bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Temperature-Sensitive Diseases and Attributable Fractions in China
Authors: Su Xuemei , Cheng Yibin , Wang Yu , Liu Yue , Li Na , Li Yonghong , Yao Xiaoyuan
Published: December 2019

Few studies have been carried out to systematically screen regional temperature-sensitive diseases. This study was aimed at systematically and comprehensively screening both high- and low-temperature-sensitive diseases by using mortality data from 17 study sites in China located in temperate and subtropical climate zones. The distributed lag nonlinear model (DLNM) was applied to quantify the association between extreme temperature and mortality to screen temperature-sensitive diseases from 18 kinds of diseases of eight disease systems. The attributable fractions (AFs) of sensitive diseases were calculated to assess the mortality burden attributable to high and low temperatures. A total of 1,380,713 records of all-cause deaths were involved. The results indicate that injuries, nervous, circulatory and respiratory diseases are sensitive to heat, with the attributable fraction accounting for 6.5%, 4.2%, 3.9% and 1.85%, respectively. Respiratory and circulatory diseases are sensitive to cold temperature, with the attributable fraction accounting for 13.3% and 11.8%, respectively. Most of the high- and low-temperature-sensitive diseases seem to have higher relative risk in study sites located in subtropical zones than in temperate zones. However, the attributable fractions for mortality of heat-related injuries were higher in temperate zones. The results of this research provide epidemiological evidence of the relative burden of mortality across two climate zones in China.
Breastfeeding and the Risk of Infant Illness in Asia: A Review
Authors: Lee Mi Kyung , Binns Colin
Published: December 2019

Infancy remains the most vulnerable period of human life for death, illness, and establishing a lifetime trajectory of growth and health. It is estimated that there are 5.3 million deaths under five years of age worldwide and approximately 800,000 lives could be saved by improving breastfeeding rates and duration. In Asia, an estimated 300,000–350,000 child deaths could be prevented with optimal breastfeeding and the majority would be under 12 months of age. We present a systematic review of studies of infection and breastfeeding in infants in Asia and further review interactions of selected infectious diseases and breastfeeding. Initially, 2459 records of possible interest were identified, 153 full text papers were reviewed in detail, and 13 papers describing diarrhoeal disease and/or acute respiratory tract infection were selected for inclusion in the review. Additional papers were selected to discuss specific diseases and their relationship to breastfeeding. The review found that a variety of methods were used with differing definitions of breastfeeding and diseases. Overall, breastfeeding when compared to the use of infant formula, is associated with significantly lower rates of diarrhoeal disease and lower respiratory tract infection, with a reduction of 50% or more to be expected, especially in infants under six months of age. The relationship between breastfeeding and specific diseases including measles and HTLV1 were reviewed. Breastfeeding reduces some disease rates, but there remain a few conditions where breastfeeding may be contra-indicated.
Antimicrobial Air Filters Using Natural Sea Salt Particles for Deactivating Airborne Bacterial Particles
Authors: Jeong Sang Bin , Heo Ki Joon , Lee Byung Uk
Published: December 2019

We developed an antimicrobial air filter using natural sea salt (NSS) particles. Airborne NSS particles were produced via an aerosol process and were continuously coated onto the surface of an air filter under various deposition times. The filtration efficiency and bactericidal performance of the NSS-coated filter against aerosolized bacterial particles (Staphylococcus epidermidis, Escherichia coli) were evaluated quantitatively. The filtration efficiency of the tested filter ranged from 95% to 99% depending on the deposition time, and the bactericidal performance demonstrated efficiencies of more than 98% against both tested bacterial bioaerosols when the NSS deposition ratio was more than 500 μg/cm2. The experimental results indicated that the NSS-coated filters have the potential to be used as effective antimicrobial air filters for decreasing environmental exposure to microbial contaminants.
Validity and Reliability of the WIMUTM Inertial Device for the Assessment of Joint Angulations
Authors: García-Rubio Javier , Pino José , Olivares Pedro R. , Ibáñez Sergio J.
Published: December 2019

Range of motion measurement is fundamental in the physical examination and functional evaluation of different joints. WIMUTM is an inertial device that allows the analysis of joint motion easily in real time. This study had a two-fold goal: (i) to evaluate the validity of WIMUTM on the measurement of different angle positions, compared with a standard goniometer and 2D video-based motion analysis software; and (ii) to evaluate the use of WIMUTM in the assessment of angulations in a joint, specifically assessing the validity and reliability of WIMUTM on the measurement of ankle dorsiflexion, compared to a standard goniometer and Kinovea. The intraclass correlation coefficient and Pearson´s correlation coefficient (r) were performed to calculate the concurrent validity, and Bland-Altman plots were performed to analyze agreement between measures. For the analysis of reliability, both relative and absolute indices were used. The results showed excellent validity and reliability of WIMUTM in the assessment of angle positions and ankle dorsiflexion. The current findings conclude that WIMUTM is a valid and reliable instrument to measure angle and joint motions. In short, WIMUTM provides a new clinical and sportive method of angle measurement.
How Good Is our Place—Implementation of the Place Standard Tool in North Macedonia
Authors: Gjorgjev Dragan , Dimovska Mirjana , Morris George , Howie John , Borota Popovska Mirjana , Topuzovska Latkovikj Marija
Published: December 2019

