bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving case detection of tuberculosis in hospitalised Kenyan children—employing the behaviour change wheel to aid intervention design and implementation
Authors: Oliwa Jacquie Narotso , Nzinga Jacinta , Masini Enos , van Hensbroek Michaël Boele , Jones Caroline , English Mike , van’t Hoog Anja
Published: November 2020

Background

The true burden of tuberculosis in children remains unknown, but approximately 65% go undetected each year. Guidelines for tuberculosis clinical decision-making are in place in Kenya, and the National Tuberculosis programme conducts several trainings on them yearly. By 2018, there were 183 GeneXpert® machines in Kenyan public hospitals. Despite these efforts, diagnostic tests are underused and there is observed under detection of tuberculosis in children. We describe the process of designing a contextually appropriate, theory-informed intervention to improve case detection of TB in children and implementation guided by the Behaviour Change Wheel.

Methods

We used an iterative process, going back and forth from quantitative and qualitative empiric data to reviewing literature, and applying the Behaviour Change Wheel guide. The key questions reflected on included (i) what is the problem we are trying to solve; (ii) what behaviours are we trying to change and in what way; (iii) what will it take to bring about desired change; (iv) what types of interventions are likely to bring about desired change; (v) what should be the specific intervention content and how should this be implemented?

Results

The following behaviour change intervention functions were identified as follows: (i) training: imparting practical skills; (ii) modelling: providing an example for people to aspire/imitate; (iii) persuasion: using communication to induce positive or negative feelings or stimulate action; (iv) environmental restructuring: changing the physical or social context; and (v) education: increasing knowledge or understanding. The process resulted in a multi-faceted intervention package composed of redesigning of child tuberculosis training; careful selection of champions; use of audit and feedback linked to group problem solving; and workflow restructuring with role specification.

Conclusion

The intervention components were selected for their effectiveness (from literature), affordability, acceptability, and practicability and designed so that TB programme officers and hospital managers can be supported to implement them with relative ease, alongside their daily duties. This work contributes to the field of implementation science by utilising clear definitions and descriptions of underlying mechanisms of interventions that will guide others to do likewise in their settings for similar problems.
Integrating sexual and reproductive health into health system strengthening in humanitarian settings: a planning workshop toolkit to transition from minimum to comprehensive services in the Democratic Republic of Congo, Bangladesh, and Yemen
Authors: Tran Nguyen Toan , Greer Alison , Kini Brigitte , Abdi Hassan , Rajeh Kariman , Cortier Hilde , Boboeva Mohira
Published: November 2020

Background

Planning to transition from the Minimum Initial Service Package for Sexual and Reproductive Health (SRH) toward comprehensive SRH services has been a challenge in humanitarian settings. To bridge this gap, a workshop toolkit for SRH coordinators was designed to support effective planning. This article aims to describe the toolkit design, piloting, and final product.

Methods

Anchored in the Health System Building Blocks Framework of the World Health Organization, the design entailed two complementary and participatory strategies. First, a collaborative design phase with iterative feedback loops involved global partners with extensive operational experience in the initial toolkit conception. The second phase engaged stakeholders from three major humanitarian crises to participate in pilot workshops to contextualize, evaluate, validate, and improve the toolkit using qualitative interviews and end-of-workshop evaluations. The aim of this two-phase design process was to finalize a planning toolkit that can be utilized in and adapted to diverse humanitarian contexts, and efficiently and effectively meet its objectives. Pilots occurred in the Democratic Republic of Congo for the Kasai region crisis, Bangladesh for the Rohingya humanitarian response in Cox’s Bazar, and Yemen for selected Governorates.

Results

Results suggest that the toolkit enabled facilitators to foster a systematic, participatory, interactive, and inclusive planning process among participants over a two-day workshop. The approach was reportedly effective and time-efficient in producing a joint work plan. The main planning priorities cutting across settings included improving comprehensive SRH services in general, healthcare workforce strengthening, such as midwifery capacity development, increasing community mobilization and engagement, focusing on adolescent SRH, and enhancing maternal and newborn health services in terms of quality, coverage, and referral pathways. Recommendations for improvement included a dedicated and adequately anticipated pre-workshop preparation to gather relevant data, encouraging participants to undertake preliminary study to equalize knowledge to partake fully in the workshop, and enlisting participants from marginalized and underserved populations.

