bluuebunny/crossref_metadata_2025 huggingface dataset:
Medication Use among Pregnant Women from the 2015 Pelotas (Brazil) Birth Cohort Study
Authors: Lutz Bárbara Heather , Miranda Vanessa Iribarrem Avena , Silveira Marysabel Pinto Telis , Dal Pizzol Tatiane da Silva , Mengue Sotero Serrate , da Silveira Mariângela Freitas , Domingues Marlos Rodrigues , Bertoldi Andréa Dâmaso
Published: February 2020

Background: Medication use during pregnancy is a common practice that has been increasing in recent years. The aim of this study is to describe medication use among pregnant women from the 2015 Pelotas (Brazil) Birth Cohort Study. Methods: This paper relies on a population-based cohort study including 4270 women. Participants completed a questionnaire about the antenatal period, including information about medication use. We performed descriptive analyses of the sample and the medications used and adjusted analyses for the use of medications and self-medication. Results: The prevalence of medication use was 92.5% (95% CI 91.7–93.3), excluding iron salts, folic acid, vitamins, and other minerals. The prevalence of self-medication was 27.7% (95% CI 26.3–29.1). In the adjusted analysis, women who had three or more health problems during pregnancy demonstrated higher use of medicines. Self-medication was higher in lower income groups and among smokers and multiparous women (three pregnancies or more). Acetaminophen, scopolamine, and dimenhydrinate were the medications most commonly used. Conclusions: This study describes the pattern of drug use among pregnant women in a population-based cohort study, with a high prevalence of self-medication. Greater awareness of the risks of self-medication during pregnancy is required, focusing on groups more prone to this practice, as well as ensuring qualified multidisciplinary prenatal care.
Clinicians’ Perceptions of Norwegian Women’s Experiences of Infertility Diseases
Authors: Fernandes Alexandra , Skotnes Lotte-Lise , Major Maria , Falcão Pedro Fontes
Published: February 2020

Background: Norway has one of the best health systems in the world. However, it has a low birth rate, which decreased by 21.2% between 2009 and 2018, and one of the highest rates of infertility prevalence. The aim of this study is to understand how Norwegian doctors perceive female infertility diseases, namely those that are more difficult to diagnose and to treat, and that are more common in their practice. Method: Descriptive qualitative study was conducted with gynecologists and general practitioners. The sample resulted from the establishment of five criteria and on the doctors’ acceptance to participate in this study. Our sample comprised thirteen highly qualified and experienced doctors. Qualitative content analysis was the method chosen to analyze the collected data. Results: Clinical diseases (polycystic ovary syndrome, endometriosis and vulvodynia) and consequences of these diseases were the pinpointed themes. These led to a set of sub-themes: the main symptoms and the treatment of the diseases, from the perspective of both women and doctors (stigmatization, disturbances in women’s daily life, diagnostic delay, and governmental support). Conclusions: The three most relevant disorders mentioned were polycystic ovary syndrome, endometriosis and vulvodynia. These diseases cause several impacts on the lives of women, because they feel stigmatized and limited in their daily life and sexuality, and the diagnosis of these diseases takes too much time. Governments should better redistribute the financing of women’s health and allocate resources to specialized centers.
The Female Sexual Function Index: Transculturally Adaptation and Psychometric Validation in Spanish Women
Authors: Sánchez-Sánchez Beatriz , Navarro-Brazález Beatriz , Arranz-Martín Beatriz , Sánchez-Méndez Óscar , de la Rosa-Díaz Irene , Torres-Lacomba María
Published: February 2020

Background: The evaluation of sexual function is an important outcome in women who suffer some pelvic floor disorders (PFD). The Female Sexual Function Index (FSFI) is the most widely used questionnaire to evaluate the sexual health in female population. This study presents the adaptation and psychometric validation of the FSFI for Spanish women with PFD. Methods: The Spanish version of the FSFI was developed through the forward and backward translation process. The psychometric properties of reliability, validity, responsiveness, and feasibility were conducted in Spanish women with PFD who were assigned to the case or control group (with or without sexual dysfunction respectively). Results: A total of 323 Spanish women with PFD were recruited. The cross-cultural adaptation of the Spanish FSFI achieved a good semantic, conceptual, idiomatic, and content equivalence. The test-retest reliability was shown to be high in all of the cases. The convergent validity showed high results in the domain intercorrelations between each domain and total FSFI. The discriminant validity showed statistically significant differences between sexual dysfunction and control groups. The responsiveness was shown to be moderate to good in the dimensions and excellent in the total FSFI. Conclusions: Spanish FSFI can be used as a reliable, valid, responsive, and feasible instrument for assessing sexual function in women.
Exploring the Diagnostic Accuracy of the KidFit Screening Tool for Identifying Children with Health and Motor Performance-Related Fitness Impairments: A Feasibility Study
Authors: Milne Nikki , M Leong Gary , Hing Wayne
Published: February 2020