This study describes the implementation, in North Macedonia, of a “tool”, initially devised in Scotland, to generate community and stakeholder discussion about the places in which they live and notably a place’s capacity to generate health wellbeing and greater equity among citizens. In this study, the “place standard tool” (PST) is viewed from the perspective of creating places which can deliver a triple win of health and wellbeing, equity, and environmental sustainability. Skopje, North Macedonia’s capital, inevitably differs economically, culturally, and politically from Scotland, thus providing an opportunity to augment existing knowledge on adaptability of the tool in shaping agendas for policy and action. Тhe PST was tested through seminars with selected focus groups and an online questionnaire. Over 350 respondents were included. Information on priorities enabled the distillation of suggestions for improvement and was shared with the Mayor and municipal administration. Skopje citizens valued an approach which solicited their views in a meaningful way. Specific concerns were expressed relating to heavy traffic and related air and noise pollution, and care and maintenance of places and care services. Responses varied by geographic location. Application of the PST increased knowledge and confidence levels among citizens and enthusiasm for active involvement in decision making. Effective implementation relies heavily on: good governance and top-level support; excellent organization and good timing; careful training of interviewers and focus group moderators; and on prior knowledge of the participants/respondents.
Unexpected Prevalence of eae-Positive Escherichia coli in the Animas River, Durango, Colorado
Authors: Hamner Steve , Fenster Steven D. , Nance Benjamin T. , McLain Katherine A. , Parrish-Larson Kami S. , Morrow Michael W. , Ford Timothy E.
Published: December 2019

Since 2014, biology students at Fort Lewis College have studied the water quality of the Animas River in Durango, Colorado. Environmental microbiology and molecular biology techniques have been employed to study Escherichia coli isolates from the river and to define characteristics of the bacteria related to public health. E. coli was found in the river, as well as in culverts and tributary creeks that drain into the river within the Durango city limits. Concentrations of E. coli in the river occasionally exceeded the US EPA guideline of 126 CFU per 100 mL for recreational water use. Many of the E. coli isolates were able to be grown at 45 °C, an indication of mammalian origin. Unexpectedly, 8% of the isolates contained the intimin (eae) gene, a virulence gene characteristic of two pathotypes of E. coli, the enterohemorrhagic and enteropathogenic E. coli. Several isolates tested were resistant to multiple antibiotics commonly used in animal and human medicine. Further study is warranted to determine the source of these bacteria entering the Animas River, and to further characterize the possible disease potential of multi-antibiotic resistant and virulence gene-containing isolates found in a semi-rural/urban setting.
Sex Differences in Becoming a Current Electronic Cigarette User, Current Smoker and Current Dual User of Both Products: A Longitudinal Study among Mexican Adolescents
Authors: Rodríguez-Bolaños Rosibel , Arillo-Santillán Edna , Barrientos-Gutiérrez Inti , Zavala-Arciniega Luis , Ntansah Charity A. , Thrasher James F.
Published: December 2019

This study aimed to assess sex differences in predictors for becoming a current exclusive electronic cigarette (e-cigarette) user, current exclusive smoker, or current dual user (concurrent smoking and e-cigarette use). This longitudinal study included 2399 females and 2177 males who had tried neither cigarettes nor e-cigarettes at baseline and attended 57 middle schools in the three largest cities in Mexico. We estimated multinomial logistic models stratified by sex. At follow-up, the prevalence of current exclusive e-cigarette use was 6.4% for males and 5.5% for females; current exclusive smoking was similar among males (3.6%) and females (3.5%); dual use was 2.4% females and 1.8% males. In the adjusted model, current e-cigarette use among females was associated with baseline current drinking (ARR = 1.85; p < 0.05), having a job (ARR = 1.99; p < 0.05), higher technophilia (ARR = 1.27; p < 0.05), and higher positive smoking expectancies (ARR = 1.39; p < 0.05). Among males, only having friends who smoke cigarettes at baseline was a significant predictor of current exclusive e-cigarette use at follow-up (ARR = 1.44; p < 0.05). For both sexes, current exclusive smoking at follow-up was associated with baseline current drinking (male ARR = 2.56; p < 0.05; female ARR = 2.31; p < 0.05) and, among males, only with having a parent who smoked (ARR = 1.64; p < 0.05). For both sexes, dual use at follow-up was associated with baseline current drinking (male ARR = 3.52; p < 0.005; female ARR = 2.77; p < 0.05); among females, with having paid work (ARR = 2.50; p < 0.001); and among males, with parental smoking (ARR = 3.20; p < 0.05). Results suggested both common and different risk factors by sex, suggesting that interventions may need to consider targeting sex differences.
Perfectionism and a Healthy Attitude toward Oneself: Could Humor Be a Resource?
Authors: Di Fabio Annamaria , Smith Martin M. , Saklofske Donald H.
Published: December 2019

In the framework of the psychology of harmonization, the present study analyzes the relationships of humor styles with perfectionism, controlling for the effects of personality traits. One hundred and forty-eight Italian university students were administered the Italian versions of the HEXACO-60, the Humor Styles Questionnaire, and the short-form version of the Big Three Perfectionism Scale. Based on hierarchical regression analyses, humor styles accounted for a significant percentage of incremental variance beyond personality traits in relation to three major perfectionism factors. Humor styles may be a promising area for further research and intervention in relation to managing issues related to perfectionism in strengths-based preventative perspectives.
Long-Term Effectiveness of Liraglutide for Weight Management and Glycemic Control in Type 2 Diabetes
Authors: Mirabelli Maria , Chiefari Eusebio , Caroleo Patrizia , Arcidiacono Biagio , Corigliano Domenica Maria , Giuliano Stefania , Brunetti Francesco Saverio , Tanyolaç Sinan , Foti Daniela Patrizia , Puccio Luigi , Brunetti Antonio
Published: December 2019

