bluuebunny/crossref_metadata_2025 huggingface dataset:
Decrease in Membrane Fluidity and Traction Force Induced by Silica-Coated Magnetic Nanoparticles
Authors: Shin Tae Hwan , Ketebo Abdurazak Aman , Lee Da Yeon , Lee Seungah , Kang Seong Ho , Basith Shaherin , Manavalan Balachandran , Park Sungsu , Lee Gwang
Published: November 2020

Background Nanoparticles are being used increasingly due to their unique physical and chemical properties and small size. It is well-known that nanoparticles cause side effects, however their biophysical assessment remains challenging. We addressed this issue by investigating the effects of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate [MNPs@SiO2(RITC)] on the biophysical aspects, such as membrane fluidity and traction force of human embryonic kidney 293 (HEK293) cells. We further extended our understanding on the biophysical effects of nanoparticles on cells using a combination of metabolic profiling and transcriptomic network analysis. Results Overdose (1.0 μg/µl) treatment of MNPs@SiO2(RITC) induced lipid peroxidation and decreased membrane fluidity in HEK293 cells. During membrane damage, HEK293 cells were morphologically shrunk and aspect ratio of the cells were significantly decreased upon MNPs@SiO2(RITC) treatment. Each of traction force (measured in micropillar) was found to be increased, thereby increasing the total traction force in MNPs@SiO2(RITC)-treated HEK293 cells. Due to the reduction in membrane fluidity and elevation of traction force, velocity of the cell movement was significantly decreased in MNPs@SiO2(RITC)-treated HEK293 cells. Moreover, intracellular ATP also decreased in a dose dependent manner upon MNPs@SiO2(RITC) treatment. To understand the biophysical changes in cells, we analysed transcriptome and metabolic profiles and generated metabotranscriptomics network. The network showed relationships among peroxidation of lipid, focal adhesion, cell movement, and related genes and metabolites. Furthermore, in silico prediction of the network showed increment in the peroxidation of lipid and suppression of focal adhesion and cell movement.Conclusion Taken together, our results demonstrate that overdosage of MNPs@SiO2(RITC) impairs cellular movement, followed by changes in the biophysical properties of cells, thus highlighting the need for biophysical assessment of nanoparticle-induced side effects.
Conformer-Dependent VUV Photodynamics and Chiral Asymmetries in Pure Enantiomers of Gas Phase Proline
Authors: Hadidi Rim , Bozanic Dusan , Ganjitabar Hassan , Garcia Gustavo , Powis Ivan , Nahon Laurent
Published: November 2020

Proline is a unique amino-acid, with a secondary amine fixed within a pyrrolidine ring providing specific structural properties to proline-rich biopolymers. Gas-phase proline possesses four main H-bond stabilized conformers differing by the ring puckering and carboxylic acid orientation. The latter defines two classes of conformation, whose large ionization energy difference allows a unique conformer-class tagging via electron spectroscopy. Photoelectron circular dichroism (PECD) is an intense chiroptical effect sensitive to molecular structures, hence theorized to be highly conformation-dependent. Here, besides a conformer-dependant cation fragmentation behaviour, we present experimental evidence of an intense and striking conformer-specific PECD, measured in the VUV photoionization of proline. This finding, combined with theoretical modelling, allows a refinement of the conformational landscape and energetic ordering, that proves inaccessible to current molecular electronic structure calculations. Additionally, astrochemical implications regarding a possible link of PECD to the origin of life’s homochirality are considered in terms of plausible temperature constraints.
Characterization of Stable Hypoxia-Preconditioned Dental Pulp Stem Cells: Implication for Pulp Regeneration
Authors: Zayed Mohammed , Iohara Koichiro , Watanabe Hideto , Ishikawa Mami , Tominaga Michiyo , Nakashima Misako
Published: November 2020

Background: Dental pulp stem cells (DPSCs) have been developed as a potential source of mesenchymal stem cells (MSCs) for regeneration of dental pulp and other tissues. However, further strategies to isolate highly functional DPSCs beyond the colony-forming methods are required. Our clinical study has demonstrated safety and efficacy of DPSCs isolated by G-CSF-induced mobilization and cultured under normoxia (mobilized DPSCs, MDPSCs) for pulp regeneration. It is well known that the oxygen concentration is closely linked to the maintenance of stemness. Thus, in this investigation, hypoxia-preconditioned DPSCs (hpDPSCs) was characterized to develop and improve the clinical utility for regeneration of dental pulp in endodontics.Methods: Colony-forming DPSCs were isolated and preconditioned with hypoxia in a stable closed cultured system and compared with MDPSCs isolated from the individual dog teeth. We examined the proliferation rate, migration potential, anti-apoptotic activity and gene expression of the stem cell markers and angiogenic/neurotrophic factors. Trophic effects of the conditioned medium (CM) were also evaluated. In addition, the expression of immunomodulatory molecules upon stimulation with IFN-γ were investigated. The pulp regenerative potential and transplantation safety of hpDPSCs were further assessed in pulpectomized teeth in dogs by histological and immunohistochemical analyses and by chemistry of blood and urine. tests Results: hpDPSCs demonstrated higher proliferation rate and expression of a major regulator of oxygen homeostasis, HIF-1α, and a stem cell marker, CXCR-4. The direct migratory activity of hpDPSCs in response to G-CSF was significantly higher than MDPSCs. The CM of hpDPSCs stimulated neurite extension. However, there were no changes in angiogenic, migration and anti-apoptotic activities compared with the CM of MDPSCs. The expression of immunomodulatory gene, PTGE was significantly up-regulated by IFN gamma in hpDPSCs compared with MDPSCs. However, no difference in nitric oxide was observed. The regenerated pulp tissue was quantitatively and qualitatively similar in hpDPSC transplants compared with MDPSC transplants in dog teeth. There was no evidence of toxicity or adverse events of the hpDPSC transplantation Conclusions: These results demonstrated that hpDPSCs improved stem cell properties compared to MDPSCs, suggesting their potential clinical utility for pulp regeneration.
Dental Pulp Stem Cells: an Alternative Source of Mesenchymal Stem Cells with Potential Osteogenic Regenerative Capacities
Authors: Mucientes Arkaitz , Herranz Eva , Moro Enrique , González-Corchón Aranzazu , Peña-Soria María Jesús , Pena Pilar , Baudín Carmen , Abasolo Lydia , Rodriguez-Rodriguez Luis , Lamas José Ramón , Fernandez-Gutierrez Benjamin
Published: November 2020