Child obesity is associated with poor health and reduced motor skills. This study aimed to assess the diagnostic accuracy of the KidFit Screening Tool for identifying children with overweight/obesity, reduced motor skills and reduced cardiorespiratory fitness. Fifty-seven children (mean age: 12.57 ± 1.82 years; male/female: 34/23) were analysed. The Speed and Agility Motor Screen (SAMS) and the Modified Shuttle Test-Paeds (MSTP) made up the KidFit Screening Tool. Motor Proficiency (BOT2) (Total and Gross) was also measured. BMI, peak-oxygen-uptake (VO2peak) were measured with a representative sub-sample (n = 25). Strong relationships existed between the independent variables included in the KidFit Screening Tool and; BMI (R2 = 0.779, p < 0.001); Gross Motor Proficiency (R2 = 0.612, p < 0.001) and VO2peak (mL/kg/min) (R2 = 0.754, p < 0.001). The KidFit Screening Tool has a correct classification rate of 0.84 for overweight/obesity, 0.77 for motor proficiency and 0.88 for cardiorespiratory fitness. The sensitivity and specificity of the KidFit Screening Tool for identifying children with overweight/obesity was 100% (SE = 0.00) and 78.95%, respectively (SE = 0.09), motor skills in the lowest quartile was 90% (SE = 0.095) and 74.47% (SE = 0.064), respectively, and poor cardiorespiratory fitness was 100% (SE = 0.00) and 82.35% (SE = 0.093), respectively. The KidFit Screening Tool has a strong relationship with health- and performance-related fitness, is accurate for identifying children with health- and performance-related fitness impairments and may assist in informing referral decisions for detailed clinical investigations.
Endoscopic Treatment and Pulmonary Rehabilitation for Management of Lung Abscess in Elderly Lymphoma Patients
Authors: Cascone Roberto , Sica Antonello , Sagnelli Caterina , Carlucci Annalisa , Calogero Armando , Santini Mario , Fiorelli Alfonso
Published: February 2020

Background: The management of lung abscess may be a challenge in elderly patients undergoing chemotherapy and/or radiotherapy for previous malignancy. Herein, we reported a case series of elderly patients with previous lymphoma undergoing endoscopic treatment followed by pulmonary rehabilitation for lung abscess. Methods: Our study population included a consecutive series of elderly patients with previous lymphoma and lung abscess. Suppurative infection was refractory with specific antibiotic therapy. In all cases, drainage was endoscopically inserted in lung abscess via video-bronchoscopy. This strategy allowed performing daily therapy with the installation of gentamicin directly into the abscess cavity. All patients underwent a respiratory rehabilitation program to speed up convalescence and allow early discharge. Results: After positioning the catheter through a bronchoscopic route and subsequent washing with gentamicin, all the patients in our study showed an improvement in clinical conditions with resolution of fever within a few days of starting the procedure with normalization of blood tests (mean hospital length 7 ± 0.73 days). A follow-up chest computed tomography scan showed a resolution of lung abscess within a mean of 27 ± 1.53 days. Conclusions: Endoscopic treatment with a rehabilitation program may be a valuable strategy for the management of lung abscess that is refractory to standard antibiotic therapy. Further and larger studiesshould be done to confirm our results.
School-based Physical Activity Interventions in Children and Adolescents: A Systematic Review
Authors: Vaquero-Solís Mikel , Gallego Damián Iglesias , Tapia-Serrano Miguel Ángel , Pulido Juan J. , Sánchez-Miguel Pedro Antonio
Published: February 2020

Background: The aim of this systematic review was to examinemotivational interventions based on physical activity as precursor of psychosocial benefits inside of the scholar context. Method: studies were identified in seven databases (Web of Science, Sport Discuss, Scopus, Eric, Pubmed, Psycinfo and Google Scholar). The search process was from June 2011 to September 2019. A total of 41 articles met the inclusion criteria. Results: 23 studies showed psychological effects after intervention and also 10 studies showed psychosocial effect after the intervention. The rest of the studies, although they presented changes, did not become significant.Conclusions: this systematic review showed the importance of motivational processes for the performance of physical activity and sport as a precursor of psychosocial changesand highlights the importance of strategies and the temporal nature of studies to maintain significant changes over time.Likewise, the study shows the future trend of motivational interventions, highlighting the female gender as participants of special interest, and changing the methodology through web-based interventions and active breaks or mental breaks during traditional subject classes.
Exposure of CuO Nanoparticles Contributes to Cellular Apoptosis, Redox Stress, and Alzheimer’s Aβ Amyloidosis
Authors: Shi Ying , Pilozzi Alexander R. , Huang Xudong
Published: February 2020

Fe2O3, CuO and ZnO nanoparticles (NP) have found various industrial and biomedical applications. However, there are growing concerns among the general public and regulators about their potential environmental and health impacts as their physio-chemical interaction with biological systems and toxic responses of the latter are complex and not well understood. Herein we first reported that human SH-SY5Y and H4 cells and rat PC12 cell lines displayed concentration-dependent neurotoxic responses to insults of CuO nanoparticles (CuONP), but not to Fe2O3 nanoparticles (Fe2O3NP) or ZnO nanoparticles (ZnONP). This study provides evidence that CuONP induces neuronal cell apoptosis, discerns a likely p53-dependent apoptosis pathway and builds out the relationship between nanoparticles and Alzheimer’s disease (AD) through the involvement of reactive oxygen species (ROS) and increased Aβ levels in SH-SY5Y and H4 cells. Our results implicate that exposure to CuONP may be an environmental risk factor for AD. For public health concerns, regulation for environmental or occupational exposure of CuONP are thus warranted given AD has already become a pandemic.
Prevalence of Colistin-Resistant, Carbapenem-Hydrolyzing Proteobacteria in Hospital Water Bodies and Out-Falls of West Bengal, India
Authors: Bardhan Taniya , Chakraborty Madhurima , Bhattacharjee Bornali
Published: February 2020

