bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of endothelial and glycocalyx injury biomarkers with fluid administration, development of acute kidney injury, and 90-day mortality: data from the FINNAKI observational study
Authors:   the FINNAKI Study Group, Inkinen Nina , Pettilä Ville , Lakkisto Päivi , Kuitunen Anne , Jukarainen Sakari , Bendel Stepani , Inkinen Outi , Ala-Kokko Tero , Vaara Suvi T.
Published: September 2019

Background

Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the association of Syndecan-1 (SDC-1), Angiopoetin-2 (Ang-2), soluble thrombomodulin (sTM), vascular adhesion protein-1 (VAP-1) and interleukin-6 (IL-6) with fluid administration and balance among septic critical care patients and their association with development of acute kidney injury (AKI) and 90-day mortality.

Results

SDC-1, Ang-2, sTM, VAP-1 and IL-6 levels were measured at ICU admission from 619 patients with sepsis. VAP-1 decreased (p < 0.001) and IL-6 increased (p < 0.001) with increasing amounts of administered fluid, but other biomarkers did not show differences according to fluid administration. In linear regression models adjusted for IL-6, only VAP-1 was significantly associated with fluid administration on day 1 (p < 0.001) and the cumulative fluid balance on day 5/ICU discharge (p = 0.001). Of 415 patients admitted without AKI, altogether 112 patients (27.0%) developed AKI > 12 h from ICU admission (AKI>12 h). They had higher sTM levels than patients without AKI, and after multivariable adjustment log, sTM level was associated with AKI>12 h with OR (95% CI) of 12.71 (2.96–54.67), p = 0.001). Ninety-day non-survivors (n = 180; 29.1%) had higher SDC-1 and sTM levels compared to survivors. After adjustment for known confounders, log SDC-1 (OR [95% CI] 2.13 [1.31–3.49], p = 0.002), log sTM (OR [95% CI] 7.35 [2.29–23.57], p < 0.001), and log Ang-2 (OR [95% CI] 2.47 [1.44–4.14], p = 0.001) associated with an increased risk for 90-day mortality. Finally, patients who had high levels of all three markers, namely, SDC-1, Ang-2 and sTM, had an adjusted OR of 5.61 (95% CI 2.67–11.79; p < 0.001) for 90-day mortality.

Conclusions

VAP-1 and IL-6 associated with fluid administration on the first ICU day. After adjusting for confounders, sTM was associated with development of AKI after 12 h from ICU admission. SDC-1, Ang-2 and sTM were independently associated with an increased risk for 90-day mortality.
Predictors of successful separation from high-flow nasal oxygen therapy in patients with acute respiratory failure: a retrospective monocenter study
Authors: Rodriguez Maeva , Thille Arnaud W. , Boissier Florence , Veinstein Anne , Chatellier Delphine , Robert René , Le Pape Sylvain , Frat Jean-Pierre , Coudroy Remi
Published: September 2019

Background

High-flow nasal oxygen therapy (HFOT) is a promising first-line therapy for acute respiratory failure. However, its weaning has never been investigated and could lead to unnecessary prolonged intensive-care unit (ICU) stay. The aim of this study is to assess predictors of successful separation from HFOT in critically ill patients. We performed a retrospective monocenter observational study over a 2-year period including all patients treated with HFOT for acute respiratory failure in the ICU. Those who died or were intubated without prior HFOT separation attempt, who were treated with non-invasive ventilation at the time of HFOT separation, or who received HFOT as a preventive treatment during the post-extubation period were excluded.

Results

From the 190 patients analyzed, 168 (88%) were successfully separated from HFOT at the first attempt. Patients who failed separation from HFOT at the first attempt had longer ICU length of stay than those who succeeded: 10 days (7–12) vs. 5 (4–8), p < 0.0001. Fraction of inspired oxygen (FiO2) ≤ 40% and a respiratory rate-oxygenation (ROX) index (calculated as the ratio of SpO2/FiO2 to the respiratory rate) ≥ 9.2 predicted successful separation from HFOT with sensitivity of 85% and 84%, respectively.

Conclusions

FiO2 ≤ 40% and ROX index ≥ 9.2 were two predictors of successful separation from HFOT at the bedside. Prospective multicenter studies are needed to confirm these results.
A robust fusion estimation with unknown cross-covariance in distributed systems
Authors: Wu Duzhi , Hu Aiping
Published: September 2019

An efficient robust fusion estimation (RFE) for distributed fusion system without knowledge of the cross-covariances of sensor estimation errors is suggested. With the hypothesis that the object lying in the intersection of some ellipsoids related to sensor estimations, the robust fusion estimation is designed to be a minimax problem, which is solved by proposing a novel relaxation strategy. Some properties of the RFE are discussed, and numerical simulations are also present to compare the tracking performance of RFE with that of the centralized fusion and CI method. The numerical examples show that the average tracking performance of RFE is slightly better than that of the CI method, and the performance degradation of RFE is acceptable compared with the centralized fusion.
Joint congestion control and resource allocation for energy-efficient transmission in 5G heterogeneous networks
Authors: Liu Jain-Shing , Lin Chun-Hung , Huang Heng-Chih
Published: September 2019