Background: Bone innate ability to repair without scaring is surpassed by major bone damage. Current gold-standard strategies do not achieve a full recovery of the bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells, like mesenchymal stem cells (MSCs), and bioactive ceramic scaffolds, like calcium phosphate-based (CaPs), are promising. Biological properties of the MSCs, including osteogenic potential, are influenced by the tissue source. The aim of this study is to define the MSC source and construct (MSC and scaffold combination) most interesting for its clinical application in the context of bone regeneration.Methods: MSCs of 9 healthy donors were isolated from adipose tissue, bone marrow and dental pulp. MSCs were cultured both on plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate) to compare their biological features: proliferation rate, osteogenic potential, cell viability and activity, ability to colonize the CaPs and ALP activity. Results: iTRAQ results generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. On plastic, MSCs isolated from dental pulp (DPSCs) were the MSCs with the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs are the MSCs with the greatest capacity to colonize bioceramics. Furthermore, results show a trend for DPSCs are the MSCs with the most robust increase in the ALP activity.Conclusion: Based in our results, we propose DPSCs as a suitable MSCs for bone/dental regeneration cell-based strategies.
Clinical Characteristics and Predictors of In-hospital Mortality in Patients with Cardiogenic Shock: Results from the RESCUE Registry
Authors: Yang Jeong Hoon , Choi Ki Hong , Ko Young-Guk , Ahn Chul-Min , Yu Cheol Woong , Chun Woo Jung , Jang Woo Jin , Kim Hyun-Joong , Kim Bum Sung , Bae Jang-Whan , Lee Sang Yeub , Kwon Sung Uk , Lee Hyun-Jong , Lee Wang Soo , Jeong Jin-Ok , Park Sang-Don , Lim Seong-Hoon , Cho Sungsoo , Park Taek Kyu , Lee Joo Myung , Song Young Bin , Hahn Joo-Yong , Choi Seung-Hyuk , Gwon Hyeon-Cheol
Published: November 2020

Background: In the current era of mechanical circulatory support, limited data are available on prognosis of cardiogenic shock (CS) caused by various diseases. We investigated the characteristics and predictors of in-hospital mortality in Korean CS patients.Methods: The RESCUE study is a multi-center, retrospective and prospective registry of patients that presented with CS. Between January 2014 and December 2018, 1,247 patients with CS were enrolled from 12 major centers in Korea. The primary outcome was in-hospital mortality. Results: In-hospital mortality rate was 33.6%. The main causes of shock were ischemic heart disease (80.7%), dilated cardiomyopathy (6.1%), myocarditis (3.2%), and non-ischemic ventricular arrhythmia (2.5%). Vasopressors were used in 1081 patients (86.7%). The most frequently used vasopressor was dopamine (63.4%) followed by norepinephrine (57.3%). An intra-aortic balloon pump was used in 314 patients (25.2%) and extracorporeal membrane oxygenator in 496 patients (39.8%). In multi-variable analysis, age ≥70 years, cardiac arrest at presentation, vasoactive-inotrope score >80, continuous renal replacement therapy, and mechanical ventilator were independent predictors for in-hospital mortality.Conclusions: The in-hospital mortality of CS patients remains high despite the high utilization of mechanical circulatory support. Age, cardiac arrest at presentation, amount of vasopressor, and advanced organ failure were poor prognostic factors for in-hospital mortality.Trial registration: RESCUE registry, Clinicaltrials.gov, NCT02985008, Registered 01 January 2014 - Retrospectively and Prospectively registered https://clinicaltrials.gov/ct2/show/NCT02985008.
Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma Presenting as Suspected Cervical Osseous Metastasis : A Case Report and Literature Review
Authors: Chong A-ri , Kim Kweon-cheon , Hong Ran
Published: November 2020