Indiscriminate use of antibiotics has resulted in a catastrophic increase in the levels of antibiotic resistance in India. Hospitals treat critical bacterial infections and thus can serve as reservoirs of multidrug resistant (MDR) bacteria. Hence, this study was conducted to gauge the prevalence patterns of MDR bacteria in hospital wastewater. Water samples collected from 11 hospitals and 4 environmental sources belonging to 5 most-densely populated districts of West Bengal, India were grown on MacConkey and Eosin Methylene Blue agar. A total of 84 (hospital-associated = 70, environmental water sources = 14) isolates were characterized. The predominant species found in water from hospital-associated areas (HAA) were Acinetobacter baumannii (22.9%), Escherichia coli (28.6 %), and Klebsiella pneumoniae (25.7%). Greater than 75% of the HAA isolates were found to be mcr-1 gene negative and colistinresistant. Meropenem non-susceptibility was also high among the HAA isolates at 58.6%, with the presence of the carbapenemase gene and blaNDM in 67.1% of the non-susceptible isolates. Among the three predominant species, significantly higher numbers of E. coli isolates were found to be non-susceptible to meropenem ((80%), p-value = 0.00432) and amikacin (AK (90%), p-value = 0.00037). This study provides evidence for the presence of high numbers of colistin-resistant and carbapenem-hydrolyzing Proteobacteriain hospital wastewater.
Geographical Patterns of Algal Communities Associated with Different Urban Lakes in China
Authors: Chen Shengnan , He Huiyan , Zong Rongrong , Liu Kaiwen , Miao Yutian , Yan Miaomiao , Xu Lei
Published: February 2020

Urban lakes play an important role in drainage and water storage, regulating urban microclimate conditions, supplying groundwater, and meeting citizens’ recreational needs. However, geographical patterns of algal communities associated with urban lakes from a large scale are still unclear. In the present work, the geographical variation of algal communities and water quality parameters in different urban lakes in China were determined. The water quality parameters were examined in the samples collected from north, central, south, and coastal economic zones in China. The results suggested that significant differences in water quality were observed among different geographical distribution of urban lakes. The highest total phosphorus (TP)(0.21 mg/L) and total nitrogen (TN) (3.84 mg/L) concentrations were found in XinHaiHu (XHH) lake, it also showed highest the nitrate nitrogen (NO3−-N) (0.39 mg/L),total organic carbon(TOC) (9.77 mg/L), and COD Mn (9.01 mg/L) concentrations among all samples. Environmental and geographic factors also cause large differences in algal cell concentration in different urban lakes, which ranged from 4700 × 104 to 247,800 × 104cell/L. Through light microscopy, 6 phyla were identified, which includes Chlorophyta, Bacillariophyta, Cyanophyta, Dinophyta, Euglenophyta, and Cryptophyta. Meanwhile, the heat map with the total 63 algal community composition at the genus level profile different urban lakes community structures are clearly distinguishable. Further analyses showed that the dominant genera were Limnothrix sp., Synedra sp., Cyclotella sp., Nephrocytium sp., Melosira sp., and Scenedesmus sp. among all samples. The integrated network analysis indicated that the highly connected taxa (hub) were Fragilaria sp., Scenedesmus sp., and Stephanodiscus sp. The water quality parameters of NO3−-N and NH4+-N had significant impacts on the structural composition of the algal community. Additionally, RDA further revealed distinct algal communities in the different urban lakes, and were influenced by NO2−-N, Fe, and algal cell concentrations. In summary, these results demonstrate that the pattern of algal communities are highly correlated with geographic location and water quality on a large scale, and these results also give us further understanding of the complex algal communities and effectively managing eutrophication of urban lakes.
Individualized Breakfast Programs or Glycogen Super-Compensation: Which Is the Better Performing Strategy? Insights from an Italian Soccer Referees Cohort
Authors: Regnoli Rebecca , Rovelli Marco , Gianturco Vincenzo , Pregliasco Fabrizio Ernesto , Bodini Bruno Dino , Gianturco Luigi
Published: February 2020

The role of soccer referees has grown in importance in the last decades, as has attention to their performance, which may be influenced and improved with specific and evolved training programs. Today, multiple specialists are working as a team in order to develop effective training programs. Moreover, for athletes, it is becoming more and more important to be attentive to nutrition. By considering such items, in this study, we aimed to investigate the nutritional habits of a group of referees belonging to the Italian Soccer Referees’ Association (on behalf of AIA-FIGC). Our main aim was to spread a “culture of nutrition” in refereeing, starting with a survey on referees’ breakfast attitudes and in order to disseminate such a “culture”, we chose top-level elite referees who were younger subjects (despite the average 4 years’ experience). Therefore, we enrolled 31 subjects (aged 22.74 ± 1.79, BMI 22.30 ± 1.53) and asked them about their breakfast habits. Then, for measuring their performance, we used the conventional fitness test named Yo-Yo (YYiR1), performed in three different sessions (test 1, test 2, test 3). Test 1 was carried out without any nutritional indications, test 2 was given after individualized breakfast suggestions by a designed dietician, and test 3 after an individualized glycogen super-compensation strategy. The Wilcoxon statistical analysis indicates that following an individualized breakfast strategy may enhance referees’ performance (p < 0.0001), whereas no significant effects were observed with the glycogen super-compensation option. However, further studies will be necessary to better address this topic and clarify whether high-carbohydrates (high-CHO) intake may be useful in other sports.
TGF–β3 Loaded Electrospun Polycaprolacton Fibre Scaffolds for Rotator Cuff Tear Repair: An in Vivo Study in Rats
Authors: Reifenrath Janin , Wellmann Mathias , Kempfert Merle , Angrisani Nina , Welke Bastian , Gniesmer Sarah , Kampmann Andreas , Menzel Henning , Willbold Elmar
Published: February 2020