The deployment of small cells with carrier aggregation (CA) is a significant feature of fifth generation (5G) mobile communication systems which could be characterized by the multi-dimensional heterogeneity on their diversified requirements upon different resources. Taking the heterogeneity into account, we consider here a joint optimization problem wherein multiple kinds of resources are concurrently allocated to optimize the system throughput utility while enhancing the network energy efficiency (EE) and maintaining the system stability. Especially, for the high-dimensional non-deterministic polynomial (NP)-hard allocation problem embedded, we conduct a mathematical programming model involving nonlinear integer constraints to seek the long-term stable utility on throughput and introduce an iterative optimal modulation and coding scheme-based (optimal MCS-based) heuristic algorithm as an effective solver. In addition, as data traffic and channel condition will be time-varying in the real world, an admission control based on the Lyapunov technique that requires no prior knowledge on channel information is proposed to reduce the system overhead. Finally, not only the performance bound is derived in theory, but also the numerical experiments are conduced to reveal its characteristics with respect to the system parameter V and the EE requirement.
Improved energy-balanced algorithm for underwater wireless sensor network based on depth threshold and energy level partition
Authors: Feng Pan , Qin Danyang , Ji Ping , Zhao Min , Guo Ruolin , Berhane Teklu Merhawit
Published: September 2019

Considering the insufficient global energy consumption optimization of the existing routing algorithms for Underwater Wireless Sensor Network (UWSN), a new algorithm, named improved energy-balanced routing (IEBR), is designed in this paper for UWSN. The algorithm includes two stages: routing establishment and data transmission. During the first stage, a mathematical model is constructed for transmission distance to find the neighbors at the optimal distances and the underwater network links are established. In addition, IEBR will select relays based on the depth of the neighbors, minimize the hops in a link based on the depth threshold, and solve the problem of data transmission loop. During the second stage, the links built in the first stage are dynamically changed based on the energy level (EL) differences between the neighboring nodes in the links, so as to achieve energy balance of the entire network and extend the network lifetime significantly. Simulation results show that compared with other typical energy-balanced routing algorithms, IEBR presents superior performance in network lifetime, transmission loss, and data throughput.
Iterative positive solutions to a coupled fractional differential system with the multistrip and multipoint mixed boundary conditions
Authors: Zhao Xiaodi , Liu Yuehan , Pang Huihui
Published: September 2019

Using the monotone iterative technique, we investigate the existence of iterative positive solutions to a coupled system of fractional differential equations supplemented with multistrip and multipoint mixed boundary conditions. It is worth mentioning that the nonlinear terms of the system depend on the lower fractional-order derivatives of the unknown functions and the boundary conditions involve the combination of the multistrip fractional integral and the multipoint value of the unknown functions in $[0,1]$
[
0
,
1
]
.
A systematic approach for assessment of renewable energy using analytic hierarchy process
Authors: Budak Gerçek , Chen Xin , Celik Serdar , Ozturk Berk
Published: September 2019

Background

Cities around the world face a great challenge in establishing a long-term strategy for the development of energy alternatives. Previous research tried to identify renewable energy across many different cities. Because each city has unique characteristics in terms of geographic and environmental conditions, population, economic development, and social and political environment, the most sustainable energy source for one city might be the least sustainable for another.

Methods

This research develops and implements a systematic approach to assess renewable energy and identify the energy alternatives for a city using the analytic hierarchy process. The methodology integrates experts’ input and data analytics and helps decision-makers form long-term strategies for renewable energy development.

Results

The decision support system is applied to three cities, Chengdu in China, Eskisehir in Turkey, and Chicago in the United States of America. Results show that improving energy efficiency and development of solar and wind energy are the most preferred energy alternatives whereas nuclear and hydroelectric are the least preferred energy alternatives for these three cities.

Conclusions

The results of this study are in line with decades of research and development in energy alternatives and show a clear direction for the future development of energy alternatives around the world. There are differences in the rankings of energy alternatives for different cities, indicating that it is necessary to apply the decision support system developed in this study to help form customized energy strategies for cities with unique characteristics.
Bacillus sp. probiotic supplementation diminish the Escherichia coli F4ac infection in susceptible weaned pigs by influencing the intestinal immune response, intestinal microbiota and blood metabolomics
Authors: Luise Diana , Bertocchi Micol , Motta Vincenzo , Salvarani Chiara , Bosi Paolo , Luppi Andrea , Fanelli Flaminia , Mazzoni Maurizio , Archetti Ivonne , Maiorano Giuseppe , Nielsen Bea K. K. , Trevisi Paolo
Published: September 2019

Background

Probiosis is considered a potential strategy to reduce antibiotics use and prevent post-weaning diarrhea (PWD). This study investigated the effect of Bacillus amyloliquefaciens DSM25840 or Bacillus subtilis DSM25841 supplementation on growth, health, immunity, intestinal functionality and microbial profile of post-weaning pigs after enterotoxigenic E. coli (ETEC) F4 challenge.

Methods

Sixty-four post-weaning piglets (7748 g ± 643 g) were randomly allocated to four groups: control basal diet (CO); CO + 1.28 × 106 CFU/g of B. amyloliquefaciens (BAA); CO + 1.28 × 106 CFU/g feed of B. subtilis (BAS); CO + 1 g colistin/kg of feed (AB). At day (d) 7, animals were challenged with 105 CFU/mL of ETEC F4ac O149 and then followed for fecal score and performance until d 21. Blood was collected at d 6, d 12 and d 21 for immunoglobulins, at d 8 for acute phase proteins, at d 8 and d 21 for metabolomics analysis. Jejunum was sampled for morphometry, quantification of apoptosis, cell proliferation, neutral and acid mucine and IgA secretory cells, and microarray analysis at d 21. Jejunum and cecum contents were collected for microbiota at d 21.