Background: Liraglutide is the first glucagon-like peptide-1 receptor agonist (GLP-1 RA) based on the human GLP-1 sequence, with potential weight loss benefits, approved for the treatment of type 2 diabetes (T2D) mellitus. Herein, we aimed to assess the 5-year effectiveness of Liraglutide in the management of weight and glycometabolic control in a Southern Italian cohort of overweight/obese T2D patients, who were naïve to GLP-1 RAs. Patients and Methods: Forty overweight or obese patients treated with Liraglutide at doses up to 1.8 mg/day, in combination with one or more oral antidiabetic agents, were retrospectively assessed at baseline, during, and after 60 months of continuous therapy. Results: After 5 years of Liraglutide treatment, body weight decreased from 92.1 ± 20.5 kg to 87.3 ± 20.0 Kg (p < 0.001), with a mean reduction of 5.0 ± 7.0 Kg and a body mass index (BMI) decrement of −2.0 ± 3.1 Kg/m2. On Spearman’s univariate analysis, change in body weight was correlated with female gender and baseline BMI. Hemoglobin A1c (HbA1c) decreased from 7.9 ± 0.9% at baseline to 7.0 ± 0.7% at the end of the study period (p < 0.001), followed by a significant reduction in fasting plasma glucose. No significant differences emerged in other biochemical parameters, despite a trend toward improvement in lipid profile. Notwithstanding encouraging effects on several markers of cardiovascular disease (CVD), increments in the 5- and 10-year risk for the first atherosclerotic cardiovascular event were documented, as four incident cases of myocardial infarction. Conclusions: Prolonging treatment with Liraglutide can lead to durable benefits in relation to weight and glycemic control, with a greater impact on women. These results extend and corroborate previous observations, suggesting that gender per se may modulate the response to Liraglutide. Despite favorable effects on some established CVD risks factors, the long-term role of Liraglutide in primary prevention of CVD in patients with T2D remains controversial.
Leisure-Time Physical Activity Participation Trends 2014–2018: A Cross-Sectional Study in Poland
Authors: Biernat Elżbieta , Piątkowska Monika
Published: December 2019

Objective, the aim is an analysis of sociodemographic factors that had an essential relation with undertaking leisure-time physical activity—LTPA (with particular emphasis on World Health Organization (WHO) health recommendations) by adult Poles from a time-trend perspective. Methods, the paper is based on data retrieved from five large-scale surveys carried out on the representative samples of Poles aged 15–69 in 2014–2018 (n = 7347). In each wave, the Polish long version of the International Physical Activity Questionnaire was used. Results, the participation of Poles in LTPA constantly increases (p < 0.001) and the percentage of people meeting the dose of PA required for health recommendations is growing (on average, met by 43.9% of Polish men and 43.5% of women), which indicates a trend of behaviour of citizens of this country. The probability of realisation of WHO norms was determined by sex, age, place of residence and occupational status. Conclusion: it seems reasonable to develop Polish recommendations and guidelines for specific groups, including females and males, those who live in the villages and in the towns, different age groups: children/adolescents, adults (aged 50 to 59—most vulnerable to physical inactivity), the elderly, and various professional groups (especially farmers and physical workers).
Breast Cancer Gone Viral? Review of Possible Role of Bovine Leukemia Virus in Breast Cancer, and Related Opportunities for Cancer Prevention
Authors: Buehring Gertrude C. , Sans Hannah M.
Published: December 2019

This article is a literature review of research that explored the association of bovine leukemia virus (BLV) infection in humans with breast cancer. It summarizes and evaluates these publications. This review does not provide absolute proof that BLV is a cause of breast cancer, but, based on well-respected epidemiologic criteria for causation, it does suggest that BLV infection could be a breast cancer risk factor. Any expansion of the current understanding of breast cancer risk factors may increase possibilities to implement primary prevention strategies. The environmental role that BLV-infected cattle may play as a reservoir for infectious BLV offers possibilities for reducing or eliminating potential transmission of BLV from cattle to humans, and/or eliminating the reservoir.
Association of Drug Metabolic Enzyme Genetic Polymorphisms and Adverse Drug Reactions in Patients Receiving Rifapentine and Isoniazid Therapy for Latent Tuberculosis
Authors: Yu Ya-Yen , Tsao Shih-Ming , Yang Wen-Ta , Huang Wei-Chang , Lin Ching-Hsiung , Chen Wei-Wen , Yang Shun-Fa , Chiou Hui-Ling , Huang Yi-Wen
Published: December 2019

Weekly rifapentine and isoniazid therapy (3HP) is the most frequent treatment for latent tuberculosis infection (LTBI). However, the association between major adverse drug reactions (ADRs) and drug metabolic enzyme single-nucleotide polymorphisms (SNPs) remains unclear. In this study, 377 participants who received the 3HP regimen were recruited and examined for genotyping of CYP5A6, CYP2B6, CYP2C19, CYP2E1, and NAT2 SNPs. In our study, 184 participants (48.4%) developed ADRs. Moreover, CYP2C19 rs4986893 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 2.231 [1.015–4.906]), CYP2E1 rs2070676 (CC vs. CG+GG, OR [95% CI]: 1.563 [1.022–2.389]), and CYP2E1 rs2515641 (CC vs. CT+TT, OR [95% CI]: 1.903 [1.250–2.898]) were associated with ADR development. In conclusion, CYP2C19 and CYP2E1 SNPs may provide useful information regarding ADRs in LTBI patients receiving the 3HP regimen.
Induction of G2/M Phase Arrest by Diosgenin via Activation of Chk1 Kinase and Cdc25C Regulatory Pathways to Promote Apoptosis in Human Breast Cancer Cells
Authors: Liao Wen-Ling , Lin Jing-Yi , Shieh Jia-Ching , Yeh Hsiao-Fong , Hsieh Yi-Hsien , Cheng Yu-Chun , Lee Huei-Jane , Shen Chen-Yang , Cheng Chun-Wen
Published: December 2019