Biological factors such as TGF–β3 are possible supporters of the healing process in chronic rotator cuff tears. In the present study, electrospun chitosan coated polycaprolacton (CS–g–PCL) fibre scaffolds were loaded with TGF–β3 and their effect on tendon healing was compared biomechanically and histologically to unloaded fibre scaffolds in a chronic tendon defect rat model. The biomechanical analysis revealed that tendon–bone constructs with unloaded scaffolds had significantly lower values for maximum force compared to native tendons. Tendon-bone constructs with TGF–β3-loaded fibre scaffolds showed only slightly lower values. In histological evaluation minor differences could be observed. Both groups showed advanced fibre scaffold degradation driven partly by foreign body giant cell accumulation and high cellular numbers in the reconstructed area. Normal levels of neutrophils indicate that present mast cells mediated rather phagocytosis than inflammation. Fibrosis as sign of foreign body encapsulation and scar formation was only minorly present. In conclusion, TGF–β3-loading of electrospun PCL fibre scaffolds resulted in more robust constructs without causing significant advantages on a cellular level. A deeper investigation with special focus on macrophages and foreign body giant cells interactions is one of the major foci in further investigations.
A Pilot Study on the Effects of l-Carnitine and Trimethylamine-N-Oxide on Platelet Mitochondrial DNA Methylation and CVD Biomarkers in Aged Women
Authors: Bordoni Laura , Sawicka Angelika K. , Szarmach Arkadiusz , Winklewski Pawel J. , Olek Robert A. , Gabbianelli Rosita
Published: February 2020

l-carnitine supplementation has been used for cardiovascular health protection for a long time. Recently, trimethylamine-N-oxide (TMAO), which is an end product of l-carnitine metabolism via the activity of microbiota, has been identified as a cardiovascular disease (CVD) biomarker. The aim of this study was to assess the effect of 6 months of l-carnitine supplementation in a group of aged women engaged in a regular physical training. Platelet mitochondrial DNA methylation, an emerging and innovative biomarker, lipid profile and TMAO levels have been measured. TMAO increased after l-carnitine supplementation (before 344.3 ± 129.8 ng/mL vs. after 2216.8 ± 1869.0 ng/mL; n = 9; paired t-test, p = 0.02). No significant effects on TMAO were exerted by training alone (n = 9) or by l-leucine supplementation (n = 12). TMAO levels after 6 months of l-carnitine supplementation were associated with higher low-density lipoprotein-cholesterol (LDL-c) (Spearman Rho = 0.518, p = 0.003) and total cholesterol (TC) (Spearman Rho = 0.407, p = 0.026) levels. l-carnitine supplementation increased D-loop methylation in platelets (+6.63%; paired t-test, p = 0.005). D-loop methylation was not directly correlated to the TMAO augmentation observed in the supplemented group, but its increase inversely correlated with TC (Pearson coefficient = −0.529, p = 0.029) and LDL-c (Pearson coefficient = −0.439, p = 0.048). This evidence supports the hypothesis that the correlation between l-carnitine, TMAO and atherosclerosis might be more complex than already postulated, and the alteration of mitochondrial DNA (mtDNA) methylation in platelets could be involved in the pathogenesis of this multifactorial disease.
The Intravitreal Injection of Lanosterol Nanoparticles Rescues Lens Structure Collapse at an Early Stage in Shumiya Cataract Rats
Authors: Nagai Noriaki , Fukuoka Yuya , Sato Kanta , Otake Hiroko , Taga Atsushi , Oka Mikako , Hiramatsu Noriko , Yamamoto Naoki
Published: February 2020

We designed an intravitreal injection formulation containing lanosterol nanoparticles (LAN-NPs) via the bead mill method and evaluated the therapeutic effect of LAN-NPs on lens structure collapse and opacification using two rat cataract models (SCR-N, rats with slight lens structure collapse; SCR-C, rats with the combination of a remarkable lens structure collapse and opacification). The particle size of lanosterol in the LAN-NPs was around 50–400 nm. A single injection of LAN-NPs (0.5%) supplied lanosterol into the lens for 48 h, and no irritation or muddiness was observed following repeated injections of LAN-NPs for 6 weeks (once every 2 days). Moreover, LAN-NPs repaired the slight collapse of the lens structure in SCR-N. Although the remarkable changes in the lens structure of SCR-C were not repaired by LAN-NP, the onset of opacification was delayed. In addition, the increase of cataract-related factors (Ca2+ contents, nitric oxide levels, lipid peroxidation and calpain activity levels) in the lenses of SCR-C was attenuated by the repeated injection of LAN-NPs. It is possible that a deficiency of lanosterol promotes the production of oxidative stress. In conclusion, it is difficult to improve serious structural collapse with posterior movement of the lens nucleus with a supplement of lanosterol via LAN-NPs. However, the intravitreal injection of LAN-NPs was found to repair the space and structural collapse in the early stages in the lenses.
A Simplified Method for Simultaneous Determination of α-Lipoic Acid and Low-Molecular-Mass Thiols in Human Plasma
Authors: Borowczyk Kamila , Olejarz Patrycja , Chwatko Grażyna , Szylberg Marcin , Głowacki Rafał
Published: February 2020

