bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Nursing Care and Teaching: A Qualitative Approach
Authors: Martínez-Linares Jose Manuel , Martínez-Yébenes Rocío , Andújar-Afán Francisco Antonio , López-Entrambasaguas Olga María
Published: August 2019

Background: The reform of the Spanish higher education to adapt to the European Higher Education Area involves, among other issues, the students’ participation in the curriculum assessment. The aim is to understand the insights of both nursing professionals and current undergraduate students of nursing on the connection between the knowledge acquired throughout the degree and the professional healthcare practice. Methods: An exploratory, descriptive qualitative study was carried out at a Spanish University. By convenience sampling, twelve nursing professionals and twelve 4th-year students of the Degree in Nursing were included. In two phases, twelve semi-structured interviews and two focus groups were conducted in order to triangulate data. A thematic analysis of data was carried out, later to be coded by two researchers. Results: Two main themes were identified: Evidence-based nursing vs. experience-based nursing, and a theory-practice gap. The topics that were specifically highlighted were the coexistence between professionals who work according to evidence and those whose work is based on experience, and the lack of connection between the training received during the degree and actual healthcare practice. Conclusion: Nursing care work varies in terms of the implementation of evidence-based care. Nursing training is perceived as being affected by a theory-practice gap. To achieve the linking between nursing theory and practice, a great effort on stakeholders would be needed.
Unhealthy Lifestyle Associated with Higher Intake of Sugar-Sweetened Beverages among Malaysian School-Aged Adolescents
Authors: Gan Wan Ying , Mohamed Siti Fathiah , Law Leh Shii
Published: August 2019

High consumption of sugar-sweetened beverages (SSBs) among adolescents has turned into a global concern due to its negative impact on health. This cross-sectional study determined the amount of SSB consumption among adolescents and its associated factors. A total of 421 adolescents aged 13.3 ± 1.3 years (41.8% males, 58.2% females) completed a self-administered questionnaire on sociodemographic characteristics, physical activity, screen-viewing behavior, sleep quality, frequency of eating at fast food restaurants, home food availability, peer social pressure, parenting practice, and SSB consumption. Weight and height were measured. Results showed that the mean daily consumption of SSBs among adolescents was 1038.15 ± 725.55 mL. The most commonly consumed SSB was malted drink, while the least commonly consumed SSB was instant coffee. The multiple linear regression results revealed that younger age (β = −0.204, p < 0.001), higher physical activity (β = 0.125, p = 0.022), higher screen time (β = 0.147, p = 0.007), poorer sleep quality (β = 0.228, p < 0.001), and unhealthy home food availability (β = 0.118, p = 0.032) were associated with a higher SSB intake. Therefore, promoting a healthy lifestyle may help to reduce the excessive consumption of SSBs among adolescents.
DNA Hydroxymethylation at the Interface of the Environment and Nonalcoholic Fatty Liver Disease
Authors: Tommasi Stella , Besaratinia Ahmad
Published: August 2019

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of chronic liver disorders among adults, children, and adolescents, and a growing epidemic, worldwide. Notwithstanding the known susceptibility factors for NAFLD, i.e., obesity and metabolic syndrome, the exact cause(s) of this disease and the underlying mechanisms of its initiation and progression are not fully elucidated. NAFLD is a multi-faceted disease with metabolic, genetic, epigenetic, and environmental determinants. Accumulating evidence shows that exposure to environmental toxicants contributes to the development of NAFLD by promoting mitochondrial dysfunction and generating reactive oxygen species in the liver. Imbalances in the redox state of the cells are known to cause alterations in the patterns of 5-hydroxymethylcytosine (5hmC), the oxidative product of 5-methylcytosine (5mC), thereby influencing gene regulation. The 5hmC-mediated deregulation of genes involved in hepatic metabolism is an emerging area of research in NAFLD. This review summarizes our current knowledge on the interactive role of xenobiotic exposure and DNA hydroxymethylation in the pathogenesis of fatty liver disease. Increasing the mechanistic knowledge of NAFLD initiation and progression is crucial for the development of new and effective strategies for prevention and treatment of this disease.
Special Issue on Molecular Research Efforts in Urothelial Carcinoma: Summary of Included Topics
Authors: Hutterer Georg C.
Published: August 2019

This Special Issue of International Journal of Molecular Sciences (IJMS) covers one of the most intriguing and emerging fields in terms of molecular oncology and uro-oncologic research efforts over the recent years, namely urothelial carcinoma of the bladder (UCB), as well as urothelial carcinoma of the upper urinary tract (UTUC). A total of 8 articles published in this Special Issue highlight the current progress in molecular oncology and cancer genetics in UCB, including a wide range of research topics, such as FGFR-inhibitors, sarcopenia in UCB, molecular predictors of response following neoadjuvant chemotherapy, exercise cardiac training impacts in the murine UCB model, Obatoclax, tropomyosins as potential biomarkers, immunotherapeutic approaches, as well as a transcriptional analysis of immunohistochemically defined UCB-subgroups. Find a brief summary of the respective articles below.
Molecular Interactions Between Reactive Oxygen Species and Autophagy in Kidney Disease
Authors: Kaushal Gur P. , Chandrashekar Kiran , Juncos Luis A.
Published: August 2019