Background : The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is an uncommon variant of PTC. Although its histologic features are aggressive, its prognostic significance remains controversial. Case summary : Bone scan of 41-year-old woman with a history of breast and thyroid cancers showed suspected cervical osseous metastasis during the previous cancer follow-up. Further, magnetic resonance imaging was recommended. Preoperative fine needle aspiration cytology showed features of thyroid papillary carcinoma and postoperatively, the mass was diagnosed to DSV-PTC showing features of numerous and diffuse calcification and squamous metaplasia. Conclusion : Herein, we describe the pathologic features, including histologic and fine-needle aspiration cytologic features, and prognostic implications through a literature review.
The One With Highest Tumor Proportion Score of Multiple Core Needle Biopsies From the Tumor Can Best Represent PD-L1 Status Estimated by Whole Surgical Specimen in Non-small Cell Lung Cancer
Authors: Sun Wei , Yang Xin , Wang Haiyue , Wu Jianghua , Chen Mailin , Liu Changling , Hu Di , Huang Xiaozheng , Jia Ling , Kang Qiang , Wu Qi , Diao Xinting , Zhou Lixin , Lin Dongmei
Published: November 2020

AIM: The heterogeneity of PD-L1 status between core needle biopsies (CNBs) from one tumor was not well studied before. The current study attempts to find out the best index using multiple core biopsies from one tumor which can better reflect the actual PD-L1 status. METHODS: Random CNB was performed in surgical specimens from 170 consecutive Non-Small Cell Lung Cancer (NSCLC) samples. 51 cases (41 cases with PD-L1 positive and 10 cases with PD-L1 negative) and 216 matched CNBs were analyzed by DAKO 22C3 PharmDx Link 48 Autostainer. The PD-L1 status was compared between the surgical specimens and matched CNBs. RESULTS: The heterogeneity of PD-L1 status between CNBs from one tumor was observed in 56.1% PD-L1 positive cases. Different tumor proportion score (TPS) statistical forms with regard to the highest, mean, median, weighted average TPS, as well as TPS showed by the longest biopsy specimen and the biopsy with most tumor volume were compared. At a cutoff of 1%, the concordance rates were 94.1%, 88.2%, 90.2%, 86.3%, 86.3% and 86.3%; At a cutoff of 50%, the concordance rates were 92.2%, 86.3%, 84.3%, 82.4%, 82.4% and 86.3%, respectively. The CNB with the highest TPS can best represent PD-L1 status estimated by whole surgical specimen.CONCLUSIONS: The highest TPS among the multiple biopsies is a robust evaluation of the PD-L1 status, but not mean TPS, at the 1% and 50% cutoffs.
Nurses’ Perceptions of Medication Administration Safety in Public Hospitals in the Gauteng Province: A Mixed Method Study
Authors: Blignaut Alwiena J , Coetzee Siedine Knobloch , Ellis Suria M , Klopper Hester C
Published: November 2020

Background: This study was carried out to determine factors perceived to impact on medication administration errors and possible solutions to such errors in medical and surgical units of public hospitals in Gauteng Province, South Africa. More data on this challenge to patient health are needed from low- and middle-income countries like South Africa.Methods: A mixed-methods research design with a sequential approach was used. Data were gathered among 683 (n=280) medication administrators using self-report surveys, and 16 (n=15) nursing unit managers using semi-structured individual interviews.Results: Causes of medication error related to communication, human, environmental and medication factors were considered to have a moderate risk. Workload (M=3.39; SD 0.91), stock problems (M=3.18; SD 0.96) and illegible prescriptions (M=3.05; SD 1.09) pose the greatest threats to medication administration safety. Most participants (n=184; 71.1%) agreed that medication errors never or rarely occurred in their units. The majority of respondents graded overall patient safety as excellent or very good (n=161; 61.5%). With regard to safety culture, nurses felt that they are actively attempting to improve medication safety (n=239; 90.5%), that people support one another in the unit (n=216; 80%), and that their procedures and systems are good at preventing errors (n=210; 80.2%). Participants felt that medication administration errors were rarely reported, and the most apparent reason for not reporting medication administration errors was fear and administrative response. Safety culture items were correlated with medication error incidence, grade of overall patient safety and reasons for non-reporting. Qualitative findings supported the quantitative data, adding knowledge, skill and attitude of staff as further threats to medication administration safety. Adherence to protocols, auditing, education and training, collaboration and support, communication, awareness of changes, resource management and time management were identified as possible solutions to medication administration errors.Conclusions: Solutions aimed at mitigating medication errors should be based on causes identified within a specific context. In the Gauteng Province of South Africa, multidisciplinary collaboration and communication; support of nurses by the hospital administration; hospital systems, procedures and initiatives; better resource management and improved pharmacological training could be seen as the foundation for improved medication administration safety.
Fabrication and characterization of keratin-starch bio-composite film from chicken feather waste and ginger starch
Authors: oluba olarewaju , Obi Chibugo F. , Akpor Oghenerobor B. , Ojeaburu Samuel I. , Adebiyi Feyikemi D. , Adediran Adeolu A. , Oki Makanjuola
Published: November 2020