The anti-tumor activity of diosgenin, a new steroidal constituent present in fenugreek, on two human breast cancer cell lines, MCF-7 and Hs578T, was studied. Diosgenin treatment resulted in cell growth inhibition, cell cycle arrest, and apoptosis in concentration- and time-dependent manners in both cell lines. Western blot analyses of whole cell lysates for cell cycle proteins showed that diosgenin altered phosphorylated cyclin checkpoint1 (p-Chk1Ser345) and cyclin B expression, which resulted in G2/M phase blockade. Mechanistically, Cdc25C-Cdc2 signaling was involved in inactivating Chk1Ser345 by p53-dependence in MCF-7 cells and p21-dependence in Hs578T cells that are p53-deficient. Moreover, diosgenin induced a significant loss of the mitochondrial membrane potential in breast cancer cells, and prominently affected cell death through down-regulation of the anti-apoptotic protein, Bcl-2. This released cytochrome c and activated the caspase signaling cascade. Taken together, these findings reveal that the anti-proliferative activity of diosgenin involves the induction of G2/M phase arrest via modulating the Cdc25C-Cdc2-cyclin B pathway and mitochondria-mediated apoptosis in human breast cancer cell lines. This suggests the potential usefulness of diosgenin in treating breast cancer.
Feedback Regulation of Syk by Protein Kinase C in Human Platelets
Authors: Makhoul Stephanie , Dorschel Stephanie , Gambaryan Stepan , Walter Ulrich , Jurk Kerstin
Published: December 2019

The spleen tyrosine kinase (Syk) is essential for immunoreceptor tyrosine-based activation motif (ITAM)-dependent platelet activation, and it is stimulated by Src-family kinase (SFK)-/Syk-mediated phosphorylation of Y352 (interdomain-B) and Y525/526 (kinase domain). Additional sites for Syk phosphorylation and protein interactions are known but remain elusive. Since Syk S297 phosphorylation (interdomain-B) was detected in platelets, we hypothesized that this phosphorylation site regulates Syk activity via protein kinase C (PKC)-and cyclic adenosine monophosphate (cAMP)-dependent pathways. ADP, the GPVI-agonist convulxin, and the GPIbα-agonist echicetin beads (EB) were used to stimulate human platelets with/without effectors. Platelet aggregation and intracellular messengers were analyzed, along with phosphoproteins, by immunoblotting using phosphosite-specific antibodies or phos-tags. ADP, convulxin, and EB upregulated Syk S297 phosphorylation, which was inhibited by iloprost (cAMP pathway). Convulxin-stimulated Syk S297 phosphorylation was stoichiometric, transient, abolished by the PKC inhibitor GF109203X, and mimicked by the PKC activator PDBu. Convulxin/EB stimulated Syk S297, Y352, and Y525/526 phosphorylation, which was inhibited by SFK and Syk inhibitors. GFX and iloprost inhibited convulxin/EB-induced Syk S297 phosphorylation but enhanced Syk tyrosine (Y352/Y525/526) and substrate (linker adaptor for T cells (LAT), phospholipase γ2 (PLC γ2)) phosphorylation. GFX enhanced convulxin/EB-increases of inositol monophosphate/Ca2+. ITAM-activated Syk stimulates PKC-dependent Syk S297 phosphorylation, which is reduced by SFK/Syk/PKC inhibition and cAMP. Inhibition of Syk S297 phosphorylation coincides with enhanced Syk activation, suggesting that S297 phosphorylation represents a mechanism for feedback inhibition in human platelets.
Dietary Control of Ganglioside Expression in Mammalian Tissues
Authors: Okuda Tetsuya
Published: December 2019

Gangliosides are series of glycosphingolipids containing sialic acids in the oligosaccharide portion in mammalian cells. Gangliosides are a component of cellular membranes and play roles in modulating membrane function and the activity of membrane proteins. Abnormal expression and metabolism of gangliosides lead to the onset of several conditions in humans, such as neurologic diseases, diabetes, and cancer. A number of studies have been carried out to date to investigate the role of gangliosides in these diseases, and the effect of diet on tissue expression of gangliosides has recently become a topic of interest in this field. As gangliosides are degraded in the intestinal tract, ingested food-derived gangliosides are not directly absorbed into tissues in vivo, but the degradation products can be absorbed and affect ganglioside expression in the tissues. Recent studies have also shown that the expression of gangliosides in tissue cells can be indirectly induced by controlling the expression of ganglioside metabolism-related genes via the diet. These results indicate that dietary control can regulate the expression levels of gangliosides in tissues, which is expected to play a role in preventing and treating ganglioside-related diseases. This review introduces recent studies on the effect of diet on the expression of gangliosides in tissues, with a focus on our findings.
Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpen Aminodiols
Authors: Ozsvár Dániel , Nagy Viktória , Zupkó István , Szakonyi Zsolt
Published: December 2019