Reactive oxygen species (ROS) are highly reactive signaling molecules that maintain redox homeostasis in mammalian cells. Dysregulation of redox homeostasis under pathological conditions results in excessive generation of ROS, culminating in oxidative stress and the associated oxidative damage of cellular components. ROS and oxidative stress play a vital role in the pathogenesis of acute kidney injury and chronic kidney disease, and it is well documented that increased oxidative stress in patients enhances the progression of renal diseases. Oxidative stress activates autophagy, which facilitates cellular adaptation and diminishes oxidative damage by degrading and recycling intracellular oxidized and damaged macromolecules and dysfunctional organelles. In this review, we report the current understanding of the molecular regulation of autophagy in response to oxidative stress in general and in the pathogenesis of kidney diseases. We summarize how the molecular interactions between ROS and autophagy involve ROS-mediated activation of autophagy and autophagy-mediated reduction of oxidative stress. In particular, we describe how ROS impact various signaling pathways of autophagy, including mTORC1-ULK1, AMPK-mTORC1-ULK1, and Keap1-Nrf2-p62, as well as selective autophagy including mitophagy and pexophagy. Precise elucidation of the molecular mechanisms of interactions between ROS and autophagy in the pathogenesis of renal diseases may identify novel targets for development of drugs for preventing renal injury.
Inhibition of Ihh Reverses Temporomandibular Joint Osteoarthritis via a PTH1R Signaling Dependent Mechanism
Authors: Yang Hongxu , Zhang Mian , Liu Qian , Zhang Hongyun , Zhang Jing , Lu Lei , Xie Mianjiao , Chen Di , Wang Meiqing
Published: August 2019

The temporomandibular joint (TMJ), which is biomechanically related to dental occlusion, is often insulted by osteoarthritis (OA). This study was conducted to clarify the relationship between Indian hedgehog (Ihh) and parathyroid hormone receptor 1 (PTH1R) signaling in modulating the enhanced chondrocyte terminal differentiation in dental stimulated TMJ osteoarthritic cartilage. A gain- and loss-of-function strategy was used in an in vitro model in which fluid flow shear stress (FFSS) was applied, and in an in vivo model in which the unilateral anterior cross-bite (UAC) stimulation was adopted. Ihh and PTH1R signaling was modulated through treating the isolated chondrocytes with inhibitor/activator and via deleting Smoothened (Smo) and/or Pth1r genes in mice with the promoter gene of type 2 collagen (Col2-CreER) in the tamoxifen-inducible pattern. We found that both FFSS and UAC stimulation promoted the deep zone chondrocytes to undergo terminal differentiation, while cells in the superficial zone were robust. We demonstrated that the terminal differentiation process in deep zone chondrocytes promoted by FFSS and UAC was mediated by the enhanced Ihh signaling and declined PTH1R expression. The FFSS-promoted terminal differentiation was suppressed by administration of the Ihh inhibitor or PTH1R activator. The UAC-promoted chondrocytes terminal differentiation and OA-like lesions were rescued in Smo knockout, but were enhanced in Pth1r knockout mice. Importantly, the relieving effect of Smo knockout mice was attenuated when Pth1r knockout was also applied. Our data suggest a chondrocyte protective effect of suppressing Ihh signaling in TMJ OA cartilage which is dependent on PTH1R signaling.
Therapeutic Effect of Ecdysterone Combine Paeonol Oral Cavity Direct Administered on Radiation-Induced Oral Mucositis in Rats
Authors: Yang Li , Pan Jian
Published: August 2019

Radiation-induced oral mucositis represents an influential factor in cancer patients’ accepted radiation therapy, especially in head and neck cancer. This research investigates the treatment effect of Ecdysterone (a steroid derived from the dry root of Achyranthes bidentate) and Paeonol (a compound derived from Cortex Moutan) on radiation-induced oral mucositis and possible underlying mechanisms. Concisely, 20 Gy of X-rays (single-dose) irradiated the cranial localization in rats for the modeling of oral mucositis. The therapeutic effects of Ecdysterone-Paeonol oral cavity directly administered on radiation-induced oral mucositis were investigated by weight changes, direct observations, visual scoring methods, ulcer area/total area, and basic recovery days. Assessments of tumor necrosis factor α and interleukin-6 were performed to evaluate the inflammatory cytokines secretion in the damaged areas of tongues harvested post-treatment, and changes in signaling pathways were investigated by Western blotting. System Drug Target (SysDT) methods revealed the targets of Ecdysterone-Paeonol in order to support compound-target network construction. Four representative targets with different functions were chosen. The binding interactions between the compound and receptor were evaluated by molecular docking to investigate the binding affinity of the ligand to their protein targets. Ecdysterone-Paeonol, administered orally, effectively improved radiation-induced oral mucositis in rats, and the therapeutic effect was better than Ecdysterone administered orally on its own. In this study, calculational chemistry revealed that Ecdysterone-Paeonol affected 19 function targets associated with radiation-induced oral mucositis, including apoptosis, proliferation, inflammation, and wound healing. These findings position Ecdysterone-Paeonol as a potential treatment candidate for oral mucositis acting on multiple targets in the clinic.
ASD Phenotype—Genotype Associations in Concordant and Discordant Monozygotic and Dizygotic Twins Stratified by Severity of Autistic Traits
Authors: Hu Valerie W. , Devlin Christine A. , Debski Jessica J.
Published: August 2019