Background: The disposal of chicken feather through burning or burying is not environmentally compliant due to the accompanying release of greenhouse gas and underground water contamination. Thus, the transformation of this bio-waste into a bio-composite film is considered not only sustainable strategy for disposal of these solid wastes but also an attractive alternative to developing an efficient nanostructure biomaterial from renewable bio resource.Methods: In the present study keratin extracted from chicken feather waste in combination with ginger starch were fabricated into a bio-composite film. The fabricated bio-composite films were characterized, using different analytical techniques.Results: The physicochemical characteristics of ginger starch showed a moisture content of 33.8%, pH of 6.21, amylose and amylopectin contents of 39.1% and 60.9%, respectively. The hydration capacity of the starch was 132.2% while its gelatinization temperature was 65.7 oC. Physical attributes of the bio-composite film, such as surface smoothness and tensile stress increased significantly (p < 0.05) with increasing keratin content, while transparency, solubility significantly (p < 0.05) decreased with increasing keratin level. The various blends of the bio-composite films decayed by over 50% of the original mass after 12 days of complete burial in soil.Conclusion: Based on the results obtained in this study, the addition of keratin to starch bio-composite showed improvement in mechanical properties, such as tensile stress and surface smoothness. The bio-composite film exhibited appropriate stability in water, although future study showed be carried out to evaluate its thermal stability. Nonetheless, the fabricated keratin-starch bio-composite showed desirable characteristics that could be optimized for industrial applications.
Effects of zoledronic acid combined with metformin on bones of DB/DB mice
Authors: Yang Xingyao , Zhao Wen , Ma Wenjie , Yin Xin , Lin Yanshui
Published: November 2020

Background

Diabetic patients are prone to osteoporosis. Both zoledronic acid and metformin have certain anti-osteoporotic effects.Here we explore the anti-osteoporotic effect of the combination of two drugs.
Methods

12-week-old DB/DB mice were divided into DB/DB group, zoledronic acid group,metformin group and zoledronic acid combined with metformin group, WT mice were treated as WT group alone. The mice were killed after ten weeks. Then using Micro-ct to scan the tibia and stain the contralateral lower limbs with HE.
Results

First, we find that the body weight of DB/DB mice treated with metforminre stable and their blood glucose reduce.Second, after HE staining,it is observed under light microscope that there are a large number of adipocytes, few bone trabeculae, few osteoblasts and osteoclasts in the bone marrow cavity in the DB/DB group compared with the WT group, while the number of bone trabeculae in the combined treatment group is higher than that in the zoledronic acid group or metformin group, and a large number of blood cells, blood vessels and adipocytes are found in the bone marrow cavity of the combined drug group compared with the zoledronic acid group. Last, the results of Micro-ct present that, comparing with the DB/DB group and the metformin group,SMI is significantly different(P < 0.05);comparing with the DB/DB group and the zoledronic acid group,Tb.N,Tb.Sp,Conn.D and SMI are significantly different(P < 0.05);BV/TV, Conn.D, SMI, BMD, Tb.N and Tb.Sp in the combination treatment group are significantly difference than those in the DB/DB group(P < 0.05).
Conclusion

In term of the bone mass lose of DB/DB mice, the treatment of the zoledronic acid combined with metformin outperforms that using the zoledronic acid or metformin only.
Re-Appraisal Learning Curve of Laparoscopic Roux-En Y Gastric Bypass: Results of One Hundred and Eight Cases From A Low Volume Unit
Authors: Lo Hung Chieh , Wu Sheng-Mao
Published: November 2020

Background The study aim was to reevaluate the learning curve of laparoscopic Roux-en Y gastric bypass (LRYGB) in the modern era considering a single surgeon’s experience.Methods Except those with body mass index (BMI) >50 kg/m2 needs further discussion; all other patients who met the regional criteria and underwent primary LRYGB were retrospectively enrolled. Those who underwent surgery in 2016-17, 2018 and 2019 by a single surgeon with 10+ years of laparoscopic experience were assigned to groups A, B and C, respectively. Patient demographics and 30-day outcome data, including operation time, length of stay (LOS), emergency room visits, readmission, and reoperation, were compared between groups.Results One hundred and eight patients met the inclusion criteria; 36, 38, and 34 patients were assigned to groups A, B and C, respectively. There were no differences in age, sex distribution or common comorbidities between groups, except group B had a lower BMI (35.1 kg/m2 vs. 37.0 kg/m2) and a higher rate of hypertension (44.7% vs. 22.2%) than group A. The operation time was markedly reduced (96.1 min and 114.9 min, respectively), and the LOS was shortened (2.2 days and 2.9 days, respectively) in group B compared to group A and remained stationary in group C, with no further reduction in 30-day complications.Conclusion The learning process for LRYGB can be shortened to approximately 30 cases if conducted selectively and by experienced laparoscopic surgeons. Further follow-up is required to verify the long-term safety and its applicability to other patient subgroups.
Outpatient care in acute and prehospital emergency medicine by emergency medical and patient transport service over a 10-year period: a retrospective study based on dispatch data from a German emergency medical control center (OFF-RESCUE)
Authors: Schehadat Marc S. , Scherer Guido , Groneberg David A. , Kaps Manfred , Bendels Michael H.K.
Published: November 2020