Results

AB and BAS reduced the fecal score impairment compared to CO (P < 0.05) at d 14. Body weight (BW), average daily weight gain (ADWG), average daily feed intake (ADFI) and gain to feed ratio (G:F) did not differ between Bacillus groups and CO. AB improved BW at d 7, d 14 and d 21, ADWG ADFI and G:F from d 0 to d 7 (P < 0.05). At d 8, CO had higher plasma arginine, lysine, ornithine, glycine, serine and threonine than other groups, and higher haptoglobin than AB (P < 0.05). At d 21, CO had lower blood glycine, glutamine and IgA than BAS. Morphology, cells apoptosis and mucins did not differ. BAS and AB increased the villus mitotic index. Transcriptome profile of BAS and AB were more similar than CO. Gene sets related to adaptive immune response were enriched in BAA, BAS and AB. CO had enriched gene set for nuclear structure and RNA processing. CO had a trend of higher Enterobacteriaceae in cecum than the other groups (P = 0.06).

Conclusion

Bacillus subtilis DSM25841 treatment may reduce ETEC F4ac infection in weaned piglets, decreasing diarrhea and influencing mucosal transcriptomic profile.
The adipokine vaspin reduces apoptosis in human hepatocellular carcinoma (Hep-3B) cells, associated with lower levels of NO and superoxide anion
Authors: Skonieczna Magdalena , Hudy Dorota , Hejmo Tomasz , Buldak Rafal J. , Adamiec Małgorzata , Kukla Michal
Published: September 2019

Background

Among adipose-derived factors, adipocytokines play roles as hormones and signaling mediators for apoptotic pathway. Among of them, vaspin, regulates the metabolism of adipose tissue itself as an endocrine organ, and stimulates adipocytes to maturation, differentiation, etc. Damaged adipocytes, present in obesity and hepatocellular carcinoma (HCC) respond with over-production of inflammatory cytokines. Such pro-inflammatory stimulation remains under adipokine control. Pro-inflammatory pathways are connected to oxidative stress and apoptosis, reported as co-existing with an elevated level of some adipokines in cancer cell lines. However, some hormones, such as vaspin, reduce apoptosis, have anti-inflammatory and anti-oxidative roles in cancer cell lines.

Methods

Hep-3B cells were cytometrically evaluated under vaspin treatment for reactive oxygen species (ROS) and apoptosiss induction. The statistical significant changes to the untreated controls was calculated by T-tests (indicated at valuep < 0.05).

Results

Here we studied the production of reactive oxygen and nitrogen species in cells of HCC line Hep-3B after vaspin treatment. A decreased level of nitric oxide and superoxide anion 24 h after vaspin addition at 5 ng/ml was correlated with restricted, to the physiological level, apoptosis. A protective role of vaspin was displayed as enhanced cell viability and proliferation, which could be a poor prognostic in liver cancer.

Conclusions

Apoptosis was suppressed after vaspin treatment, together with low levels of nitric oxide and superoxide anions.
RETRACTED ARTICLE: Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice
Authors: Afridi Ruqayya , Khan Ashraf Ullah , Khalid Sidra , Shal Bushra , Rasheed Hina , Ullah Muhammad Zia , Shehzad Omer , Kim Yeong Shik , Khan Salman
Published: September 2019

Background

Poncirin is flavanone derivative (isolated fromPoncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin in murine models of inflammatory pain.

Methods

The analgesic potential of poncirin was evaluated in formalin-, acetic acid-, carrageenan- and Complete Freund’s Adjuvant (CFA)-induced inflammatory pain models in mice. Anti-allodynic and anti-hyperalgesic activities were measured using Von Frey filaments, Randall Selitto, hotplate and cold acetone tests. The serum nitrite levels were determined using Griess reagent. The Quantitative Real-time PCR (qRT-PCR) was performed to assess the effect of poncirin on mRNA expression levels of inflammatory cytokines and anti-oxidant enzymes.

Results

Intraperitoneal administration of poncirin (30 mg/kg) markedly reduced the pain behavior in both acetic acid-induced visceral pain and formalin-induced tonic pain models used as preliminary screening tools. The poncirin (30 mg/kg) treatment considerably inhibited the mechanical hyperalgesia and allodynia as well as thermal hyperalgesia and cold allodynia. The qRT-PCR analysis showed noticeable inhibition of pro-inflammatory cytokines (mRNA expression levels of TNF-α, IL-1β and IL-6) (p < 0.05) in poncirin treated group. Similarly, poncirin treatment also enhanced the mRNA expressions levels of anti-oxidant enzymes such as transcription factor such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) (p < 0.05), heme oxygenase (HO-1) (p < 0.05) and superoxide dismutase (SOD2) (p < 0.05). Chronic treatment of poncirin for 6 days did not confer any significant hepatic and renal toxicity. Furthermore, poncirin treatment did not altered the motor coordination and muscle strength in CFA-induced chronic inflammatory pain model.