α-Lipoic acid, glutathione, cysteine, and cysteinylglycine can be applied as therapeutic agents in civilization diseases such as diabetes mellitus, cardiovascular diseases, and cancers. On the other hand, a higher concentration of homocysteine can result in health problems and has been indicated as an independent risk factor for cardiovascular disease and accelerated atherosclerosis. Here, the first simplified HPLC-UV assay that enables simultaneous determination of α-lipoic acid and low-molecular-mass thiols in plasma, reduces the number of steps, shortens the total time of sample preparation, and limits the amount of single-use polypropylene laboratory materials is described. The assay is based on reversed-phase high performance liquid chromatography with UV detection and simultaneous reduction of disulfide bound with tris(2-carboxyethyl)phosphine and the selective pre-column derivatization of the thiol group with 1-benzyl-2-chloropyridinium bromide. Linearity in the detector responses for plasma samples were observed in ranges: 0.12–5.0 nmol mL−1 for α-lipoic acid; 2.0–20.0 nmol mL−1 for glutathione, cysteinylglycine, and homocysteine; and 40.0–400.0 for cysteine. The LODs for α-lipoic acid and low-molecular-mass thiols were 0.08 and 0.12 nmol mL−1, respectively, while LOQs were 0.12 and 0.16 nmol mL−1, respectively. The usefulness of the proposed method has been proven by its application to real samples.
Dexamethasone Treatment Increases the Intracellular Calcium Level Through TRPV6 in A549 Cells
Authors: Jeon Bo-Hui , Yoo Yeong-Min , Jung Eui-Man , Jeung Eui-Bae
Published: February 2020

This study investigated the effect of dexamethasone (DEX) on intracellular calcium levels and the expressions of transient receptor potential cation channel subcomponent V member 6 (TRPV6), sodium-calcium exchanger 1 (NCX1), and plasma membrane calcium ATPase 1 (PMCA1) in A549 cells. The intracellular calcium level, by using the calcium indicator pGP-CMV-GCaMP6f, increased following DEX treatment for 6, 12, and 24 h in A549 cells. In addition, Rhod-4 assay after DEX treatment for 24 h showed that DEX increased the level of intracellular calcium. The expression of the calcium influx TRPV6 gene significantly increased, whereas the expressions of the calcium outflow NCX1 and PMCA1 genes significantly decreased with DEX treatment. The mRNA levels of surfactant protein genes SFTPA1, SFTPB, SFTPC, and SFTPD and the secreted airway mucin genes MUC1 and MUC5AC were investigated by treating cells with DEX. The DEX treatment decreased the mRNA levels of SFTPA1 and SFTPB but increased the mRNA levels of SFTPC and SFTPD. The MUC1 mRNA level was increased by DEX treatment, whereas MUC5AC mRNA was significantly decreased. These results indicate that DEX influences the intracellular calcium level through TRPV6, and affects pulmonary surfactant genes and secreted airway mucin genes in A549 cells.
Gene Prioritization through Consensus Strategy, Enrichment Methodologies Analysis, and Networking for Osteosarcoma Pathogenesis
Authors: Cabrera-Andrade Alejandro , López-Cortés Andrés , Jaramillo-Koupermann Gabriela , Paz-y-Miño César , Pérez-Castillo Yunierkis , Munteanu Cristian R. , González-Díaz Humbert , Pazos Alejandro , Tejera Eduardo
Published: February 2020

Osteosarcoma is the most common subtype of primary bone cancer, affecting mostly adolescents. In recent years, several studies have focused on elucidating the molecular mechanisms of this sarcoma; however, its molecular etiology has still not been determined with precision. Therefore, we applied a consensus strategy with the use of several bioinformatics tools to prioritize genes involved in its pathogenesis. Subsequently, we assessed the physical interactions of the previously selected genes and applied a communality analysis to this protein–protein interaction network. The consensus strategy prioritized a total list of 553 genes. Our enrichment analysis validates several studies that describe the signaling pathways PI3K/AKT and MAPK/ERK as pathogenic. The gene ontology described TP53 as a principal signal transducer that chiefly mediates processes associated with cell cycle and DNA damage response It is interesting to note that the communality analysis clusters several members involved in metastasis events, such as MMP2 and MMP9, and genes associated with DNA repair complexes, like ATM, ATR, CHEK1, and RAD51. In this study, we have identified well-known pathogenic genes for osteosarcoma and prioritized genes that need to be further explored.
Regulation of Osteoclast Differentiation at Multiple Stages by Protein Kinase D Family Kinases
Authors: Leightner Amanda C. , Mello Guimaraes Meyers Carina , Evans Michael D. , Mansky Kim C. , Gopalakrishnan Rajaram , Jensen Eric D.
Published: February 2020

Balanced osteoclast and osteoblast activity is necessary for skeletal health, whereas unbalanced osteoclast activity causes bone loss in many skeletal conditions. A better understanding of pathways that regulate osteoclast differentiation and activity is necessary for the development of new therapies to better manage bone resorption. The roles of Protein Kinase D (PKD) family of serine/threonine kinases in osteoclasts have not been well characterized. In this study we use immunofluorescence analysis to reveal that PKD2 and PKD3, the isoforms expressed in osteoclasts, are found in the nucleus and cytoplasm, the mitotic spindle and midbody, and in association with the actin belt. We show that PKD inhibitors CRT0066101 and CID755673 inhibit several distinct aspects of osteoclast formation. Treating bone marrow macrophages with lower doses of the PKD inhibitors had little effect on M-CSF + RANKL-dependent induction into committed osteoclast precursors, but inhibited their motility and subsequent differentiation into multinucleated mature osteoclasts, whereas higher doses of the PKD inhibitors induced apoptosis of the preosteoclasts. Treating post-fusion multinucleated osteoclasts with the inhibitors disrupted the osteoclast actin belts and impaired their resorptive activity. In conclusion, these data implicate PKD kinases as positive regulators of osteoclasts, which are essential for multiple distinct processes throughout their formation and function.
Targeting Insulin-Like Growth Factor 1 Receptor Delays M-Phase Progression and Synergizes with Aurora B Inhibition to Suppress Cell Proliferation
Authors: Yamagishi Akane , Ikeda Yuki , Ikeuchi Masayoshi , Yuki Ryuzaburo , Saito Youhei , Nakayama Yuji
Published: February 2020