BackgroundThe number of operations by the German emergency medical service almost doubled between 1994 and 2016. The associated expenses increased by 380 % in a similar period. Operations with treatment on-site, which retrospectively proved to be misallocated (OFF-Missions), have a substantial proportion of the assignment of the emergency medical service (EMS). Besides OFF-Missions, operations with patient transport play a dominant role (named as ON-Missions). The aim of this study is to work out the medical and economic relevance of both operation types.MethodsThis analysis examined N=819,780 missions of the EMS and patient transport service (PTS) in the catchment area of the emergency medical control center (EMCC) Bad Kreuznach over the period from 01/01/2007 to 12/31/2016 in terms of triage and disposition, urban-rural distribution, duration of operations and economic relevance (p<.01).Results53.4 % of ON-Missions are triaged with the indication non-life-threatening patient transport; however, 63.7 % are processed by the devices of the EMS. Within the OFF-Mission cohort, 78.2 % and 85.8 % are triaged or dispatched for the EMS. 74 % of all ON-Missions are located in urban areas, 26 % in rural areas; 81.3 % of rural operations are performed by the EMS. 66 % of OFF-Missions are in cities. 93.2 % of the remaining 34 % of operations in rural locations are also performed by the EMS. The odds for both ON- and OFF-Missions in rural areas are significantly higher than for PTS (ORON 3.6, 95 % CI 3.21-3.30; OROFF 3.18, 95 % CI 3.04-3.32). OFF-Missions last 47.2 minutes (SD 42.3; CI 46.9-47.4), while ON-Missions are processed after 79.7 minutes on average (SD 47.6; CI 79.6-79.9). ON-Missions generated a turnover of more than € 114 million, while OFF-Missions made a loss of almost € 13 million.ConclusionsThis study particularly highlights the increasing utilization of emergency devices; especially in OFF-Missions, the resources of the EMS have a higher number of operations than PTS. OFF-Missions cause immensely high costs due to misallocations from an economic point of view. Appropriate patient management appears necessary from both medical and economic perspective, which requires multiple solution approaches.
Cadmium Stabilization by Sewage Sludge Incineration Ash
Authors: Lyu Zhong , Meng Fanling , Tang Yuanyuan , Shih Kaimin
Published: November 2020

Cadmium (Cd), as a common ingredient in the production process of nickel cadmium batteries, can lead to functional disorder in kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Previous studies have shown that cadmium can be stabilized in ceramic systems using clay as precursor, but the excessive exploitation of nonrenewable clay resources has caused great concerns. Hence, it is essential to find alternatives to substitute nonrenewable clay minerals. Sewage sludge incineration residues, with oxides of aluminum and silicon as major component, have attracted much attention because of the potential resource utilization. In this study, CdO and CdNO 3 was used to simulate cadmium-bearing industrial waste, and the stabilization of cadmium was achieved in ceramic matrix provided by the residues of sewage sludge incineration. Through a 2-hour sintering procedure at temperatures ranging from 800°C to 1000°C, cadmium was found to be incorporated into CdAl 2 Si 2 O 8 . The leachability of cadmium significantly declined in sintered samples when extracted in acidic environment. Meanwhile, samples that were pressed into pellets showed better cadmium stabilization efficiency, compared with powder samples. Therefore, this study suggests a promising technique to stabilize cadmium by the utilization of sewage sludge incineration residues as ceramic precursors. The success implementation of current study will further reduce the environmental burden caused by the release of heavy metals from industrial waste. Moreover, the recycling of sewage sludge incineration residues can be realized, and a waste-to-resource strategy is expected.
Mild thrombocytopenia indicating maternal organ damage in pre-eclampsia: a cross-sectional study
Authors: Mayama Michinori , Morikawa Mamoru , Yamada Takashi , Umazume Takeshi , Noshiro Kiwamu , Nakagawa Kinuko , Saito Yoshihiro , Chiba Kentaro , Kawaguchi Satoshi , Watari Hidemichi
Published: November 2020

BackgroundCurrently, there is a disagreement between guidelines regarding platelet count cut-off values as a sign of maternal organ damage in pre-eclampsia; the American College of Obstetricians and Gynecologists guidelines state a cut-off value of <100× 109/L; however, the International Society for the Study of Hypertension in Pregnancy guidelines specify a cut-off of <150 × 109/L. We evaluated the effect of mild thrombocytopenia: platelet count <150 × 109/L and ≥100 × 109/L on clinical features of pre-eclampsia to examine whether mild thrombocytopenia reflects maternal organ damage in pre-eclampsia. MethodsA total of 264 women were enrolled in this study. Participants were divided into three groups based on platelet count levels at delivery: normal, ≥150 × 109/L; mild thrombocytopenia, <150 × 109/L and ≥100 × 109/L; and severe thrombocytopenia, <100 × 109/L. Risk of severe hypertension, utero-placental dysfunction, maternal organ damage, preterm delivery, and neonatal intensive care unit admission were analyzed based on platelet count levels. Adjusted relative risk were calculated with a Poisson regression analysis with a robust error. ResultsPlatelet counts indicated normal levels in 189 patients, mild thrombocytopenia in 51 patients, and severe thrombocytopenia in 24 patients. The adjusted risk ratios of severe thrombocytopenia were 2.11 [95% confidence interval, 1.61–2.77] for maternal organ damage except thrombocytopenia, 1.24 [1.01–1.53] for preterm delivery <34 gestational weeks, and 1.16 [1.02–1.32] for neonatal intensive care unit admission. On the other hand, the adjusted risk ratios of mild thrombocytopenia were 1.06 [0.86–1.30] for severe hypertension, 1.17 [0.74–1.83] for utero-placental dysfunction, 0.96 [0.41–2.24] for maternal organ damage except thrombocytopenia, 0.89 [0.60–1.31] for preterm delivery <34 gestational weeks, and 0.96 [0.75–1.23] for neonatal intensive care unit admission. ConclusionsMild thrombocytopenia was not related with severe features of pre-eclampsia and would not be suitable as a sign of maternal organ damage.
Mitochondrial Transplantation Improves Stroke-Induced Brain Injury: Possible Involvement of Selective Component Recombination
Authors: Xie Qiang , Zeng Jun , Xu Feng , Zheng Yongtao , Li Tianwen , Ren Junwei , Chen Kezhu , Zhang Quan , Xie Rong , Zhu Jianhong
Published: November 2020