Conclusion

The present study demonstrated that poncirin treatment significantly reduced pain behaviors in all experimental models of inflammatory pain, suggesting the promising analgesic potential of poncirin in inflammatory pain conditions.
Study on firing temperature of the Song Dynasty (960–1279AD) greenish-white porcelain in Guangxi, China by thermal expansion method
Authors: Tong Yongdong , Wang Changming
Published: September 2019

The original firing temperatures of porcelain pieces unearthed from Tengxian Zhonghe kiln, Rongxian Chengguan kiln, Beiliu Lingdong kiln and Guiping Xishan kiln from the Song Dynasty (960–1279AD) of Guangxi were preliminarily studied by thermal expansion method. The experiment results show that the average firing temperature of Zhonghe kiln is 1186 °C (standard deviation 59 °C), the firing temperature relatively concentrated and low. The average firing temperature of Chengguan kiln is 1233 °C (standard deviation 46 °C), with the majority above 1200 °C, indicating that the kiln had a high and concentrated firing temperature. The average firing temperature of Lingdong kiln is 1250 °C (standard deviation 87 °C), the firing temperature are in a broad spectrum. The firing temperatures of Xishan kiln are mostly over 1300 °C (average 1307 °C, standard deviation 75 °C), which are generally considered very high, and the highest one it can go up to 1456 °C, which is the highest firing temperature of ancient Chinese ceramics known to date. Compared with the firing temperature of porcelain in other regions of China in Song Dynasty, it can be concluded that the high-temperature technology of Guangxi porcelain kilns was equal to or even advanced than other kilns. In the light of these findings, we conclude that the ancient Guangxi region of China did not lag behind the central plains in terms of ceramic firing technology and culture.
Construction of gene causal regulatory networks using microarray data with the coefficient of intrinsic dependence
Authors: Liu Li-yu Daisy , Hsiao Ya-Chun , Chen Hung-Chi , Yang Yun-Wei , Chang Men-Chi
Published: September 2019

Background

In the past two decades, biologists have been able to identify the gene signatures associated with various phenotypes through the monitoring of gene expressions with high-throughput biotechnologies. These gene signatures have in turn been successfully applied to drug development, disease prevention, crop improvement, etc. However, ignoring the interactions among genes has weakened the predictive power of gene signatures in practical applications. Gene regulatory networks, in which genes are represented by nodes and the associations between genes are represented by edges, are typically constructed to analyze and visualize such gene interactions. More specifically, the present study sought to measure gene–gene associations by using the coefficient of intrinsic dependence (CID) to capture more nonlinear as well as cause-effect gene relationships.

Results

A stepwise procedure using the CID along with the partial coefficient of intrinsic dependence (pCID) was demonstrated for the rebuilding of simulated networks and the well-known CBF-COR pathway under cold stress using Arabidopsis microarray data. The procedure was also applied to the construction of bHLH gene regulatory pathways under abiotic stresses using rice microarray data, in which OsbHLH104, a putative phytochrome-interacting factor (OsPIF14), and OsbHLH060, a positive regulator of iron homeostasis (OsPRI1) were inferred as the most affiliated genes. The inferred regulatory pathways were verified through literature reviews.

Conclusions

The proposed method can efficiently decipher gene regulatory pathways and may assist in achieving higher predictive power in practical applications. The lack of any mention in the literature of some of the regulatory event may have been due to the high complexity of the regulatory systems in the plant transcription, a possibility which could potentially be confirmed in the near future given ongoing rapid developments in bio-technology.
Inquiry and critical thinking skills for the next generation: from artificial intelligence back to human intelligence
Authors: Spector Jonathan Michael , Ma Shanshan
Published: September 2019

Along with the increasing attention to artificial intelligence (AI), renewed emphasis or reflection on human intelligence (HI) is appearing in many places and at multiple levels. One of the foci is critical thinking. Critical thinking is one of four key 21st century skills – communication, collaboration, critical thinking and creativity. Though most people are aware of the value of critical thinking, it lacks emphasis in curricula. In this paper, we present a comprehensive definition of critical thinking that ranges from observation and inquiry to argumentation and reflection. Given a broad conception of critical thinking, a developmental approach beginning with children is suggested as a way to help develop critical thinking habits of mind. The conclusion of this analysis is that more emphasis should be placed on developing human intelligence, especially in young children and with the support of artificial intelligence. While much funding and support goes to the development of artificial intelligence, this should not happen at the expense of human intelligence. Overall, the purpose of this paper is to argue for more attention to the development of human intelligence with an emphasis on critical thinking.
Peroxynitrite decomposition catalyst reduces vasopressin requirement in ovine MRSA sepsis
Authors: Fujiwara Osamu , Fukuda Satoshi , Lopez Ernesto , Zeng Yaping , Niimi Yosuke , DeWitt Douglas S. , Herndon David N. , Prough Donald S. , Enkhbaatar Perenlei
Published: September 2019

Background

Sepsis is one of the most frequent causes of death in the intensive care unit. Host vascular hypo-responsiveness to vasopressors during septic shock is one of the challenging problems. This study tested the hypothesis that adjunct therapy with peroxynitrite decomposition catalyst (WW-85) would reduce arginine vasopressin (AVP) requirements during sepsis resuscitation, using ovine sepsis model.