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder characterized by impaired social communication coupled with stereotyped behaviors and restricted interests. Despite the high concordance rate for diagnosis, there is little information on the magnitude of genetic contributions to specific ASD behaviors. Using behavioral/trait severity scores from the Autism Diagnostic Interview-Revised (ADI-R) diagnostic instrument, we compared the phenotypic profiles of mono- and dizygotic twins where both co-twins were diagnosed with ASD or only one twin had a diagnosis. The trait distribution profiles across the respective twin populations were first used for quantitative trait association analyses using publicly available genome-wide genotyping data. Trait-associated single nucleotide polymorphisms (SNPs) were then used for case-control association analyses, in which cases were defined as individuals in the lowest (Q1) and highest (Q4) quartiles of the severity distribution curves for each trait. While all of the ASD-diagnosed twins exhibited similar trait severity profiles, the non-autistic dizygotic twins exhibited significantly lower ADI-R item scores than the non-autistic monozygotic twins. Case-control association analyses of twins stratified by trait severity revealed statistically significant SNPs with odds ratios that clearly distinguished individuals in Q4 from those in Q1. While the level of shared genomic variation is a strong determinant of the severity of autistic traits in the discordant non-autistic twins, the similarity of trait profiles in the concordantly autistic dizygotic twins also suggests a role for environmental influences. Stratification of cases by trait severity resulted in the identification of statistically significant SNPs located near genes over-represented within autism gene datasets.
Early Sex Differences in the Immune-Inflammatory Responses to Neonatal Ischemic Stroke
Authors: Villapol Sonia , Faivre Valerie , Joshi Pooja , Moretti Raffaella , Besson Valerie C. , Charriaut-Marlangue Christiane
Published: August 2019

We recently reported that neonatal ischemia induces microglia/macrophage activation three days post-ischemia. We also found that female mice sustained smaller infarcts than males three months post-ischemia. The objective of our current study was to examine whether differential acute neuroinflammatory response and infiltrated immune cells occurs between male and females after three days post-ischemia. Permanent middle cerebral artery occlusion was induced in male and female postnatal 9-day-old (P9) mice, and mice were sacrificed three days after ischemia. Brains were analyzed for mRNA transcription after microglia magnetic cell sorting to evaluate M1 and M2 markers. FACS analysis was performed to assess myeloid infiltration and microglial expression of CX3 chemokine receptor 1 (CX3CR1). Inflammatory cytokine expression and microglia/macrophage activation were analyzed via in situ hybridization combined with immunofluorescence techniques. Lesion volume and cell death were measured. An increase in microglia/macrophages occurred in male versus female mice. The cells exhibited amoeboid morphology, and TNFα and ptgs2 (Cox-2) genes were more expressed in males. More myeloid cell infiltration was found in male versus female brains. However, we did not observe sex-dependent differences in the injured volume or cell death density. Our data show that sex differences in the acute microglial and immune responses to neonatal ischemia are likely both gene- and region-specific.
Lipid and Lipid Raft Alteration in Aging and Neurodegenerative Diseases: A Window for the Development of New Biomarkers
Authors: Mesa-Herrera Fátima , Taoro-González Lucas , Valdés-Baizabal Catalina , Diaz Mario , Marín Raquel
Published: August 2019

Lipids in the brain are major components playing structural functions as well as physiological roles in nerve cells, such as neural communication, neurogenesis, synaptic transmission, signal transduction, membrane compartmentalization, and regulation of gene expression. Determination of brain lipid composition may provide not only essential information about normal brain functioning, but also about changes with aging and diseases. Indeed, deregulations of specific lipid classes and lipid homeostasis have been demonstrated in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Furthermore, recent studies have shown that membrane microdomains, named lipid rafts, may change their composition in correlation with neuronal impairment. Lipid rafts are key factors for signaling processes for cellular responses. Lipid alteration in these signaling platforms may correlate with abnormal protein distribution and aggregation, toxic cell signaling, and other neuropathological events related with these diseases. This review highlights the manner lipid changes in lipid rafts may participate in the modulation of neuropathological events related to AD and PD. Understanding and characterizing these changes may contribute to the development of novel and specific diagnostic and prognostic biomarkers in routinely clinical practice.
Hepatic Cellular Distribution of Silica Nanoparticles by Surface Energy Modification
Authors: Lee A-Rang , Nam Kibeom , Lee Byeong Jun , Lee Seoung-Woo , Baek Su-Min , Bang Jun-Sun , Choi Seong-Kyoon , Park Sang-Joon , Kim Tae-Hwan , Jeong Kyu-Shik , Lee Dong Yun , Park Jin-Kyu
Published: August 2019

The cellular distribution of silica nanoparticles (NPs) in the liver is not well understood. Targeting specific cells is one of the most important issues in NP-based drug delivery to improve delivery efficacy. In this context, the present study analyzed the relative cellular distribution pattern of silica NPs in the liver, and the effect of surface energy modification on NPs. Hydrophobic NP surface modification enhanced NP delivery to the liver and liver sinusoid fFendothelial cells (LSECs). Conversely, hydrophilic NP surface modification was commensurate with targeting hepatic stellate cells (HSCs) rather than other cell types. There was no notable difference in NP delivery to Kupffer cells or hepatocytes, regardless of hydrophilic or hydrophobic NP surface modification, suggesting that both the targeting of hepatocytes and evasion of phagocytosis by Kupffer cells are not associated with surface energy modification of silica NPs. This study provides useful information to target specific cell types using silica NPs, as well as to understand the relationship between NP surface energy and the NP distribution pattern in the liver, thereby helping to establish strategies for cell targeting using various NPs.
Dual Role of Reactive Oxygen Species in Muscle Function: Can Antioxidant Dietary Supplements Counteract Age-Related Sarcopenia?
Authors: Damiano Simona , Muscariello Espedita , La Rosa Giuliana , Di Maro Martina , Mondola Paolo , Santillo Mariarosaria
Published: August 2019

