaedic Applications Assessed In Vitro
Authors: Llopis-Grimalt Maria Antonia , Arbós Aina , Gil-Mir Maria , Mosur Aleksandra , Kulkarni Prathamesh , Salito Armando , Ramis Joana M. , Monjo Marta
Published: March 2020

(1) One strategy to improve the outcome of orthopedic implants is to use porous implants with the addition of a coating with an antibacterial biomolecule. In this study, we aimed to produce and test the biocompatibility, the osteopromotive (both under normal conditions and under a bacterial challenge with lipopolysaccharide (LPS)) and antibacterial activities of a porous Ti-6Al-4V implant coated with the flavonoid quercitrin in vitro. (2) Porous Ti-6Al-4V implants were produced by 3D printing and further functionalized with quercitrin by wet chemistry. Implants were characterized in terms of porosity and mechanical testing, and the coating with quercitrin by fluorescence staining. Implant biocompatibility and bioactivity was tested using MC3T3-E1 preosteoblasts by analyzing cytotoxicity, cell adhesion, osteocalcin production, and alkaline phosphatase (ALP) activity under control and under bacterial challenging conditions using lipopolysaccharide (LPS). Finally, the antibacterial properties of the implants were studied using Staphylococcus epidermidis by measuring bacterial viability and adhesion. (3) Porous implants showed pore size of about 500 µm and a porosity of 52%. The coating was homogeneous over all the 3D surface and did not alter the mechanical properties of the Young modulus. Quercitrin-coated implants showed higher biocompatibility, cell adhesion, and osteocalcin production compared with control implants. Moreover, higher ALP activity was observed for the quercitrin group under both normal and bacterial challenging conditions. Finally, S. epidermidis live/dead ratio and adhesion after 4 h of incubation was lower on quercitrin implants compared with the control. (4) Quercitrin-functionalized porous Ti-6Al-4V implants present a great potential as an orthopedic porous implant that decreases bacterial adhesion and viability while promoting bone cell growth and differentiation.
Body Mass Index and Calprotectin Blood Level Correlation in Healthy Children: An Individual Patient Data Meta-Analysis
Authors: Grand Anais , Rochette Emmanuelle , Dutheil Frederic , Gozal David , Calcaterra Valeria , Berni Canani Roberto , Cobanoglu Nazan , Derikx Joep P. M. , Terrin Gianluca , Pereira Bruno , Merlin Etienne
Published: March 2020

Background: Calprotectin (CP) is a protein complex involved in many inflammatory diseases. Obesity is characterized by low-grade inflammation and elevated circulating levels of calprotectin. However, associations between body mass index (BMI) and calprotectin levels have not been explored in otherwise healthy children. Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed and Cochrane Library database up to July 2019. Healthy children’s blood calprotectin values were extracted, and potential correlations were explored. Results: A total of six studies that included data on 593 healthy children were identified. Median calprotectin value was 900.0 (482.0; 1700) ng·mL−1. Multivariable analysis showed no significant associations with age, sample type (serum vs. plasma), or sex. In contrast, a significant effect of BMI z-score (p < 0.001) emerged. Indeed, a positive correlation between BMI z-score and CP, was detected in girls (R: 0.48; p < 0.001) and boys (R: 0.39; p < 0.001). Conclusion: Calprotectin blood levels correlate with the degree of adiposity in healthy children, but are not affected by age, sex, or sample type (serum or plasma).