The insulin-like growth factor 1 receptor (IGF1R) is a receptor-type tyrosine kinase that transduces signals related to cell proliferation, differentiation, and survival. IGF1R expression is often misregulated in tumor cells, but the relevance of this for cancer progression remains unclear. Here, we examined the impact of IGF1R inhibition on cell division. We found that siRNA-mediated knockdown of IGF1R from HeLa S3 cells leads to M-phase delays. Although IGF1R depletion causes partial exclusion of FoxM1 from the nucleus, quantitative real-time PCR revealed that the transcription of M-phase regulators is not affected by decreased levels of IGF1R. Moreover, a similar delay in M phase was observed following 2 h of incubation with the IGF1R inhibitors OSI-906 and NVP-ADW742. These results suggest that the M-phase delay observed in IGF1R-compromised cells is not caused by altered expression of mitotic regulators. Live-cell imaging revealed that both prolonged prometaphase and prolonged metaphase underlie the delay and this can be abrogated by the inhibition of Mps1 with AZ3146, suggesting activation of the Spindle Assembly Checkpoint when IGF1R is inhibited. Furthermore, incubation with the Aurora B inhibitor ZM447439 potentiated the IGF1R inhibitor-induced suppression of cell proliferation, opening up new possibilities for more effective cancer chemotherapy.
Is There a Role for Dual PI3K/mTOR Inhibitors for Patients Affected with Lymphoma?
Authors: Tarantelli Chiara , Lupia Antonio , Stathis Anastasios , Bertoni Francesco
Published: February 2020

The activation of the PI3K/AKT/mTOR pathway is a main driver of cell growth, proliferation, survival, and chemoresistance of cancer cells, and, for this reason, represents an attractive target for developing targeted anti-cancer drugs. There are plenty of preclinical data sustaining the anti-tumor activity of dual PI3K/mTOR inhibitors as single agents and in combination in lymphomas. Clinical responses, including complete remissions (especially in follicular lymphoma patients), are also observed in the very few clinical studies performed in patients that are affected by relapsed/refractory lymphomas or chronic lymphocytic leukemia. In this review, we summarize the literature on dual PI3K/mTOR inhibitors focusing on the lymphoma setting, presenting both the three compounds still in clinical development and those with a clinical program stopped or put on hold.
Defeating Antibiotic-Resistant Bacteria: Exploring Alternative Therapies for a Post-Antibiotic Era
Authors: Wang Chih-Hung , Hsieh Yi-Hsien , Powers Zachary M. , Kao Cheng-Yen
Published: February 2020

Antibiotics are one of the greatest medical advances of the 20th century, however, they are quickly becoming useless due to antibiotic resistance that has been augmented by poor antibiotic stewardship and a void in novel antibiotic discovery. Few novel classes of antibiotics have been discovered since 1960, and the pipeline of antibiotics under development is limited. We therefore are heading for a post-antibiotic era in which common infections become untreatable and once again deadly. There is thus an emergent need for both novel classes of antibiotics and novel approaches to treatment, including the repurposing of existing drugs or preclinical compounds and expanded implementation of combination therapies. In this review, we highlight to utilize alternative drug targets/therapies such as combinational therapy, anti-regulator, anti-signal transduction, anti-virulence, anti-toxin, engineered bacteriophages, and microbiome, to defeat antibiotic-resistant bacteria.
Poplar PdPTP1 Gene Negatively Regulates Salt Tolerance by Affecting Ion and ROS Homeostasis in Populus
Authors: Lu Yingying , Su Wanlong , Bao Yu , Wang Shu , He Fang , Wang Dongli , Yu Xiaoqian , Yin Weilun , Liu Chao , Xia Xinli
Published: February 2020

High concentrations of Na+ in saline soil impair plant growth and agricultural production. Protein tyrosine phosphorylation is crucial in many cellular regulatory mechanisms. However, regulatory mechanisms of plant protein tyrosine phosphatases (PTPs) in controlling responses to abiotic stress remain limited. We report here the identification of a Tyrosine (Tyr)-specific phosphatase, PdPTP1, from NE19 (Populus nigra × (P. deltoides × P. nigra). Transcript levels of PdPTP1 were upregulated significantly by NaCl treatment and oxidative stress. PdPTP1 was found both in the nucleus and cytoplasm. Under NaCl treatment, transgenic plants overexpressing PdPTP1 (OxPdPTP1) accumulated more Na+ and less K+. In addition, OxPdPTP1 poplars accumulated more H2O2 and O2·−, which is consistent with the downregulation of enzymatic ROS-scavengers activity. Furthermore, PdPTP1 interacted with PdMAPK3/6 in vivo and in vitro. In conclusion, our findings demonstrate that PdPTP1 functions as a negative regulator of salt tolerance via a mechanism of affecting Na+/K+ and ROS homeostasis.
The Impacts of Online Clothes Short Video Display on Consumers’ Perceived Quality
Authors: Ma Rong , Shao Bingjia , Chen Jiaqi , Dai Dan
Published: February 2020