A library of steviol-based trifunctional chiral ligands was developed from commercially available natural stevisoide and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The key intermediate steviol methyl ester was prepared according to literature procedure. Depending on the epoxidation process, both cis- and trans-epoxyalcohols were obtained. Subsequent oxirane ring opening with primary and secondary amines afforded 3-amino-1,2-diols. The ring opening with sodium azide followed by a “click” reaction with alkynes resulted in dihydroxytriazoles. The regioselective ring closure of N-substituted aminodiols with formaldehyde was also investigated. The resulting steviol-type aminodiols were tested against a panel of human adherent cancer cell lines (A2780, SiHa, HeLa, and MDA-MB-231). It was consistently found that the N-benzyl substituent is an essential part within the molecule and the ring closure towards N-benzyl substituted oxazolidine ring system increased the antiproliferative activity to a level comparable with that of cisplatine. In addition, structure–activity relationships were examined by assessing substituent effects on the aminodiol systems.
Enhancing Neurogenesis of Neural Stem Cells Using Homogeneous Nanohole Pattern-Modified Conductive Platform
Authors: Cho Yeon-Woo , Kim Da-Seul , Suhito Intan Rosalina , Han Dong Keun , Lee Taek , Kim Tae-Hyung
Published: December 2019

Biocompatible platforms, wherein cells attach and grow, are important for controlling cytoskeletal dynamics and steering stem cell functions, including differentiation. Among various components, membrane integrins play a key role in focal adhesion of cells (18–20 nm in size) and are, thus, highly sensitive to the nanotopographical features of underlying substrates. Hence, it is necessary to develop a platform/technique that can provide high flexibility in controlling nanostructure sizes. We report a platform modified with homogeneous nanohole patterns, effective in guiding neurogenesis of mouse neural stem cells (mNSCs). Sizes of nanoholes were easily generated and varied using laser interference lithography (LIL), by changing the incident angles of light interference on substrates. Among three different nanohole patterns fabricated on conductive transparent electrodes, 500 nm-sized nanoholes showed the best performance for cell adhesion and spreading, based on F-actin and lamellipodia/filopodia expression. Enhanced biocompatibility and cell adhesion of these nanohole patterns ultimately resulted in the enhanced neurogenesis of mNSCs, based on the mRNAs expression level of the mNSCs marker and several neuronal markers. Therefore, platforms modified with homogeneous nanohole patterns fabricated by LIL are promising for the precise tuning of nanostructures in tissue culture platforms and useful for controlling various differentiation lineages of stem cells.
Examining Cardiomyocyte Dysfunction Using Acute Chemical Induction of an Ageing Phenotype
Authors: Masoud Said , McDonald Fraser , Bister Dirk , Kotecki Claire , Bootman Martin D. , Rietdorf Katja
Published: December 2019

Much effort is focussed on understanding the structural and functional changes in the heart that underlie age-dependent deterioration of cardiac performance. Longitudinal studies, using aged animals, have pinpointed changes occurring to the contractile myocytes within the heart. However, whilst longitudinal studies are important, other experimental approaches are being advanced that can recapitulate the phenotypic changes seen during ageing. This study investigated the induction of an ageing cardiomyocyte phenotypic change by incubation of cells with hydroxyurea for several days ex vivo. Hydroxyurea incubation has been demonstrated to phenocopy age- and senescence-induced changes in neurons, but its utility for ageing studies with cardiac cells has not been examined. Incubation of neonatal rat ventricular myocytes with hydroxyurea for up to 7 days replicated specific aspects of cardiac ageing including reduced systolic calcium responses, increased alternans and a lesser ability of the cells to follow electrical pacing. Additional functional and structural changes were observed within the myocytes that pointed to ageing-like remodelling, including lipofuscin granule accumulation, reduced mitochondrial membrane potential, increased production of reactive oxygen species, and altered ultrastructure, such as mitochondria with disrupted cristae and disorganised myofibres. These data highlight the utility of alternative approaches for exploring cellular ageing whilst avoiding the costs and co-morbid factors that can affect longitudinal studies.
Enhanced Osseointegration Capability of Poly(ether ether ketone) via Combined Phosphate and Calcium Surface-Functionalization
Authors: Sunarso  , Tsuchiya Akira , Toita Riki , Tsuru Kanji , Ishikawa Kunio
Published: December 2019

Biomedical applications of poly(ether ether ketone) (PEEK) are hindered by its inherent bioinertness and lack of osseointegration capability. In the present study, to enhance osteogenic activity and, hence, the osseointegration capability of PEEK, we proposed a strategy of combined phosphate and calcium surface-functionalization, in which ozone-gas treatment and wet chemistry were used for introduction of hydroxyl groups and modification of phosphate and/or calcium, respectively. Surface functionalization significantly elevated the surface hydrophilicity without changing the surface roughness or topography. The cell study demonstrated that immobilization of phosphate or calcium increased the osteogenesis of rat mesenchymal stem cells compared with bare PEEK, including cell proliferation, alkaline phosphatase activity, and bone-like nodule formation. Interestingly, further enhancement was observed for samples co-immobilized with phosphate and calcium. Furthermore, in the animal study, phosphate and calcium co-functionalized PEEK demonstrated significantly enhanced osseointegration, as revealed by a greater direct bone-to-implant contact ratio and bond strength between the bone and implant than unfunctionalized and phosphate-functionalized PEEK, which paves the way for the orthopedic and dental application of PEEK.
Cardiosomal microRNAs Are Essential in Post-Infarction Myofibroblast Phenoconversion
Authors: Morelli Marco B. , Shu Jun , Sardu Celestino , Matarese Alessandro , Santulli Gaetano
Published: December 2019