Conclusion

Collaborative design and piloting efforts resulted in a workshop toolkit that could support a systematic and efficient identification of priority activities and services related to comprehensive SRH. Such priorities could help meet the SRH needs of communities emerging from acute humanitarian situations while strengthening the overall health system.
Targeting autophagy to overcome drug resistance: further developments
Authors: Chang Haocai , Zou Zhengzhi
Published: November 2020

Inhibiting cell survival and inducing cell death are the main approaches of tumor therapy. Autophagy plays an important role on intracellular metabolic homeostasis by eliminating dysfunctional or unnecessary proteins and damaged or aged cellular organelles to recycle their constituent metabolites that enable the maintenance of cell survival and genetic stability and even promotes the drug resistance, which severely limits the efficacy of chemotherapeutic drugs. Currently, targeting autophagy has a seemingly contradictory effect to suppress and promote tumor survival, which makes the effect of targeting autophagy on drug resistance more confusing and fuzzier. In the review, we summarize the regulation of autophagy by emerging ways, the action of targeting autophagy on drug resistance and some of the new therapeutic approaches to treat tumor drug resistance by interfering with autophagy-related pathways. The full-scale understanding of the tumor-associated signaling pathways and physiological functions of autophagy will hopefully open new possibilities for the treatment of tumor drug resistance and the improvement in clinical outcomes.
Chemoprotective effects of plasma derived from mice of different ages and genders on ovarian failure after cyclophosphamide treatment
Authors: Bahmanpour Soghra , Moradiyan Eisa , Dehghani Farzaneh , Zarei-fard Nehleh
Published: November 2020

Background

Premature ovarian failure is one of the major side effects of chemotherapy drugs. Blood plasma contains several factors that might lead to the repair of different tissues.

Objective

The chemoprotective effects of plasma derived from mice with different ages and genders were assessed on ovarian tissue in cyclophosphamide-treated mice.

Methods

Forty-two adult female mice were divided into six groups as follows: (A) control; (B) 0.9% sodium chloride as vehicle; (C) cyclophosphamide; (D) cyclophosphamide + young male blood plasma; (E) cyclophosphamide + old male blood plasma; (F) cyclophosphamide + young female blood plasma. Ovarian failure was induced by injecting cyclophosphamide. On the 1st day, three groups received simultaneous injections of 150 μL intraperitoneal and 70 μL intravenous plasma derived from mice of different ages and genders. Each plasma type (150 μL) was then injected intraperitoneally every other 3 days for 19 days. On day 21, the dissected ovaries were stained for stereological analysis. Also, estrogen and progesterone levels were measured.

Results

Cyclophosphamide had damaging effects on ovarian parameters and led to reduced hormone levels in comparison with the control group. However, treating with young female and, old male blood plasma, to a lesser degree, showed beneficial effects on the number of primordial follicles, pre-antral follicles, and granulosa cells. Also, these two treatments had protective effects on the volume of ovarian parameters as well as estrogen and progesterone levels in comparison with the cyclophosphamide group (P < 0.05).

Conclusion

Plasma derived from mice of different ages and genders can ameliorate premature ovarian failure against the adverse effects of cyclophosphamide.
Individualized flow-controlled ventilation compared to best clinical practice pressure-controlled ventilation: a prospective randomized porcine study
Authors: Spraider Patrick , Martini Judith , Abram Julia , Putzer Gabriel , Glodny Bernhard , Hell Tobias , Barnes Tom , Enk Dietmar
Published: November 2020

Background

Flow-controlled ventilation is a novel ventilation method which allows to individualize ventilation according to dynamic lung mechanic limits based on direct tracheal pressure measurement at a stable constant gas flow during inspiration and expiration. The aim of this porcine study was to compare individualized flow-controlled ventilation (FCV) and current guideline-conform pressure-controlled ventilation (PCV) in long-term ventilation.

Methods

Anesthetized pigs were ventilated with either FCV or PCV over a period of 10 h with a fixed FiO2of 0.3. FCV settings were individualized by compliance-guided positive end-expiratory pressure (PEEP) and peak pressure (Ppeak) titration. Flow was adjusted to maintain normocapnia and the inspiration to expiration ratio (I:E ratio) was set at 1:1. PCV was performed with a PEEP of 5 cm H2O andPpeakwas set to achieve a tidal volume (VT) of 7 ml/kg. The respiratory rate was adjusted to maintain normocapnia and the I:E ratio was set at 1:1.5. Repeated measurements during observation period were assessed by linear mixed-effects model.