Methods

Thirteen adult female Merino sheep, previously instrumented with multiple vascular catheters, were subjected to “two-hit” (cotton smoke inhalation and intrapulmonary instillation of live methicillin-resistantStaphylococcus aureus; 3.5 × 1011colony-forming units) injury. Post injury, animals were awakened and randomly allocated to the following groups: (1) AVP: injured, fluid resuscitated, and titrated with AVP,n = 6 or (2) WW-85 + AVP: injured, fluid resuscitated, treated with WW-85, and titrated with AVP,n = 7. One-hour post injury, a bolus intravenous injection of WW-85 (0.1 mg/kg) was followed by a 23-h continuous infusion (0.02 mg/kg/h). Titration of AVP started at a dose of 0.01 unit/min, when mean arterial pressure (MAP) decreased by 10 mmHg from baseline, despite aggressive fluid resuscitation, and the rate was further adjusted to maintain MAP. After the injury, all animals were placed on a mechanical ventilator and monitored in the conscious state for 24 h.

Results

The injury induced severe hypotension refractory to aggressive fluid resuscitation. High doses of AVP were required to partially attenuate the sepsis-induced hypotension. However, the cumulative AVP requirement was significantly reduced by adjunct treatment with WW-85 at 17–24 h after the injury (p < 0.05). Total AVP dose and the highest AVP rate were significantly lower in the WW-85 + AVP group compared to the AVP group (p = 0.02 and 0.04, respectively). Treatment with WW-85 had no adverse effects. In addition, the in vitro effects of AVP on isolated artery diameter changes were abolished with peroxynitrite co-incubation.

Conclusions

The modulation of reactive nitrogen species, such as peroxynitrite, may be considered as a novel adjunct treatment option for septic shock associated with vascular hypo-responsiveness to vasopressors.
The effect of 10,12-pentacosadiynoic acid on the morphology and characteristics of electrospun PDA/PU nanofibers
Authors: Kim Myoung Ok , Lee Jung Soon
Published: September 2019

In this study, the effect of 10,12-pentacosadiynoic acid (PCDA) on the fabrication of PDA/PU nanofibers was examined. The PDA/PU nanofibers were prepared by electrospinning PU and PCDA at different mixing ratios, followed by photopolymerization. The viscosity and conductivity of the spinning solution and the morphology of the fabricated nanofibers were analyzed. We also examined the chemical structure changes, physical structure changes, and color transition characteristics of PDA/PU nanofibers. The concentrations of the spinning solutions and the mixing ratio of PCDA and PU had significant effects on the viscosity of the spinning solution and the diameter and shape of the nanofibers. The optimum conditions for economic efficiency and the practicality of the fabrication of a PDA/PU nano-fibers were 12–14 wt% spinning solution and a ratio of PU to PCDA of 4 to 1 or greater. For these conditions, the viscosity was in the range of 225–290 cP, which resulted in the production of smooth, uniform PDA/PU nanofibers without beads. The diameters of the nanofibers ranged from 270 to 550 nm. The results of FT-IR, XRD and DSC analyses confirmed that the PCDA were well mixed with the PU molecules and were electrospun. The fabricated PDA/PU nanofibers exhibited color transition phenomenon by external temperature stimulation above 70 °C.
Comparison of time and cost between conventional surgical planning and virtual surgical planning in orthognathic surgery in Korea
Authors: Park Si-Yeon , Hwang Dae-Seok , Song Jae-Min , Kim Uk-Kyu
Published: September 2019

Background

The purpose of this study was to measure the time of the conventional surgical planning (CSP) and virtual surgical planning (VSP) in orthognathic surgery and to compare them in terms of cost.

Material and method

This is a retrospective study of the patients who underwent orthognathic surgery at the Pusan National University Dental Hospital from December 2017 to August 2018. All the patients were analyzed through both CSP and VSP, and all the surgical stents were fabricated through manual and three-dimensional (3D) printing. The predictor variables were the planning method (CSP vs. VSP) and the surgery type (group I: Le Fort I osteotomy + bilateral sagittal split osteotomy [LFI+BSSO] or group II: only bilateral sagittal split osteotomy [BSSO]), and the outcomes were the time and cost. The results were analyzed using the paired t test.

Results

Thirty patients (12 females, 18 males) met the inclusion criteria, and 17 patients were excluded from the study due to missing or incomplete data. There were 20 group I patients (LFI+BSSO regardless of genioplasty) and 10 group II patients (BSSO regardless of genioplasty). The average time of CSP for group I was 385 ± 7.8 min, and that for group II was 195 ± 8.33 min. The time reduction rate of VSP compared with CSP was 62.8% in group I and 41.5% in group II. On the other hand, there was no statistically significant cost reduction.