Sarcopenia is characterized by the progressive loss of skeletal muscle mass and strength. In older people, malnutrition and physical inactivity are often associated with sarcopenia, and, therefore, dietary interventions and exercise must be considered to prevent, delay, or treat it. Among the pathophysiological mechanisms leading to sarcopenia, a key role is played by an increase in reactive oxygen and nitrogen species (ROS/RNS) levels and a decrease in enzymatic antioxidant protection leading to oxidative stress. Many studies have evaluated, in addition to the effects of exercise, the effects of antioxidant dietary supplements in limiting age-related muscle mass and performance, but the data which have been reported are conflicting. In skeletal muscle, ROS/RNS have a dual function: at low levels they increase muscle force and adaptation to exercise, while at high levels they lead to a decline of muscle performance. Controversial results obtained with antioxidant supplementation in older persons could in part reflect the lack of univocal effects of ROS on muscle mass and function. The purpose of this review is to examine the molecular mechanisms underlying the dual effects of ROS in skeletal muscle function and the analysis of literature data on dietary antioxidant supplementation associated with exercise in normal and sarcopenic subjects.
The Autophagy Status of Cancer Stem Cells in Gliobastoma Multiforme: From Cancer Promotion to Therapeutic Strategies
Authors: Ryskalin Larisa , Gaglione Anderson , Limanaqi Fiona , Biagioni Francesca , Familiari Pietro , Frati Alessandro , Esposito Vincenzo , Fornai Francesco
Published: August 2019

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor featuring rapid cell proliferation, treatment resistance, and tumor relapse. This is largely due to the coexistence of heterogeneous tumor cell populations with different grades of differentiation, and in particular, to a small subset of tumor cells displaying stem cell-like properties. This is the case of glioma stem cells (GSCs), which possess a powerful self-renewal capacity, low differentiation, along with radio- and chemo-resistance. Molecular pathways that contribute to GBM stemness of GSCs include mTOR, Notch, Hedgehog, and Wnt/β-catenin. Remarkably, among the common biochemical effects that arise from alterations in these pathways, autophagy suppression may be key in promoting GSCs self-renewal, proliferation, and pluripotency maintenance. In fact, besides being a well-known downstream event of mTOR hyper-activation, autophagy downregulation is also bound to the effects of aberrantly activated Notch, Hedgehog, and Wnt/β-catenin pathways in GBM. As a major orchestrator of protein degradation and turnover, autophagy modulates proliferation and differentiation of normal neuronal stem cells (NSCs) as well as NSCs niche maintenance, while its failure may contribute to GSCs expansion and maintenance. Thus, in the present review we discuss the role of autophagy in GSCs metabolism and phenotype in relationship with dysregulations of a variety of NSCs controlling pathways, which may provide novel insights into GBM neurobiology.
Periodontal Therapy for Improving Lipid Profiles in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Garde Siddharth , Akhter Rahena , Nguyen Mai Anh , Chow Clara K. , Eberhard Joerg
Published: August 2019

Periodontitis is a chronic inflammatory disorder often seen in patients with diabetes mellitus (DM). Individuals with diabetes are at a greater risk of developing cardiovascular complications and this may be related, in part, to lipid abnormalities observed in these individuals. The objective of this systematic review is to compile the current scientific evidence of the effects of periodontal treatment on lipid profiles in patients with type 2 diabetes mellitus. Through a systematic search using MEDLINE, EMBASE, PubMed, and Web of Science, 313 articles were identified. Of these, seven clinical trials which met all inclusion criteria were chosen for analysis. Between baseline and 3-month follow-up, there was a statistically significant reduction in the levels of total cholesterol (mean differences (MD) −0.47 mmol/L (95% confidence interval (CI), −0.75, −0.18, p = 0.001)), triglycerides (MD −0.20 mmol/L (95% CI −0.24, −0.16, p < 0.00001)) favouring the intervention arm, and a statistically significant reduction in levels of high density lipoprotein (HDL) (MD 0.06 mmol/L (95% CI 0.03, 0.08, p < 0.00001)) favouring the control arm. No significant differences were observed between baseline and 6-month follow-up levels for any lipid analysed. The heterogeneity between studies was high. This review foreshadows a potential benefit of periodontal therapy for lipid profiles in patients suffering from type 2 DM, however, well designed clinical trials using lipid profiles as primary outcome measures are warranted.
High-Fat Feeding in Time-Dependent Manner Affects Metabolic Routes Leading to Nervonic Acid Synthesis in NAFLD
Authors: Konstantynowicz-Nowicka Karolina , Berk Klaudia , Chabowski Adrian , Kasacka Irena , Bielawiec Patrycja , Łukaszuk Bartłomiej , Harasim-Symbor Ewa
Published: August 2019