In the context of the rapid development of online shopping, enterprises and consumers realized the importance of an effective online short video display. However, academics rarely explored the content of a short video display and its impacts on consumers’ perceptions. This paper discusses the impacts of this display form on consumers’ perceived quality via questionnaires and scenario experiments based on the existing literature and theories. A short video of clothes was the main research object. We used an experimental design that included 2 (time: long, short) × 2 (display perspectives: overall, specific) × 2 (scenarios: outdoors, indoors) groups of experiments, for a total of eight groups of scenario experiments, to verify our hypotheses. The results reveal that the short video display makes consumers have a higher perceived quality compared with the long video display. Compared with a video that only includes an overall view of the product, a video that provides both an overall view and the details of the product makes consumers have a higher perceived quality. Consumers were found to have a higher perceived quality of products shot outdoors compared with products shot indoors.
TmSpz6 Is Essential for Regulating the Immune Response to Escherichia coli and Staphylococcus aureus Infection in Tenebrio molitor
Authors: Edosa Tariku Tesfaye , Jo Yong Hun , Keshavarz Maryam , Bae Young Min , Kim Dong Hyun , Lee Yong Seok , Han Yeon Soo
Published: February 2020

Spätzle is an extracellular protein that activates the Toll receptor during embryogenesis and immune responses in Drosophila. However, the functions of the spätzle proteins in the innate immune response against bacteria or fungi in T. molitor are not well understood. Therefore, in this study, the open reading frame (ORF) of TmSpz6 was identified and its function in the response to bacterial and fungal infections in T. molitor was investigated using RNAi. The highest expression of TmSpz6 was in prepupae, and 3- and 6-day-old pupae, while remarkable expression was also observed in other stages. The tissue-specific expression analysis showed that TmSpz6 expression was highest in the hemocytes of larvae. TmSpz6 expression was highly induced when challenged with Escherichia coli, Staphylococcus aureus, or Candida albicans at 6 h post-injection; however, TmSpz6-silenced larvae were significantly more susceptible to only E. coli and S. aureus infection. The antimicrobial peptides (AMPs) gene expression analysis results show that TmSpz6 mainly positively regulated the expression of TmTencin-2 and -3 in response to E. coli and S. aureus infection. Collectively, these results suggest that TmSpz6 plays an important role in regulating AMP expression and increases the survival of T. molitor against E. coli and S. aureus.
Oogenesis of Hematophagous Midge Forcipomyia taiwana (Diptera: Ceratopogonidae) and Nuage Localization of Vasa in Germline Cells
Authors: Wang Szu-Chieh , Ching Yung-Hao , Krishnaraj Preethi , Chen Guan-Yu , Radhakrishnan Anna Shiny , Lee Hsien-Min , Tu Wu-Chun , Lin Ming-Der
Published: February 2020

Forcipomyia taiwana is an irritating hematophagous midge that preferentially attacks humans and affects leisure industries in Taiwan. Understanding the female reproductive biology of such pests would facilitate the development of pest control strategies. However, knowledge about oogenesis in the genus Forcipomyia is unavailable. Accordingly, we examined the ovariole structure and features of oogenesis in terms of the oocyte and the nurse cell. After being blood-fed, we observed a high degree of gonotrophic harmony—the synchronization of developing follicles. The follicle of the F. taiwana has only one nurse cell connected to the oocyte, which is distinct among hematophagous midges. In the nurse cell, we identified the perinuclear localization of the germline marker, Vasa. The Vasa localization is reminiscent of the nuclear envelope-associated nuage observed by electron microscopy. To determine whether F. taiwana Vasa (FtVasa) is an authentic nuage component, we produced transgenic flies expressing FtVasa in the female germline and proved that FtVasa was able to be localized to Drosophila nuage. By characterizing the oogenesis and Vasa expression in the germline cells of F. taiwana, this study extends knowledge about the female reproductive biology of hematophagous midges.
Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation
Authors: de Aguiar Greca Sophie-Christine , Kyrou Ioannis , Pink Ryan , Randeva Harpal , Grammatopoulos Dimitris , Silva Elisabete , Karteris Emmanouil
Published: February 2020

Background: Endocrine-disrupting chemicals (EDCs) are environmental chemicals/toxicants that humans are exposed to, interfering with the action of multiple hormones. Bisphenol A (BPA) is classified as an EDC with xenoestrogenic activity with potentially adverse effects in reproduction. Currently, a significant knowledge gap remains regarding the complete spectrum of BPA-induced effects on the human placenta. As such, the present study examined the effects of physiologically relevant doses of BPA in vitro. Methods: qRT-PCR, Western blotting, immunofluorescence, ELISA, microarray analyses, and bioinformatics have been employed to study the effects of BPA using nonsyncytialised (non-ST) and syncytialised (ST) BeWo cells. Results: Treatment with 3 nM BPA led to an increase in cell number and altered the phosphorylation status of p38, an effect mediated primarily via the membrane-bound estrogen receptor (GPR30). Nonbiased microarray analysis identified 1195 and 477 genes that were differentially regulated in non-ST BeWo cells, whereas in ST BeWo cells, 309 and 158 genes had altered expression when treated with 3 and 10 nM, respectively. Enriched pathway analyses in non-ST BeWo identified a leptin and insulin overlap (3 nM), methylation pathways (10 nM), and differentiation of white and brown adipocytes (common). In the ST model, most significantly enriched were the nuclear factor erythroid 2-related factor 2 (NRF2) pathway (3 nM) and mir-124 predicted interactions with cell cycle and differentiation (10 nM). Conclusion: Collectively, our data offer a new insight regarding BPA effects at the placental level, and provide a potential link with metabolic changes that can have an impact on the developing fetus.
From Spermiogram to Bio-Functional Sperm Parameters: When and Why Request Them?
Authors: Condorelli Rosita A. , Calogero Aldo E. , Russo Giorgio I. , La Vignera Sandro
Published: February 2020