Conclusions

The time investment in VSP in this study was significantly smaller than that in CSP, and the difference was greater in group I than in group II.
Mesenchymal stem cell therapies for liver cirrhosis: MSCs as “conducting cells” for improvement of liver fibrosis and regeneration
Authors: Tsuchiya Atsunori , Takeuchi Suguru , Watanabe Takayuki , Yoshida Tomoaki , Nojiri Shunsuke , Ogawa Masahiro , Terai Shuji
Published: September 2019

Mesenchymal stem cells (MSCs) can be cultured relatively easily and can be obtained not only from the bone marrow, but also from medical waste such as adipose tissue and umbilical cord tissue. Because of its low antigenicity, allogeneic MSC injection is safe. MSCs have been evaluated in more than 900 clinical trials in a variety of fields, with more than 50 clinical trials related to liver diseases. Experiments have suggested that MSCs function as “conducting cells” to affect various “effective cells” such as T cells, B cells, and macrophages. Recent clinical trials have focused on allogeneic MSCs. Thus, studies are needed to determine the most effective cell source, culture conditions, cell numbers, administration frequency, administration route, cost, safety, and liver disease treatments. Recently, the functions of exosomes have gained attention, and cell-free therapy may become possible as an alternative therapy for liver disease. In this review, we introduce general information, mechanism, representative clinical study data, recently started or planned clinical trials, and possibility of cell-free therapy of MSCs.
The roles of small RNAs: insights from bacterial quorum sensing
Authors: Fu Hongchang , Elena Rosalía Cardós , Marquez Paola Handal
Published: September 2019

Ribonucleic acids (RNAs) mainly played auxiliary roles in regulations of genetic processes while recent explorations into small non-coding RNAs (sRNAs) in bacteria have broadened the scope of RNAs studies in these processes. sRNAs have been demonstrated to be involved in various genetic processes and to regulate a variety of bacterial physiologies. Comparatively, quorum sensing (QS) is a mature bacterial cell signaling system which regulates bacteria physiologies as well. Prokaryotic sRNAs studies in the status quo have revealed an emerging picture of trans-kingdom signaling regulation and increasing investigations have demonstrated the feasibility of inter-kingdom signaling as the consequence of QS. We therefore review such phenomena and their similarities to investigate the potential of prokaryote-sourced interkingdom signaling and regulation.
Fentanyl versus midazolam as additive to local anesthetic mixture for peribulbar block during posterior segment surgery in adult patients a prospective randomized double-blind study
Authors: Abdalla Mohamed Ahmed , Safan Tamer Fayez
Published: September 2019

Objectives

To evaluate analgesic and hemodynamic outcome of fentanyl or midazolam as additives to local anesthetic mixture (LAM) for peribulbar block (PBB) during posterior chamber surgery.

Methods

One hundred thirty-two ASA status I to III adult patients aged 50–75 years scheduled for posterior segment surgery (intraocular foreign body and elective vitrectomy) were enrolled in this prospective, randomized, double-blind trial from which 12 patients were excluded. After signing a written fully informed consent for study participation, patients were grouped into 3 groups (40 patients in each group); group C received local anesthetic mixture plus 1 ml plain saline, group F received local anesthetic mixture plus 25 μg fentanyl in 1 ml saline and group M received local anesthetic mixture plus 1 mg midazolam in 1 ml saline. The primary outcome was the onset time of eyelid and globe akinesia. Also, the duration of the block was assessed in the three studied groups. Intraoperative and postoperative hemodynamic measures were assessed. Postoperative analgesia was hourly-assessed using Visual analogue scale (VAS) and rescue analgesia was provided at visual analogue score of > 3.

Results

The number of patients who had fast eyelid and globe akinesia was significantly higher with significantly lower total 15-min score in group F than the other groups. Intraoperative and postoperative hemodynamic measures were non-significantly different between studied groups. Duration of the block was significantly longer in groups F and M than group C with significantly longer duration in group F. The number of patients who required postoperative rescue analgesia was significantly lower with significantly lower number of requests in group F than the other groups.

Conclusion

Additives to local anesthetic mixture during peribulbar block provided satisfactory anesthetic outcome than local anesthetic mixture alone. Fentanyl was superior to midazolam in terms of significantly speed up onset, longer block duration with significantly longer postoperative analgesia and lesser consumption of rescue analgesia. Both additives provided adjusted hemodynamic measures comparable to the control group.

Trial registration

Pan African Clinical Trials Registry (PACTR201708002496243) registered 03/08/2017 retrospectively.
Effect of novel phenothiazine derivatives on brain dopamine in Wistar rats
Authors: Gopi Chandravadivelu , Sastry Vedula Girija , Dhanaraju Magharla Dasaratha
Published: September 2019

Background

Neurotransmitters are involved in several functions in the brain and the body of living things. Changes in the level of neurotransmitters in the brain are associated with several illnesses. Some of the drugs are controlling the neurotransmitter by adjusting the level in the brain and are exclusively used in the treatment of psychological disorders. The purpose of the study was to find out the effect of novel synthesised phenothiazine derivatives (GC1, GC2 and GC8) either alone (7.5 mg/kg or 15 mg/kg, oral) or in combination with amphetamine on the experimental animals.

Results

Dopamine level in rat brain was estimated by a spectroscopic method using the UV-visible double beam spectrophotometer at 735 nm. The results revealed that these derivatives blocked the brain dopamine level significantly. The compound GC8 (15 mg/kg) significantly reduced the level of dopamine (0.151 ± 0.04, 0.284 ± 0.03) as similar to that of a standard drug. Furthermore, compounds GC2 (15 mg/kg) and GC1 (15 mg/kg) exhibited a varying level of dopamine inhibition level and have been found at 0.203 ± 0.06 μg/ml, 0.302 ± 0.04 μg/ml, 0.234 ± 0.02 μg/ml and 0.318 ± 0.07 μg/ml, respectively, after the administration of these derivatives either alone or in combination with amphetamine.