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. The disturbances in the fatty acid composition of stored lipids are more important than the lipid species itself, which may influence the overall effect caused by these molecules. Thus, uncovering time-dependent changes in the fatty acid composition of accumulated lipid fractions after a high fat diet seems to be a new marker of NAFLD occurrence. The experiments were conducted on high fat fed Wistar rats. The blood and liver samples were collected at the end of each experimental week and used to assess the content of lipid fractions and their fatty acid composition by gas liquid chromatography. The expression of proteins from lipid metabolism pathways and of fatty acid exporting proteins were detected by Western blotting. In the same high fat feeding period, decreased de novo lipogenesis, increased β-oxidation and lipid efflux were demonstrated. The observed effects may be the first liver protective mechanisms against lipotoxicity. Nevertheless, such effects were still not sufficient to prevent the liver from proinflammatory lipid accumulation. Moreover, the changes in liver metabolic pathways caused the plasma nervonic acid concentration in sphingomyelin to decrease simultaneously with NAFLD development, which may be a steatosis occurrence prognostic marker.
A Modified Method to Assess Tidal Recruitment by Electrical Impedance Tomography
Authors: Muders Thomas , Hentze Benjamin , Simon Philipp , Girrbach Felix , Doebler Michael R.G. , Leonhardt Steffen , Wrigge Hermann , Putensen Christian
Published: August 2019

Avoiding tidal recruitment and collapse during mechanical ventilation should reduce the risk of lung injury. Electrical impedance tomography (EIT) enables detection of tidal recruitment by measuring regional ventilation delay inhomogeneity (RVDI) during a slow inflation breath with a tidal volume (VT) of 12 mL/kg body weight (BW). Clinical applicability might be limited by such high VTs resulting in high end-inspiratory pressures (PEI) during positive end-expiratory pressure (PEEP) titration. We hypothesized that RVDI can be obtained with acceptable accuracy from reduced slow inflation VTs. In seven ventilated pigs with experimental lung injury, tidal recruitment was quantified by computed tomography at PEEP levels changed stepwise between 0 and 25 cmH2O. RVDI was measured by EIT during slow inflation VTs of 12, 9, 7.5, and 6 mL/kg BW. Linear correlation of tidal recruitment and RVDI was excellent for VTs of 12 (R2 = 0.83, p < 0.001) and 9 mL/kg BW (R2 = 0.83, p < 0.001) but decreased for VTs of 7.5 (R2 = 0.76, p < 0.001) and 6 mL/kg BW (R2 = 0.71, p < 0.001). With any reduction in slow inflation VT, PEI decreased at all PEEP levels. Receiver-Operator-Characteristic curve analyses revealed that RVDI-thresholds to predict distinct amounts of tidal recruitment differ when obtained from different slow inflation VTs. In conclusion, tidal recruitment can sufficiently be monitored by EIT-based RVDI-calculation with a slow inflation of 9 mL/kg BW.
Review of Systemic Antibiotic Treatments in Children with Rhinosinusitis
Authors: Torretta Sara , Drago Lorenzo , Marchisio Paola , Gaini Lorenzo , Guastella Claudio , Moffa Antonio , Rinaldi Vittorio , Casale Manuel , Pignataro Lorenzo
Published: August 2019

Antibiotic treatment in paediatric rhinosinusitis is still a matter of debate, as the current guidelines have been drafted mainly based on clinical studies published before 2013. Recent modifications in the epidemiological basis of the disease might mean that current treatments are not completely adequate considering the evolving microbiological profile of the disease. The present paper reviews the role of systemic antibiotics in children with acute (ARS), chronic (CRS), recurrent (RARS), and complicated acute (CoARS) rhinosinusitis. A total of 14 studies (including 3 prospective non-randomised studies, 8 retrospective studies, and 3 prospective randomised studies) of the 115 initially identified papers were included in this review, corresponding to 13,425 patients. Five papers dealt with ARS, four papers with RARS or CRS, and five papers with CoARS; the remaining papers included patients with either ARS or CRS. Data about the effectiveness of antibiotic treatment in children with ARC, CRS, and CoARS is scarce, as only three randomised controlled trials have been published in the last decade, with contrasting results. There is an urgent need for dedicated controlled trials not only to test the actual clinical benefits deriving from the routine use of systemic antibiotics in different categories of patients but also to compare the effectiveness of various therapeutic protocols in terms of the type of antibacterial molecules and the duration of treatment.
Biomarkers of Acute Lung Injury The Individualized Approach: for Phenotyping, Risk Stratification and Treatment Surveillance
Authors: Murray Daniel D. , Itenov Theis Skovsgaard , Sivapalan Pradeesh , Eklöf Josefin Viktoria , Holm Freja Stæhr , Schuetz Philipp , Jensen Jens Ulrik
Published: August 2019

Do we need biomarkers of lung damage and infection: For what purpose and how should they be used properly? Biomarkers of lung damage can be used for diagnosis, risk stratification/prediction, treatment surveillance and adjustment of targeted therapy. Additionally, novel “omics” methods may offer a completely different and effective way of improving the understanding of pathogenesis of lung damage and a way to develop new candidate lung damage biomarkers. In the current review, we give an overview within the field of acute lung damage of (i) disease mechanism biomarkers, (ii) of “ready to use” evidence-based biomarker-guided lung infection management, (iii) of novel strategies of inflammatory phenotyping and how this can be used to tailor corticosteroid treatment, (iv) a future perspective of where “omics” technologies and mindsets may become increasingly important in developing new strategies for treatment and for understanding the development of acute lung damage.
Efficacy and Safety of Belatacept Treatment in Renal Allograft Recipients at High Cardiovascular Risk—A Single Center Experience
Authors: Neuwirt Hannes , Leitner-Lechner Irmgard , Kerschbaum Julia , Ertl Michael , Pöggsteiner Florian , Pölt Nicolas , Mätzler Julius , Sprenger-Mähr Hannelore , Rudnicki Michael , Schratzberger Peter , Eder Iris E. , Mayer Gert
Published: August 2019