The aim of this experimental study was to evaluate whether infertile patients may benefit from the evaluation of bio-functional sperm parameters in addition to the conventional semen analysis. To accomplish this, we evaluated the correlation between conventional and bio-functional sperm parameters based on their percentile distribution in search of a potential threshold of these latter that associates with conventional sperm parameter abnormalities. The study was conducted on 577 unselected patients with infertility lasting at least 12 months. We identified cut-off values according to the median of the population for mitochondrial membrane potential (MMP), number of alive spermatozoa, and chromatin abnormality. High MMP (HMMP) (≥46.25%) was associated with sperm concentration, sperm count, progressive motility, and normal form. Low MMP (LMMP) (≥36.5%) was found to be associated with semen volume, sperm concentration, total sperm count, progressive motility, total motility, and normal form. The number of alive spermatozoa (≥71.7%) was associated with sperm concentration and progressive motility whereas abnormal chromatin compactness (≥21.10%) was associated with sperm concentration, total sperm count, and progressive motility. The data would suggest that, for every increase in the percentile category of sperm concentration, the risk of finding an HMMP≤46.25 is reduced by 0.4 and by 0.66 for a total sperm count. This risk is also reduced by 0.60 for every increase in the percentile category of sperm progressive motility and by 0.71 for total sperm motility. Each increment of percentile category of the following sperm parameter was followed by a decrease in the risk of finding an LMMP≤36.5: sperm concentration 1.66, total sperm count 1.28, sperm progressive motility 1.27, total sperm motility 1.76, and normal form 1.73. Lastly, the data showed that, for every increase in the percentile category of total sperm count, the risk of finding an abnormal chromatin compactness ≤21.10 is reduced by 1.25 (1.04–1.51, p < 0.05) and an increase of total sperm motility is associated with a reduced risk by 1.44 (1.12–1.85, p < 0.05). Results suggest a correlation between bio-functional and conventional sperm parameters that impact the sperm fertilizing potential. Therefore, the evaluation of bio-functional sperm parameters by flow cytometry may be useful to explain some cases of idiopathic male infertility.
Circulating Arsenic is Associated with Long-Term Risk of Graft Failure in Kidney Transplant Recipients: A Prospective Cohort Study
Authors: Sotomayor Camilo G. , Groothof Dion , Vodegel Joppe J. , Gacitúa Tomás A. , Gomes-Neto António W. , Osté Maryse C. J. , Pol Robert A. , Ferreccio Catterina , Berger Stefan P. , Chong Guillermo , Slart Riemer H. J. A. , Rodrigo Ramón , Navis Gerjan J. , Touw Daan J. , Bakker Stephan J. L.
Published: February 2020

Arsenic is toxic to many organ systems, the kidney being the most sensitive target organ. We aimed to investigate whether, in kidney transplant recipients (KTRs), the nephrotoxic exposure to arsenic could represent an overlooked hazard for graft survival. We performed a prospective cohort study of 665 KTRs with a functional graft ≥1 year, recruited in a university setting (2008‒2011), in The Netherlands. Plasma arsenic was measured by ICP-MS, and dietary intake was comprehensively assessed using a validated 177-item food-frequency questionnaire. The endpoint graft failure was defined as restart of dialysis or re-transplantation. Median arsenic concentration was 1.26 (IQR, 1.04‒2.04) µg/L. In backwards linear regression analyses we found that fish consumption (std β = 0.26; p < 0.001) was the major independent determinant of plasma arsenic. During 5 years of follow-up, 72 KTRs developed graft failure. In Cox proportional-hazards regression analyses, we found that arsenic was associated with increased risk of graft failure (HR 1.80; 95% CI 1.28–2.53; p = 0.001). This association remained materially unaltered after adjustment for donor and recipient characteristics, immunosuppressive therapy, eGFR, primary renal disease, and proteinuria. In conclusion, in KTRs, plasma arsenic is independently associated with increased risk of late graft failure.
Thromboembolic Events Are Independently Associated with Liver Stiffness in Patients with Fontan Circulation
Authors: Alsaied Tarek , Possner Mathias , Lubert Adam M. , Trout Andrew T. , Gandhi Janvi P. , Garr BreAnn , Palumbo Joseph S. , Palermo Joseph J. , Lorts Angela , Veldtman Gruschen R. , Goldstein Stuart L. , Opotowsky Alexander , Dillman Jonathan R.
Published: February 2020

Background: Thromboembolism (TE) and Fontan-associated liver disease (FALD) are common and lead to significant morbidity in Fontan circulations. Risk factors for TE and the potential link between TE and FALD are not well understood. The objective of this study was to evaluate the association between TE and the severity of FALD based on radiologic liver stiffness. Methods: Using a retrospective cohort study design, 85 Fontan patients (aged 27.7 ± 8.2 years) who had liver stiffness measurement were included. Multivariable logistic regression was used to determine independent associations with TE. Results: Sixteen patients (19%) had a history of TE after the Fontan procedure at a mean age of 21.4 ± 15.0 years. Patients with TE were significantly older at the time of the last evaluation (33.8 ± 11.7 vs. 26.3 ± 6.5 years, p = 0.03). Liver stiffness by MRI and ultrasound was higher in the TE group (5.1 ± 1.4 vs. 4.3 ± 1.2 kPa, p = 0.04 and 2.8 ± 0.4 vs. 2.4 ± 0.5 m/s, p = 0.04, respectively). On multivariable analysis, higher liver stiffness (odds ratio (OR): 2.12, p = 0.03) and older age (OR: 1.11, p = 0.03) were associated with TE. Conclusions: This study found an association between TE, age, and radiologic liver stiffness.