The inclusion of microRNAs (miRNAs) in extracellular microvesicles/exosomes (named cardiosomes when deriving from cardiomyocytes) allows their active transportation and ensures cell-cell communication. We hypothesize that cardiosomal miRNAs play a pivotal role in the activation of myofibroblasts following ischemic injury. Using a murine model of myocardial infarction (MI), we tested our hypothesis by measuring in isolated fibroblasts and cardiosomes the expression levels of a set of miRNAs, which are upregulated in cardiomyocytes post-MI and involved in myofibroblast phenoconversion. We found that miR-195 was significantly upregulated in cardiosomes and in fibroblasts isolated after MI compared with SHAM conditions. Moreover, primary isolated cardiac fibroblasts were activated both when incubated with cardiosomes isolated from ischemic cardiomyocytes and when cultured in conditioned medium of post-MI cardiomyocytes, whereas no significant effect was observed following incubation with cardiosomes or medium from sham cardiomyocytes. Taken together, our findings indicate for the first time that a cardiomyocyte-specific miRNA, transferred to fibroblasts in form of exosomal cargo, is crucial in the activation of myofibroblasts.
Cardiac-Specific Overexpression of Catalytically Inactive Corin Reduces Edema, Contractile Dysfunction, and Death in Mice with Dilated Cardiomyopathy
Authors: Tripathi Ranjana , Sullivan Ryan D. , Fan Tai-Hwang M. , Houng Aiilyan K. , Mehta Radhika M. , Reed Guy L. , Gladysheva Inna P.
Published: December 2019

Humans with dilated cardiomyopathy (DCM) and heart failure (HF) develop low levels of corin, a multi-domain, cardiac-selective serine protease involved in natriuretic peptide cleavage and sodium and water regulation. However, experimental restoration of corin levels markedly attenuates HF progression. To determine whether the beneficial effects of corin in HF require catalytic activity, we engineered cardiac overexpression of an enzymatically inactive corin transgene (corin-Tg(i)). On a wild-type (WT) background, corin-Tg(i) had no evident phenotypic effects. However, in a well-established genetic model of DCM, corin-Tg(i)/DCM mice had increased survival (p < 0.01 to 0.001) vs. littermate corin-WT/DCM controls. Pleural effusion (p < 0.01), lung edema (p < 0.05), systemic extracellular free water (p < 0.01), and heart weight were decreased (p < 0.01) in corin-Tg(i)/DCM vs. corin-WT/DCM mice. Cardiac ejection fraction and fractional shortening improved (p < 0.01), while ventricular dilation decreased (p < 0.0001) in corin-Tg(i)/DCM mice. Plasma atrial natriuretic peptide, cyclic guanosine monophosphate, and neprilysin were significantly decreased. Cardiac phosphorylated glycogen synthase kinase-3β (pSer9-GSK3β) levels were increased in corin(i)-Tg/DCM mice (p < 0.01). In summary, catalytically inactive corin-Tg(i) decreased fluid retention, improved contractile function, decreased HF biomarkers, and diminished cardiac GSK3β activity. Thus, the protective effects of cardiac corin on HF progression and survival in experimental DCM do not require the serine protease activity of the molecule.
The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells
Authors: Hughes-Parry Hannah E. , Cross Ryan S. , Jenkins Misty R.
Published: December 2019

The clinical success of chimeric antigen receptor (CAR) T cell immunotherapy in the treatment of haematological cancers has encouraged the extensive development of CAR design to improve their function and increase their applicability. Advancements in protein engineering have seen modifications to both the ecto- and endo-domains of the CAR, with recent designs targeting multiple antigens and including inducible elements. These developments are likely to play an important role in inducing effective CAR T cell responses in a solid tumour context, where clinical responses have not been effective to date. This review highlights the spectrum of novel strategies being employed in CAR design, including for example variations in targeting tumour antigens by utilising different ectodomain designs such as dual chain CARs, natural receptor or ligand-based CARs, and T cell receptor fusion constructs, and also reviews some of the innovative approaches to a “universal” CAR and various multi-antigen targeting CAR strategies. We also explore how choices in the endodomain impact CAR function and how these need to be considered in the overall CAR design.
Detection of Nonylphenol with a Gold-Nanoparticle-Based Small-Molecule Sensing System Using an ssDNA Aptamer
Authors: Kim A-Ru , Kim Sang-Heon , Kim Dabin , Cho Seo Won , Son Ahjeong , Yoon Moon-Young
Published: December 2019

Endocrine-disrupting chemicals (EDCs) threaten many kinds of life throughout the world. These compounds function the same as sexual hormones, inducing precocious puberty, gynecomastia, etc., in the human body. To prevent excess exposure to nonylphenol (NP), a simple and rapid detection system is needed. In this study, we develop a nonylphenol-specific aptamer from a random single-stranded DNA library and test a rapid sensor system based on the aptamer and gold nanoparticles (AuNPs). The aptamer was screened by a methodology involving reduced graphene oxide (rGO). As a result of screening and sequencing, a DNA aptamer was developed that recognizes the target with high binding affinity (Kd = 194.2 ± 65.9 nM) and specificity. The sensor system developed using the aptamer and gold nanoparticles is sensitive (LOD = 2.239 nM). Circular dichroism (CD) spectrometry results show that the free aptamer binds to the target molecule. The aptamer was characterized using gold nanoparticles to measure UV absorbance. Our results suggest that the sensor system developed using this aptamer is useful for field diagnosis of small molecules.
Folding Rate Optimization Promotes Frustrated Interactions in Entangled Protein Structures
Authors: Norbiato Federico , Seno Flavio , Trovato Antonio , Baiesi Marco
Published: December 2019