Background: Ischemic stroke results in high morbidity and mortality, and mitochondrial dysfunctions play a crucial role in the associated pathological process. Although exogenous mitochondria were used to treat ischemic stroke-induced brain injury, its effects and related mechanisms remain poorly understood, as is the fate of exogenous mitochondria during/after internalization by targeted cells. Methods: The mitochondrial morphology, membrane potential, DNA copy number, mitochondrial stress, metabolic characteristics and tumorigenicity of mNSCs and Neuro-2a cells were evaluated. Hypoxia/reoxygenation-induced cell injury was performed, and after mitochondrial supplementation, the viability, ROS levels, apoptosis and transcriptomic changes were assessed by CCK-8, DCHF-DA probes, flow cytometry, WB and next-generation sequencing analyses. The fate of exogenous mitochondria was further explored using fluorescent dyes and fusion protein analyses during/after internalization by targeted cells. Rat tMCAO models were generated using a suture-occluded method, and at 24 h after mitochondrial transplantation, behavioral changes and brain infarction areas were estimated by multiple score scales and TTC staining, respectively. Results: In this research, we found that mitochondria of Neuro-2a cells had some notable differences compared to that of mNSCs on mitochondrial membrane potential, DNA copy number, stress response and metabolic characteristics, but their shapes were similar and were both no tumorigenicity. Exogenous mitochondrial treatment could increase the cellular viability in an oxygen-dependent pattern, decrease the cellular ROS generation and apoptosis, and alter the transcriptomic characteristics after subjected to hypoxia/reoxygenation in vitro. Selective component recombination might occur during/after internalization of exogenous mitochondria by host cells and was observed with mitochondrial fluorescent dyes and engineered fusion protein. Moreover, mitochondrial transplantation could significantly improve tMCAO-induced rat neurobehavioral deficiency and brain infarction. Conclusions: The results of our present study offer a promising therapeutic strategy for ischemia/reperfusion-induced brain injury and provide preliminary insights regarding the effects and fate of exogenous mitochondria during/after being internalized into host cells.
Pharmacokinetics and Bioequivalence Study of Two Ciprofloxacin Hydrochloride Tablets in Chinese Healthy Volunteers Under Fasting and Fed Conditions: A Randomized, Open-Label, Two-Formulation, Two-Sequence, Two-Period, Single-Dose Crossover Study.
Authors: Qin Fei , Wang Gan-Mi , Huang Jin-Ying , Wu Jia-Rong , Song Wen-Jie , Deng Jun , Xiao Ying , Wang Jian-Song , Zhu Ke-Wei
Published: November 2020

BackgroundCiprofloxacin is a broad-spectrum fluoroquinolone antibiotic which is active against a wide range of Gram-positive and Gram-negative bacteria. The study mainly aimed to determine the bioequivalence of two branded ciprofloxacin hydrochloride tablets (250 mg) under the fasting and fed conditions.MethodsThe study was carried out in 48 healthy Chinese subjects under fasting and fed conditions with a randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover design. In each period of the study, the subjects were assigned to receive a single oral dose of 250 mg of ciprofloxacin hydrochloride. Blood samples were collected from an hour before dosing to 36 h after administration with 16 time points in total. The bioequivalence analysis was performed after ln-transformation of the ciprofloxacin pharmacokinetic parameters including maximum concentration (Cmax), area under the plasma concentration–time curve from time 0 to time t (AUC0-t), area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞). Two formulations are considered bioequivalent if the 90% confidence intervals (CIs) for the test/reference geometric mean ratios (GMRs) for the ln-transformed pharmacokinetic parameters fall within the standard acceptance range of 80% – 125%. ResultsIn total of 48 subjects were enrolled in the fasting and fed studies, and one of the subjects was excluded before the administration. In the fasting study, the 90% CIs for the test/reference GMRs of the ln-transformed data for Cmax, AUC0–t, and AUC0–∞ were 85.41% to 100.97%, 95.40% to 100.27%, and 95.48% to 100.30%, respectively. For the fed study, the 90% CIs for the test/reference GMRs of the ln-transformed data for Cmax, AUC0–t, and AUC0–∞ were 90.15% to 113.75%, 99.10% to 103.77% and 99.11% to 103.80%, respectively. A total of 8 of 47 subjects experienced AEs in the fasting and fed studies.ConclusionsIn the study, the generic (test) product of ciprofloxacin hydrochloride 250 mg was bioequivalent to the innovator (reference) product after a single oral dose administration under the fasting and fed conditions. Both two brands of ciprofloxacin tablets were safe and well tolerated.Trial registrationThe clinical trial was registered at Center for the Drug Evaluation of the National Medical Products Administration (registration number: CTR20171152; date of registration：September 25, 2017; http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml).
Beauty, the feeling
Authors: Brielmann Aenne , Nuzzo Angelica , Pelli Denis
Published: November 2020