Conclusions

The study revealed that the compound 2-amino-6-(3-hydroxy-4-methyl phenyl) pyrimidine-4-yl) (7-chloro-10-(3- (N, N-dimethylamino) propyl)-10H-phenothiazine-3-yl) methanone (GC8, 15 mg/kg) extensively reduced the dopamine level. The order of dopamine-inhibiting effect of the selected compound was found to be GC8 > GC2 > GC1. The increased body weight and relative brain-body weight were also observed in the tested animals due to more intake of food and fluid retention.

Graphical abstract
Synthesis, characterization, and in vitro antimicrobial investigation of novel pyran derivatives based on 8-hydroxyquinoline
Authors: Rbaa Mohamed , Hichar Abdelhadi , Bazdi Omar , Lakhrissi Younes , Ounine Khadija , Lakhrissi Brahim
Published: September 2019

Background

8-Hydroxyquinoline derivatives are known for their extensive applications in the field of analytical chemistry and separation techniques; their complexes with transition metals also exhibit antibacterial and antifungal activity.

Results

In the present study, we synthesized a new series of pyranoquinoline derivatives and evaluated their antibacterial activities. The structures of the synthesized compounds were characterized by Fourier transform infrared (FT-IR), hydrogen-1 nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and elemental analysis. All the prepared compounds were evaluated in vitro as antimicrobial agents against Gram-positive and Gram-negative bacterial strains (Escherichia coli (ATCC35218), Staphylococcus aureus (ATCC29213), Vibrio parahaemolyticus (ATCC17802), and Pseudomonas aeruginosa (ATCC27853)). The screening test was determined by using the standard protocol of disc diffusion method (DDM).

Conclusion

We have synthesized new pyranic compounds bearing an 8-hydroxyquinoline moiety on their structure. The preliminary screening results showed that all the tested compounds have a remarkable inhibitory effect on the growth of the majority of the tested bacterial strains compared to the standard antibiotic (penicillin G), and the chlorinated compound (Q1) is more active against Gram-positive bacteria than Gram-negative bacteria such as the Staphylococcus aureus strain which is the most sensitive. Gram-positive bacteria are responsible for a wide range of infectious diseases, and rising resistance in this group is causing increasing concern. Thus, this study develops novel heterocyclic compound derivatives of 8-hydroxyquinoline that have demonstrated good antibacterial activity against Gram-positive bacteria.

Graphical abstract
CT-2A neurospheres-derived high-grade glioma in mice: a new model to address tumor stem cells and immunosuppression
Authors: Riva Matteo , Wouters Roxanne , Weerasekera Akila , Belderbos Sarah , Nittner David , Thal Dietmar R. , Baert Thaïs , Giovannoni Roberto , Gsell Willy , Himmelreich Uwe , Van Ranst Marc , Coosemans An
Published: September 2019

Background

Recently, several promising treatments for high-grade gliomas (HGGs) failed to provide significant benefit when translated from the preclinical setting to patients. Improving the animal models is fundamental to overcome this translational gap. To address this need, we developed and comprehensively characterized a new in-vivo model based on the orthotopic implantation of CT-2A cells cultured in neurospheres (NS/CT-2A).

Methods

Murine CT-2A methylcholanthrene-induced HGG cells (C57BL/6 background) were cultured in monolayers (ML) or NS and orthotopically inoculated in syngeneic animals. ML/CT-2A and NS/CT-2A tumors’ characterization included the analysis of tumor growth, immune microenvironment, glioma stem cells (GSCs), vascularization and metabolites. The immuno-modulating properties of NS/CT-2A and ML/CT-2A cells on splenocytes were tested in-vitro.

Results

Mice harboring NS/CT-2A tumors survived shorter than those harboring ML/CT-2A tumors (p=0.0033). Compared to standard ML/CT-2A tumors, NS/CT-2A tumors showed more abundant GSCs (p=0.0002 and 0.0770 for Nestin and CD133, respectively) and regulatory T cells (Tregs, p=0.0074), and a strong tendency towards an increased vascularization (p=0.0503). There were no significant differences in metabolites’ composition between NS/ and ML/CT-2A tumors. In-vitro, NS were able to drive splenocytes towards a more immunosuppressive status by reducing CD8+ T cells (p=0.0354) and by promoting Tregs (p=0.0082), macrophages (MF, p=0.0019) and their M2 subset (p=0.0536).

Conclusions

Compared to standard ML/CT-2A tumors, NS/CT-2A tumors show a more aggressive phenotype with increased immunosuppression and GSCs proliferation. Because of these specific features, the NS/CT-2A model represents a clinically relevant platform for the search of new HGG treatments aimed at reducing immunosuppression and eliminating GSCs.
Model systems for regeneration: planarians
Authors: Ivankovic Mario , Haneckova Radmila , Thommen Albert , Grohme Markus A. , Vila-Farré Miquel , Werner Steffen , Rink Jochen C.
Published: September 2019

Planarians are a group of flatworms. Some planarian species have remarkable regenerative abilities, which involve abundant pluripotent adult stem cells. This makes these worms a powerful model system for understanding the molecular and evolutionary underpinnings of regeneration. By providing a succinct overview of planarian taxonomy, anatomy, available tools and the molecular orchestration of regeneration, this Primer aims to showcase both the unique assets and the questions that can be addressed with this model system.
Developmentally regulated Shh expression is robust to TAD perturbations
Authors: Williamson Iain , Kane Lauren , Devenney Paul S. , Flyamer Ilya M. , Anderson Eve , Kilanowski Fiona , Hill Robert E. , Bickmore Wendy A. , Lettice Laura A.
Published: September 2019