Belatacept is an attractive option for immunosuppression after renal transplantation. Renal allograft function is superior when compared to calcineurin inhibitor (CNI) based therapy in “de novo” treated patients and it has also been proposed that individuals at high cardiovascular (CV) risk may benefit most. In this retrospective cohort study, we assessed the efficacy and safety of treating patients at high cardiovascular risk with Belatacept (n = 34, for 1194 observation months) when compared to a matched control group of 150 individuals under CNI immunosuppression (for 7309 months of observation). The estimated glomerular filtration rate (eGFR) increased for patients taking Belatacept but decreased during CNI-based therapy (+2.60 vs. −0.89 mL/min/1.73 m2/year, p = 0.006). In a multivariate Cox regression model, Belatacept remained the only significant factor associated with the improvement of eGFR (HR 4.35, 95%CI 2.39–7.93). Belatacept treatment was not a significant risk factor for renal allograft rejection or graft loss. In terms of safety, the only significant risk factor for de novo cardiovascular events was a pre-existing cerebrovascular disease, but Belatacept was not associated with a significant risk reduction. Belatacept treatment was not associated with an increased risk of severe infections, cytomegalo virus (CMV) or BK-virus reactivation, malignancy or death in the multivariate Cox regression analysis. Belatacept is an efficient and safe option for patients after renal transplantation at high cardiovascular risk.
Factors Influencing Early Marginal Bone Loss around Dental Implants Positioned Subcrestally: A Multicenter Prospective Clinical Study
Authors: Lombardi Teresa , Berton Federico , Salgarello Stefano , Barbalonga Erika , Rapani Antonio , Piovesana Francesca , Gregorio Caterina , Barbati Giulia , Di Lenarda Roberto , Stacchi Claudio
Published: August 2019

Early marginal bone loss (MBL) is a non-infective remodeling process of variable entity occurring within the first year after implant placement. It has a multifactorial etiology, being influenced by both surgical and prosthetic factors. Their impact remains a matter of debate, and controversial information is available, particularly regarding implants placed subcrestally. The present multicenter prospective clinical study aimed to correlate marginal bone loss around platform-switched implants with conical connection inserted subcrestally to general and local factors. Fifty-five patients were enrolled according to strict inclusion/exclusion criteria by four clinical centers. Single or multiple implants (AnyRidge, MegaGen, South Korea) were inserted in the posterior mandible with a one-stage protocol. Impressions were taken after two months of healing (T1), screwed metal-ceramic restorations were delivered three months after implant insertion (T2), and patients were recalled after six months (T3) and twelve months (T4) of prosthetic loading. Periapical radiographs were acquired at each time point. Bone levels were measured at each time point on both mesial and distal aspects of implants. Linear mixed models were fitted to the data to identify predictors associated with MBL. Fifty patients (25 male, 25 female; mean age 58.0 ± 12.8) with a total of 83 implants were included in the final analysis. The mean subcrestal position of the implant shoulder at baseline was 1.24 ± 0.57 mm, while at T4, it was 0.46 ± 0.59 mm under the bone level. Early marginal bone remodeling was significantly influenced by implant insertion depth and factors related to biological width establishment (vertical mucosal thickness, healing, and prosthetic abutment height). Deep implant insertion, thin peri-implant mucosa, and short abutments were associated with greater marginal bone loss up to six months after prosthetic loading. Peri-implant bone levels tended to stabilize after this time, and no further marginal bone resorption was recorded at twelve months after implant loading.
Effect of F-18 Fluorodeoxyglucose Uptake by Bone Marrow on the Prognosis of Head and Neck Squamous Cell Carcinoma
Authors: Lee Jeong Won , Ban Myung Jin , Park Jae Hong , Lee Sang Mi
Published: August 2019

The purpose of this study was to assess the relationship between F-18 fluorodeoxyglucose (FDG) uptake in bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) and survival in patients with head and neck squamous cell carcinoma (HNSCC). We retrospectively enrolled 157 HNSCC patients who underwent staging FDG PET/CT and subsequent treatment. On PET/CT, primary tumor metabolic characteristics, mean FDG uptake of BM (BM SUV), and BM-to-liver uptake ratio (BLR) were measured. The prognostic significance of FDG uptake of BM for predicting disease progression-free survival and distant failure-free survival was assessed using a Cox proportional hazards regression model. In univariate analysis for disease progression-free survival, increased BM SUV and BLR were associated with poor survival. In multivariate analysis, BLR (p = 0.044; hazard ratio, 1.96), TNM stage (p = 0.014; hazard ratio, 2.87) and maximum FDG uptake of the primary tumor (p = 0.046; hazard ratio, 2.38) were independently associated with disease progression-free survival. For distant failure-free survival, BLR, TNM stage, tumor size, and metabolic parameters of the primary tumor showed prognostic significance in univariate analysis. However, none of the variables showed significance in multivariate analysis. FDG uptake of BM in HNSCC patients might be a significant predictor for disease progression-free survival. Further studies with large patient population are needed to validate the results.
Paradigm Shifting of Systemic Chemotherapy for Unresectable Pancreatic Cancer in Japan
Authors: Furuse Junji
Published: August 2019