Many philosophers and psychologists have made claims about the feelings in an experience of beauty. Here, we test how well these claims match the feelings that people report while looking at an image or listening to music that is beautiful to them, or recalling a personal experience of beauty. We conducted ten experiments (total n = 851) spanning three nations (US, UK, and India). Across nations and modalities, we find that top-rated beauty experiences are strongly characterized by six dimensions: intense pleasure, an impression of universality, the wish to continue the experience, perceived harmony in variety, exceeding expectation, and meaningfulness. Other frequently proposed beauty characteristics — like surprise, desire to understand, and mind wandering — are uncorrelated with feeling beauty. When explicitly asked, participants in all countries report that beauty is closely related to pleasure, found in nature rather than art, influenced by mood, and a form of communication. A remembered beautiful experience was typically active and social, like a family holiday, quite unlike the passive solitary appraisal of art emphasized in aesthetics. Our data align well with Kant (r = 0.74) and psychological theories that emphasize pleasure, and reject theories that emphasize information seeking. These six dimensions characterizing how individuals feel beauty emerge from the reports of hundreds of people seeing, hearing, or remembering something beautiful to them.
Homegarden Agroecosystems Managed by Salar People on Qinghai-Tibet Plateau
Authors: Zhu Mingjing , La Ben , Luo BinSheng , Chen Ruijie , Liu Fenggui , Long Chunlin
Published: November 2020

Background: Salar is a Turkic-speaking Islamic ethnic group in China, who live primarily in Xunhua Salar Autonomous County, Qinghai-Tibet Plateau. Salar people have engaged in agriculture especially skilled in horticulture and their homegardens (HGs)　management. They are regarded as the first people on Qinghai-Tibet plateau to practice horticulture, especially manage their HGs, which are traditional farming systems and also supplementary food production systems. Traditional knowledge of Salar people associated with their homegardens always contributes in livelihood, food security, ornamental value and biodiversity conservation. The cultivation of different plants in HGs for self-sufficiency has a long tradition in China’s rural area especially in some mountainous areas. However, Salar people’s traditional HGs have not been described. The present paper aims to report the features of Salar’s HGs focusing on agrobiodiversity and its important role. Methods: The methods used in this work included literature study, semi-structured interviews, participatory observation, and panel consultation. A total of 60 households in each 9 villages were surveyed. In each household there are 4-12 family members, aged from 20 to 86 years old. The homestead size is between 200 and 1200 m2. Plant species cultivated in homegardens were identified according to Flora of China. Based on comprehensive survey of Salar people’s HGs and related background data, we identified and characterized the most important functions and ecosystem services provided by HGs of Salar people.Results: According to primary production systems, there are 4 different types of HGs, including ornamental focus, product focus, dual-purpose and multi-purpose. In total 108 (excluding weeds and bonsai) plant species were found in HGs of study area, within 43 families. The most important and frequency plants are Rosa chinensis, Armeniaca vulgaris, and Capsicum annuum. The average number of plants varied from 4 to 32 species in each homegarden in three investigated townships. HGs of Salar people contain 8 different functions and we identify and characterize 16 services: 2 regulating services, 2 support services, 4 production services and 8 culture services.Conclusion: This paper reveals the floristic diversity of HGs of Salar communities. Meanwhile, it provides basic information for homegarden agroecosystem of Salar people. Ecosystem services and function research suggested that Salar people’s homegarden agroecosystem provide ecosystem services mainly related to supply services and culture services. Salar people’s HGs are important food supplement, aesthetics and cultural spaces where knowledge related to agricultural practices is transmitted and through which households may improve their leisure and livelihoods.
Traditional Knowledge and Use of Rock Pools in the Brazilian Caatinga: Memory and Identity in Temporary Ecosystems
Authors: Barbosa Luciana Gomes , Santos João Paulo de Oliveira , Silva Kelly Dayane Pereira da , Silva Núbia da , Santos Ismael Romão dos , Lucena Reinaldo Farias Paiva de
Published: November 2020

BackgroundMemory is a collective ownership based on facts and past events. Aristotle and Agostinho were the first philosophers to investigate it, including the dimensions of time and memory inhabited by man. Northeastern Brazil has a rich cultural history linked to water scarcity in the region, one of the main limiting factors to the development of rural populations. Among alternative sources, temporary ecosystems known as rock pools have been used as rainwater storage in arid and semiarid regions around the world. Considering the hypothesis that the arrival of perennial water sources can impact memory transmission between generations, this study aimed to analyze the popular knowledge about rock pools, a traditional and ancient water source.MethodsInformation about the use and management of rock pools in the Brazilian semiarid region was collected by interviewing residents from a small city near an inselberg. The interviews presented specific questions about the structure, characteristics, traditional knowledge, use and management of rock pools. During sampling, 20 rock pools were visited by two key informants, i.e., those with more experience and knowledge about these ecosystems.ResultsOur results identified that the use and management of rock pools were reduced after the Brazilian government implemented the One Million Cisterns Project. Therefore, despite the historical relevance of these water bodies, their uses were forgotten by most of the inhabitants and those from neighboring locations, remaining for domestic use.ConclusionsResults about traditional knowledge indicated that the generation interviewed still remembers such method. However, with the presence of cisterns, the transmission of traditional knowledge about rock pools has decreased between the families and generations, presenting a serious social risk for a region characterized by extreme and prolonged droughts.
Accounting for Confounding by Time, Early Intervention Adoption, and Time-Varying Effect Modification in the Design and Analysis of Stepped-Wedge Designs: Application to a Proposed Study Design to Reduce Opioid-Related Mortality
Authors: Rennert Lior , Heo Moonseong , Litwin Alain H , De Gruttola Victor
Published: November 2020