Topologically associating domains (TADs) have been proposed to both guide and constrain enhancer activity. Shh is located within a TAD known to contain all its enhancers. To investigate the importance of chromatin conformation and TAD integrity on developmental gene regulation, we have manipulated the Shh TAD – creating internal deletions, deleting CTCF sites, and deleting and inverting sequences at TAD boundaries. Chromosome conformation capture and fluorescence in situ hybridisation assays were used to investigate the changes in chromatin conformation that result from these manipulations. Our data suggest that these substantial alterations in TAD structure have no readily detectable effect on Shh expression patterns or levels of Shh expression during development – except where enhancers are deleted – and result in no detectable phenotypes. Only in the case of a larger deletion at one TAD boundary could ectopic influence of the Shh limb enhancer be detected on a gene (Mnx1) in the neighbouring TAD. Our data suggests that, contrary to expectations, the developmental regulation of Shh expression is remarkably robust to TAD perturbations.
Selection for reproduction under short photoperiods changes diapause-associated traits and induces widespread genomic divergence
Authors: Kauranen Hannele , Kinnunen Johanna , Hiillos Anna-Lotta , Lankinen Pekka , Hopkins David , Wiberg R. Axel W. , Ritchie Michael G. , Hoikkala Anneli
Published: September 2019

The incidence of reproductive diapause is a critical aspect of life history in overwintering insects from temperate regions. Much has been learned about the timing, physiology and genetics of diapause in a range of insects, but how the multiple changes involved in this and other photoperiodically regulated traits are interrelated is not well understood. We performed quasinatural selection on reproduction under short photoperiods in a northern fly species, Drosophila montana, to trace the effects of photoperiodic selection on traits regulated by the photoperiodic timer and / or by a circadian clock system. Selection changed several traits associated with reproductive diapause, including the critical day length for diapause (CDL), the frequency of diapausing females under photoperiods that deviate from daily 24 h cycles and cold tolerance, towards the phenotypes typical of lower latitudes. However, selection had no effect on the period of free-running locomotor activity rhythm regulated by the circadian clock in fly brain. At a genomic level, selection induced extensive divergence between the selection and control line replicates in 16 gene clusters involved in signal transduction, membrane properties, immunologlobulins and development. These changes resembled ones detected between latitudinally divergent D. montana populations in the wild and involved SNP divergence associated with several genes linked with diapause induction. Overall, our study shows that photoperiodic selection for reproduction under short photoperiods affects diapause-associated traits without disrupting the central clock network generating circadian rhythms in fly locomor activity.
Drivers of the dive response in trained harbour porpoises(Phocoena phocoena)
Authors: Elmegaard S. L. , McDonald B. I. , Madsen P. T.
Published: September 2019

Pronounced dive responses through peripheral vasoconstriction and bradycardia enables prolonged apnoea in marine mammals. For most vertebrates, the dive response is initiated upon face immersion, but little is known about the physical drivers of diving and surfacing heart rate in cetaceans whose faces are always mostly submerged. Using two trained harbour porpoises instrumented with an ECG-measuring DTAG-3, we investigate the initiation and progression of bradycardia and tachycardia during apnoea and eupnoea for varying levels of immersion. We show that paranasal wetting drives bradycardia initiation and progression, whereas apnoea leads to dive-level bradycardia eventually, but not instantly. At the end of dives, heart rate accelerates independently of lung expansion, perhaps in anticipation of surfacing; however, full tachycardia is only engaged upon inhalation. We conclude that breathing drives surface tachycardia, whereas blowhole wetting is an important driver of bradycardia; although, anticipatory/volitional modulation can overrule such responses to sensory inputs.
Acute effects of intense exercise on the antioxidant system in birds: does exercise training help?
Authors: Cooper-Mullin Clara , Carter Wales , McWilliams Scott
Published: September 2019

The acute effects of an energy-intensive activity such as exercise may alter an animal's redox homeostasis, although these short-term effects may be ameliorated by chronic exposure to that activity, or training, over time. Although well documented in mammals, how energy-intensive training affects the antioxidant system and damage by reactive species has not been investigated fully in flight-trained birds. We examined changes to redox homeostasis in Zebra Finches exposed to energy-intensive activity (60 min of perch-to-perch flights twice a day), and how exercise training over many weeks affected this response. We measured multiple components of the antioxidant system: an enzymatic antioxidant (glutathione peroxidase, GPx) and non-enzymatic antioxidants (measured by the OXY-adsorbent test) as well as a measure of oxidative damage (d-ROMs). At no point during the experiment did oxidative damage change. We discovered that exposure to energy-intensive exercise training did not alter baseline levels of GPx, but induced exercise-trained birds to maintain a higher non-enzymatic antioxidant status as compared with untrained birds. GPx activity was elevated above baseline in trained birds immediately after completion of the second one-hour flight on each of the three sampling days, and non-enzymatic antioxidants were acutely depleted during flight after 13 and 44 days of training. The primary effect of exercise training on the acute response of the antioxidant system to 2-hr flights was increased coordination between the enzymatic (GPx) and non-enzymatic components of the antioxidant system of birds that reduced oxidative damage associated with exercise.