Many native structures of proteins accomodate complex topological motifs such as knots, lassos, and other geometrical entanglements. How proteins can fold quickly even in the presence of such topological obstacles is a debated question in structural biology. Recently, the hypothesis that energetic frustration might be a mechanism to avoid topological frustration has been put forward based on the empirical observation that loops involved in entanglements are stabilized by weak interactions between amino-acids at their extrema. To verify this idea, we use a toy lattice model for the folding of proteins into two almost identical structures, one entangled and one not. As expected, the folding time is longer when random sequences folds into the entangled structure. This holds also under an evolutionary pressure simulated by optimizing the folding time. It turns out that optmized protein sequences in the entangled structure are in fact characterized by frustrated interactions at the closures of entangled loops. This phenomenon is much less enhanced in the control case where the entanglement is not present. Our findings, which are in agreement with experimental observations, corroborate the idea that an evolutionary pressure shapes the folding funnel to avoid topological and kinetic traps.
Course Analysis of Library and Information Science in Korea
Authors: Mo Yelim , Seon Euntaek , Park Goun , Kim Haklae
Published: December 2019

Curriculums play a key role in implementing the educational goals and directions of a university. Universities regularly update their curriculums to actively respond to internal and external environmental changes. Korean universities face challenges, including a steady decline in enrollment and demand-oriented convergence education. Because of the nature of convergence science, library and information science should respond more actively to new challenges. This study analyzes the current status of library and information science courses according to subjects and universities. Data was collected from the websites of each university, and various methods such as text analysis, frequency analysis, and network analysis were applied to investigate current status of LIS in Korea.
Composition and Insecticidal Activity of Essential Oil of Bacopa caroliniana and Interactive Effects of Individual Compounds on the Activity
Authors: Liu Tai-Ti , Chao Louis Kuo-Ping , Hong Kai-Siang , Huang Yi-Jhen , Yang Tsung-Shi
Published: December 2019

Bacopa caroliniana (BC) is a perennial creeping herb and popular aquarium plant. This plant is easily cultivated; consequently, it has the potential to be a raw material which is readily available for mass production if it contains useful bioactive substances. The information about the functionality of this plant has been very limited. Therefore, the aims of this research were to analyze the composition of the essential oil (EO) of BC and to study its insecticidal effect on rice weevils. Moreover, the interactive effects of active compounds of the EO on this activity were also investigated. A total of 18 volatile compounds was identified, accounting for ca. 94% of the BC-EO in terms of quantity. Of them, α-terpinolene was the largest compound. The impact of individual volatile compounds on the inhibition of acetylcholine esterase and insecticidal activity were determined. α-Terpinolene exhibited the highest activity on these assays. Both additive and synergistic effects existed in terms of the insecticidal activity. Many compounds found in the BC-EO are widely present in other EOs. Thus, the information obtained from this study is useful for EO-related research, applications in selecting EOs or in seeking the best combination of EOs or individual compounds to achieve efficient insecticidal effects.
Trends in the Prevalence of Atrial Septal Defect and Its Associated Factors among Congenital Heart Disease Patients in Vietnam
Authors: Xuan Tuan Ho , The Phuoc Long Phan , Duy Kien Vu , Manh Cuong Le , Van Son Nguyen , Dalla-Pozza Robert
Published: December 2019

Atrial septal defect (ASD) is a non-physiologic communication between the two atria, allowing the shunt between systemic and pulmonary circulation. Data about ASD prevalence among congenital heart disease patients (CHD) in Vietnam are still scarce. We aim to assess the trends in the prevalence of ASD patients and associated factors among CHD patients. This was a cross-sectional study, with data collected from medical records from 1220 CHD patients in Da Nang hospital from 1 January 2010 to 31 December 2015. Descriptive statistics were used to estimate the prevalence of ASD among CHD patients. Comparative statistical methods were used to compare groups and logistic regression to access associated factors with ASD. The overall prevalence of ASD among CHD patients was 18.5% between 2010 and 2015. The prevalence varied between periods, ranging between 15% and 31.9% during the period. The prevalence of ASD women among CHD (25.9%) was significantly higher than for men (16.0%). The prevalence of ASD increased gradually when the age group increased. The factors associated with increased ASD prevalence were being a female and being in an older age group. The findings suggest that targeted policy should provide more-specific health-care services of ASD for women and older patients.
Immunomodulation of Murine Chronic DSS-Induced Colitis by Tuftsin–Phosphorylcholine
Authors: Ben-Ami Shor Dana , Lachnish Jordan , Bashi Tomer , Dahan Shani , Shemer Asaf , Segal Yahel , Shovman Ora , Halpert Gilad , Volkov Alexander , Barshack Iris , Amital Howard , Blank Miri , Shoenfeld Yehuda
Published: December 2019