Systemic chemotherapy plays an important role in the treatment of pancreatic cancer, to improve the survival of patients with pancreatic cancer. Unresectable pancreatic cancer can be classified into three categories: metastatic, locally advanced, and hereditary pancreatic cancers. Furthermore, the second-line chemotherapy is required to prolong the survival. The combined regimens of oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GEM plus nab-PTX) have been recognized as the standard of care for advanced pancreatic cancer. However, the consensus of selection of the first-line chemotherapy still remains. Randomized controlled trials (RCTs) between FOLFIRINOX and GEM plus nab-PTX are ongoing for locally advanced and metastatic disease in Japan, respectively. Hereditary pancreatic cancer, especially associated with BRCA mutations, is responsive to platinum-containing regimens and/or poly (ADP-ribose) polymerase (PARP) inhibitors. It is becoming more important to examine the presence/absence of BRCA mutations to select the appropriate treatment strategy for individual patients. Although some S-1-based regimens have been investigated in the second-line treatment after GEM-based chemotherapy in Japan, no regime demonstrated survival benefit. Nanoliposomal irinotecan (nal-IRI) plus FF has been established as the standard of care in the second-line treatment in a global phase III trial (NAPOLI-1). A randomized phase II trial comparing FF plus nal-IRI with FF alone was also conducted in Japan to examine the efficacy and safety of the FF plus nal-IRI in Japanese patients.
Aortic Valve Sclerosis Adds to Prediction of Short-Term Mortality in Patients with Documented Coronary Atherosclerosis
Authors: Poggio Paolo , Cavallotti Laura , Myasoedova Veronika A. , Bonomi Alice , Songia Paola , Gripari Paola , Valerio Vincenza , Amato Mauro , Barbieri Simone , Faggiano Pompilio , Alamanni Francesco , Veglia Fabrizio , Pepi Mauro , Tremoli Elena , Baldassarre Damiano
Published: August 2019

Aims: Aortic valve sclerosis (AVSc), a non-uniform thickening of leaflets with an unrestricted opening, is characterized by inflammation, lipoprotein deposition, and matrix degradation. In the general population, AVSc predicts long-term cardiovascular mortality (+50%) even after adjustment for vascular risk factors and clinical atherosclerosis. We have hypothesized that AVSc is a risk-multiplier able to predict even short-term mortality. To address this issue, we retrospectively analyzed 90-day mortality of all patients who underwent isolated coronary artery bypass grafting (CABG) at Centro Cardiologico Monzino over a ten-year period (2006–2016). Methods: We analyzed 2246 patients and 90-day all-cause mortality was 1.5% (31 deaths). We selected only patients deceased from cardiac causes (n = 29) and compared to alive patients (n = 2215). A cardiologist classified the aortic valve as no-AVSc (n = 1352) or AVSc (n = 892). Cox linear regression and integrated discrimination improvement (IDI) analyses were used to evaluate AVSc in predicting 90-day mortality. Results: AVSc 90-day survival (97.6%) was lower than in no-AVSc (99.4%; p < 0.0001) with a hazard ratio (HR) of 4.0 (95%CI: 1.78, 9.05; p < 0.0001). The HR for AVSc, adjusted for propensity score, was 2.7 (95%CI: 1.17, 6.23; p = 0.02) and IDI statistics confirmed that AVSc significantly adds (p < 0.001) to the identification of high-risk patients than EuroSCORE II alone. Conclusion: Our data supports the hypothesis that a risk stratification strategy based on AVSc, added to ESII, may allow better recognition of patients at high-risk of short-term mortality after isolated surgical myocardial revascularization. Results from this study warrant further confirmation.
Focal Neuropathy Mimicking Focal Dystonia in a Child: Diagnostic and Rehabilitative Tools
Authors: Pavone Piero , Di Rosa Michelino , Musumeci Giuseppe , Caccamo Martina , Greco Filippo , Pavone Vito , Smilari Pierluigi , Santamato Andrea , Vecchio Michele
Published: August 2019

Object: Focal neuropathy results from an injury of any etiology that occurs in a peripheral nerve. The lesion may be followed by alteration of the sensory sphere (either dysesthesia or paresthesia with or without neuropathic pain), or by compensatory attitudes that are attributable to the altered contraction in muscles that are innervated by the injured nerve. Methods: We describe the case of a 13-year-old boy who attended our hospital for a focal neuropathy of the radial nerve. Conclusion: This neuropathy was revealed after the removal of a plaster Zimmer splint that was applied following a post-traumatic subluxation of the metacarpal-trapezoid joint.
An Assessment of Multiple Drivers Determining Woody Species Composition and Structure: A Case Study from the Kalahari, Botswana
Authors: Meyer Thoralf , Holloway Paul , Christiansen Thomas B. , Miller Jennifer A. , D’Odorico Paolo , Okin Gregory S.
Published: August 2019