Background: Stepped-wedge designs (SWDs) are currently being used in the investigation of interventions to reduce opioid-related deaths in communities located in several states. However, these interventions are competing with external factors such as newly initiated public policies limiting opioid prescriptions, media awareness campaigns, and COVID-19 social distancing mandates. Furthermore, control communities may prematurely adopt components of the intervention as they become available. The presence of time-varying external factors that impact study outcomes is a well-known limitation of SWDs; common approaches to adjusting for them make use of a mixed effects modeling framework. However, these models have several shortcomings when external factors differentially impact intervention and control clusters. Methods: We discuss limitations of commonly used mixed effects models in the context of proposed SWDs to investigate interventions intended to reduce opioid-related mortality, and propose extensions of these models to address these limitations. We conduct an extensive simulation study of anticipated data from SWD trials targeting the current opioid epidemic in order to examine the performance of these models in the presence of external factors. We consider confounding by time, premature adoption of components of the intervention, and time-varying effect modification— in which external factors differentially impact intervention and control clusters. Results: In the presence of confounding by time, commonly used mixed effects models yield unbiased intervention effect estimates, but can have inflated Type 1 error and result in under coverage of confidence intervals. These models yield biased intervention effect estimates when premature intervention adoption or effect modification are present. In such scenarios, models incorporating fixed intervention-by-time interactions with an unstructured covariance for intervention-by-cluster-by-time random effects result in unbiased intervention effect estimates, reach nominal confidence interval coverage, and preserve Type 1 error. Conclusions: Mixed effects models can adjust for different combinations of external factors through correct specification of fixed and random time effects; misspecification can result in bias of the intervention effect estimate, under coverage of confidence intervals, and Type 1 error inflation. Since model choice has considerable impact on validity of results and study power, careful consideration must be given to choosing appropriate models that account for potential external factors.
AdipoR2 Inhibits Human Glioblastoma Cells Growth Through the AMPK/mTOR Pathway
Authors: Jie Chen , Xuan Wang , DongFeng Han , MaoHua Ding , Bo Wang , Fei Sun , Hao Zhang , DeHua Jiang
Published: November 2020

Background: AdipoR2belongs to seven transmembrane domains receptor family, which has been shown to have played an important role in the development of human tumor, but the underlying mechanisms are poorly understood. In this study, we found that AdipoR2 expression correlates with glioma grade. In addition, we also investigated the mechanisms behind the anti-proliferative effects of AdipoR2 in U251 cells (human glioma cell line) using the colony formation assay and WST-8 growth assay. Methods: U251 cell line were cultured in vitro; Western Blotting was used to detect the expression of related proteins; Using Quantitative RT-PCR to detect AdipoR1and AdipoR2 expression; Detection of Cell cycle assay by flow cytometry; The gene expression profiles of glioma samples from CCGA were analyzed by Matlab and GSEA software.Results: We found 648 upregulated genes and 436 downregulated genes correlated with AdipoR2 expression in 158 glioma samples. GSEA analysis suggested that AdipoR2 is a cell cycle–associated gene. Results of flow cytometry analysis indicated that AdipoR2 induced cell cycle G0/G1 arrest in U251 cells. Furthermore, we identified the AMPK/mTOR signaling axis to be involved in AdipoR2-induced cell cycle arrest.Conclusions: Our results suggest that AdipoR2 may represent a novel endogenous negative regulator of GBM cell proliferation. These findings also suggested that AdipoR2may be a promising therapeutic target in GBM patients.
Assessment the Risk Perception of Health Care Workers of Covid-19 Disease
Authors: Samadipour Ezat , Ghardashi Fatemeh , Zardosht Roghayeh , Borzoee Fatemeh , Navipour Elham
Published: November 2020

Background and Objectives: The emergent Covid-19 disease with conspicuous prevalence is putting the healthcare workers' job security at risk. The preventive behaviors in every individual have a close relationship with his/her risk perception of the risk factor. Hence the present study has been undertaken aiming at determining the Iranian healthcare workers' risk perception of the Covid-19 disease and the relevant effective factors. Materials and Methods: This anonymous online survey was conducted in March-April, 2020 using targeted snowball sampling among the Iranian healthcare workers. The data was collected via online-social networks using a questionnaire containing demographical specifications (5 questions), risk perceptions (20 questions), with five sub-scales including cognitive, cultural, political, social and emotional factors. Data analysis was performed using SPSS v.16 software.Results: From 165 participants, the youth (20-49 years of age) with 84% and the females with 60% constituted the majority of participants. The average risk perception score of the healthcare workers was 66.43±8.17. The Spearman correlation coefficient showed the significant direct relationship between the risk perception score and all the sub-scales at 0.01 significance level. The political and cultural factors had the highest correlation with the personnel risk perception (r > 0.75).Conclusion: Health workers did not have an excellent risk perception of the emergent Covid-19 disease. Training seems to be necessary to increase employee risk perception and requires more extensive studies.