Helminths or their products can immunomodulate the host immune system, and this phenomenon may be applied as the basis of new anti-inflammatory treatments. Previously, we have shown the efficacy of tuftsin–phosphorylcholine (TPC), based on a helminth product, in four animal models of autoimmune diseases: arthritis, colitis, systemic lupus erythematosus, and experimental autoimmune encephalomyelitis. We demonstrated that TPC reduced inflammatory process ex vivo in peripheral blood lymphocytes (PBLs) and in biopsies from giant-cell arteritis. In the present study, we assessed the therapeutic potential of TPC treatment on a chronic colitis murine model. C57BL/6 mice with chronic colitis were treated with TPC after the third cycle of 2% dextran sodium sulfate (DSS). Oral TPC treatment resulted in amelioration of the colitis clinical manifestations exemplified by reduced disease activity index (DAI) score, expansion of mesenteric lymph nodes (MLN) T regulatory cells (shown by Fluorescence Activated Cell Sorting (FACS)), significant reduction in the expression of pro-inflammatory cytokines (IL-1β, IL17, IL-6, TNFα), and elevation in the expression of anti-inflammatory cytokine IL-10 (shown by RT-PCR). This study demonstrated the potential immunomodulatory effects of oral administration of TPC in a chronic colitis murine model. Further clinical trials are needed in order to evaluate this novel approach for the treatment of patients with inflammatory bowel disease.
Preoperative Ascorbic Acid Levels in Proximal Femur Fracture Patients Have No Postoperative Clinical Impact, While Ascorbic Acid Levels upon Discharge Have a Major Effect on Postoperative Outcome
Authors: Hill-Mündel Katharina , Schlegl Johannes , Biesalski Hans Konrad , Ehnert Sabrina , Schröter Steffen , Bahrs Christian , Nohr Donatus , Nüssler Andreas K. , Ihle Christoph
Published: December 2019

Proximal femur fractures show a high prevalence in elderly patients and are associated with an elevated risk of multimorbidity and early mortality. Recovery is impaired by malnutrition and oxidative stress, which is affected by antioxidants such as ascorbic acid (AA). This study monitored AA levels during hospitalization of patients with a proximal femur to investigate the influence of AA status to the clinical outcome. AA levels of 25 elderly patients with a proximal femur fracture were measured during hospitalization using high performance liquid chromatography. Plasma samples were collected preoperatively, on the first day after surgery, on the third day after surgery and on the day of discharge. Nutritional Risk Screening 2002 (NRS) and Mini Nutritional Assessment (MNA) were assessed to evaluate the nutritional status. In patients with proximal femoral fractures, preoperative AA concentrations were significantly lower compared to elderly patients without an acute fracture. A significant decrease of 33.8% in AA plasma level was measured on the day after surgery with a significant recovery up to the time of discharge. The preoperative AA status did not have any significant effect on clinical outcome. However, inadequate AA levels (<50 µmol/L) upon discharge significantly increased the incidence and the severity of postoperative complications. These results indicate that the AA status upon discharge has a greater impact on clinical outcome than assumed, and therefore, AA supplementation during hospitalization should be considered.
Craniofacial Asymmetry from One to Three Years of Age: A Prospective Cohort Study with 3D Imaging
Authors: Launonen Anniina M. , Vuollo Ville , Aarnivala Henri , Heikkinen Tuomo , Pirttiniemi Pertti , Valkama A. Marita , Harila Virpi
Published: December 2019

Deformational plagiocephaly (DP) is considered a risk factor for facial asymmetry. This cohort-based, prospective, follow-up study used three-dimensional (3D) stereophotogrammetry to assess the development of facial asymmetry in a normal birth cohort and to investigate the impact of DP on facial asymmetry for the age range of one to three years. The study sample consisted of 75 children: 35 girls (47%) and 40 (53%) boys recruited from Oulu University Hospital. A total of 23 (31%) subjects had a history of DP in infancy. 3D facial images were obtained at the mean (SD) age of 1.01 (0.04) year old at T1 and 3.02 (0.14) years old at T2. To determine facial asymmetry, both landmark-based and surface-based facial symmetry methods were used. As measured with the surface-based methods, upper facial symmetry improved from T1 to T2 (p < 0.05). As measured with the landmark-based methods, facial symmetry improved on the upper and lower jaw from T1 to T2 (p < 0.05). The asymmetric effect of DP on the upper parts of the face tends to correct spontaneously during growth. Results indicate that previous DP does not seem to transfer to facial or occlusal asymmetry at the age of three years old.
Selective ß2-Adrenoceptor Agonists and Relevant Hyperlactatemia: Systematic Review and Meta-Analysis
Authors: Liedtke Alina G. , Lava Sebastiano A. G. , Milani Gregorio P. , Agostoni Carlo , Gilardi Viola , Bianchetti Mario G. , Treglia Giorgio , Faré Pietro B.
Published: December 2019

Selective ß2-agonists have been imputed as potential cause of l-hyperlactatemia since the 1970s. To document the prevalence of hyperlactatemia associated with selective ß2-agonists and to investigate the predisposing factors, we searched for published articles until April 2019 pertaining to the interplay of administration of selective ß2-agonists and circulating l-lactic acid in the Excerpta Medica, Web of Science, and the U.S. National Library of Medicine databases. Out of the 1834 initially retrieved records, 56 articles were included: 42 papers reporting individual cases, 2 observational studies, and 12 clinical trials. Forty-seven individual patients receiving a selective ß2-agonist were found to have l-lactatemia ≥5.0 mmol/L, which decreased by ≥3.0 mmol/L or to ≤2.5 mmol/L after discontinuing (N = 24), reducing (N = 17) or without modifying the dosage of the selective ß2-agonist (N = 6). Clinical trials found that l-lactic acid significantly increased in healthy volunteers administered a ß2-agonist. l-lactatemia ≥5.0 mmol/L was observed in 103 (24%) out of 426 patients with asthma or preterm labor managed with a selective ß2-agonist and was more common in patients with asthma (30%) than in premature labor (5.9%). A significant relationship was also noted between l-lactate level and intravenous albuterol dose or its circulating level. In conclusion, relevant l-hyperlactatemia is common on high dose treatment with a selective ß2-agonist.