Savannas are extremely important socio-economic landscapes, with pastoralist societies relying on these ecosystems to sustain their livelihoods and economy. Globally, there is an increase of woody vegetation in these ecosystems, degrading the potential of these multi-functional landscapes to sustain societies and wildlife. Several mechanisms have been invoked to explain the processes responsible for woody vegetation composition; however, these are often investigated separately at scales not best suited to land-managers, thereby impeding the evaluation of their relative importance. We ran six transects at 15 sites along the Kalahari transect, collecting data on species identity, diversity, and abundance. We used Poisson and Tobit regression models to investigate the relationship among woody vegetation, precipitation, grazing, borehole density, and fire. We identified 44 species across 78 transects, with the highest species richness and abundance occurring at Kuke (middle of the rainfall gradient). Precipitation was the most important environmental variable across all species and various morphological groups, while increased borehole density and livestock resulted in lower bipinnate species abundance, contradicting the consensus that these managed features increase the presence of such species. Rotating cattle between boreholes subsequently reduces the impact of trampling and grazing on the soil and maintains and/or reduces woody vegetation abundance.
Cross-Linking Strategies for Electrospun Gelatin Scaffolds
Authors: Campiglio Chiara Emma , Contessi Negrini Nicola , Farè Silvia , Draghi Lorenza
Published: August 2019

Electrospinning is an exceptional technology to fabricate sub-micrometric fiber scaffolds for regenerative medicine applications and to mimic the morphology and the chemistry of the natural extracellular matrix (ECM). Although most synthetic and natural polymers can be electrospun, gelatin frequently represents a material of choice due to the presence of cell-interactive motifs, its wide availability, low cost, easy processability, and biodegradability. However, cross-linking is required to stabilize the structure of the electrospun matrices and avoid gelatin dissolution at body temperature. Different physical and chemical cross-linking protocols have been described to improve electrospun gelatin stability and to preserve the morphological fibrous arrangement of the electrospun gelatin scaffolds. Here, we review the main current strategies. For each method, the cross-linking mechanism and its efficiency, the influence of electrospinning parameters, and the resulting fiber morphology are considered. The main drawbacks as well as the open challenges are also discussed.
Damping Enhancement Using Axially Functionally Graded Porous Structure Based on Acoustic Black Hole Effect
Authors: Zheng Weiguang , He Shiming , Tang Rongjiang , He Shuilong
Published: August 2019

The acoustic black hole (ABH) effect for damping flexural waves using axially functionally graded porous (FGP) structure is investigated. With proposed power-law porosity of FGP structure, ABH can be achieved and damping effect is enhanced. The physics are explained from divergent conditions of the integrated wave phase at composite ends. Numerical results show the damping effect is increased with power law index. The phenomenon is expounded by the characteristics of reflection coefficient and impedance. It indicates that increasing power law index leads to smaller wavelength along to the end, then the wave needs more oscillation cycles to travel, which leads to more energy absorption. Transient analysis for 2D FGP structure also shows the focalization and ABH effect of the flexural waves.
GFRP Bars Anchorage Resistance in a GFRP-Reinforced Concrete Bridge Barrier
Authors: Rostami Michael , Sennah Khaled , Hedjazi Saman
Published: August 2019

In the present paper, experimental and numerical investigations were conducted on concrete bridge barriers utilizing glass fiber reinforced polymer (GFRP) bars with a hook at their ends. Implementation of these hooked bars instead of the bent bars or headed-end bars in the bridge barriers presented in the Canadian Highway Bridge Design Code (CHBDC) was investigated on American Association for State Highway and Transportation Officials (AASHTO) test level 5 (TL-5) concrete bridge barriers. This research aimed to reach a cost effective and safe anchorage method for GFRP bars at the barrier–deck junction, compared to the conventional bend bars or headed-end bars. Therefore, an experimental program was developed and performed to qualify the use of the recently-developed, small radius hooked bars at the barrier–deck junction. The experimental findings were compared with the design factored applied transverse load specified in CHBDC for the design of the barrier–deck junction as well as factored applied bending moment obtained at the barrier–deck junction using a recently-conducted finite-element modeling. Satisfactory behavior for the developed hooked GFRP bars as well as their anchorage resistance was established and a reasonable factor of safety in design of barrier–deck joint was achieved.
A Generalized Process Targeting Model and an Application Involving a Production Process with Multiple Products
Authors: Abdel-Aal Mohammad A. M. , Selim Shokri Z.
Published: August 2019

This paper presents a generalized targeting model that subsumes most known targeting problems. In this paper, a recurrent state is defined as a condition that requires reprocessing or rework. The generalized model can accommodate one or two specifications limits and can be used for the following quality characteristics: The nominal-the-better, the larger-the-better, and the smaller-the-better. This model can be used to find the optimal mean of a quality characteristic, as well as the optimal specification limits. In addition, the paper studies the conditions under which the solution to the proposed model can provide a global solution. The paper shows that, for some of the special cases and under very general conditions, the optimal lower limit should be zero and the optimal upper limit should be infinity. This paper proves that the expected profits improve for the case where only a lower limit on the quality characteristic is used, if a recurrent state is included by adding an optimized upper limit. A special case of the model is used to study the problem of determining a common mean for multiple products, as well as the optimal upper specification limits for each product. A solution procedure for maximizing the expected profits and obtaining the optimal solution is introduced. A numerical example is presented.
A Remark on Structure of Projective Klingenberg Spaces over a Certain Local Algebra
Authors: Jukl Marek
Published: August 2019

This article is devoted to the projective Klingenberg spaces over a local ring, which is a linear algebra generated by one nilpotent element. In this case, subspaces of such Klingenberg spaces are described. The notion of the “degree of neighborhood” is introduced. Using this, we present the geometric description of subsets of points of a projective Klingenberg space whose arithmetical representatives need not belong to a free submodule.