Results

In FCV (n = 6), respiratory minute volume was significantly reduced (6.0 vs 12.7, MD − 6.8 (− 8.2 to − 5.4) l/min;p < 0.001) as compared to PCV (n = 6). Oxygenation was improved in the FCV group (paO2119.8 vs 96.6, MD 23.2 (9.0 to 37.5) Torr; 15.97 vs 12.87, MD 3.10 (1.19 to 5.00) kPa;p = 0.010) and CO2removal was more efficient (paCO240.1 vs 44.9, MD − 4.7 (− 7.4 to − 2.0) Torr; 5.35 vs 5.98, MD − 0.63 (− 0.99 to − 0.27) kPa;p = 0.006).Ppeakand driving pressure were comparable in both groups, whereas PEEP was significantly lower in FCV (p = 0.002). Computed tomography revealed a significant reduction in non-aerated lung tissue in individualized FCV (p = 0.026) and no significant difference in overdistended lung tissue, although a significantly higherVTwas applied (8.2 vs 7.6, MD 0.7 (0.2 to 1.2) ml/kg;p = 0.025).

Conclusion

Our long-term ventilation study demonstrates the applicability of a compliance-guided individualization of FCV settings, which resulted in significantly improved gas exchange and lung tissue aeration without signs of overinflation as compared to best clinical practice PCV.
Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study
Authors: Kühn Dennis , Metz Carlos , Seiler Frederik , Wehrfritz Holger , Roth Sophie , Alqudrah Mohammad , Becker André , Bracht Hendrik , Wagenpfeil Stefan , Hoffmann Mathias , Bals Robert , Hübner Ulrich , Geisel Jürgen , Lepper Philipp M. , Becker Sören L.
Published: November 2020

Background

Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO.

Methods

Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints.

Results

The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem.

Conclusions

ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.
Surveillance of dengue virus in individual Aedes aegypti mosquitoes collected concurrently with suspected human cases in Tarlac City, Philippines
Authors: Balingit Jean Claude , Carvajal Thaddeus M. , Saito-Obata Mariko , Gamboa Maribet , Nicolasora Amalea Dulcene , Sy Ava Kristy , Oshitani Hitoshi , Watanabe Kozo
Published: November 2020

Background

Vector control measures are critical for the prevention and reduction of dengue virus (DENV) transmission. Effective vector control is reliant not only on knowledge of mosquito abundance, but also on the timely and accurate detection of mosquito-borne infection. Mosquito-based virus surveillance programs typically rely on pool-based mosquito testing, although whether individual-based mosquito testing is a feasible alternative to this has not been widely studied. Applying an individual-based mosquito testing approach, we conducted a 1-month surveillance study of DENV in adultAedes aegyptimosquitoes in homes of suspected dengue patients during the 2015 peak dengue season in Tarlac City, Philippines to more accurately assess the mosquito infection rate and identify the DENV serotypes and genotypes concurrently co-circulating in mosquitoes and patients there.

Methods

We performed a one-step multiplex real-time reverse transcription-polymerase chain reaction (RT-PCR) assay for the simultaneous detection and serotyping of DENV in patients and individual femaleAe. aegyptimosquitoes. Additionally, we performed sequencing and phylogenetic analyses to further characterize the detected DENV serotypes in mosquitoes and patients at the genotype level.

Results

We collected a total of 583 adultAe. aegyptimosquitoes, of which we individually tested 359 female mosquitoes for the presence of DENV. Ten (2.8%) of the 359 female mosquitoes were positive for the presence of DENV. We detected DENV-1, DENV-2, and DENV-4 in the field-collected mosquitoes, which was consistent with the serotypes concurrently found in infected patients. Sequencing and phylogenetic analyses of the detected DENV serotypes based on the partial sequence of the evelope (E) gene revealed three genotypes concurrently present in the sampled mosquitoes and patients during the study period, namely DENV-1 genotype IV, DENV-2 Cosmopolitan genotype, and DENV-4 genotype II.

Conclusions

We demonstrated the utility of a one-step multiplex real-time RT-PCR assay for the individual-based DENV surveillance of mosquitoes. Our findings reinforce the importance of detecting and monitoring virus activity in local mosquito populations, which are critical for dengue prevention and control.
Use of Oxford Nanopore MinION to generate full-length sequences of the Blastocystis small subunit (SSU) rRNA gene
Authors: Maloney Jenny G. , Molokin Aleksey , Santin Monica
Published: November 2020

Background

Blastocystis sp. is one of the most common enteric parasites of humans and animals worldwide. It is well recognized that this ubiquitous protist displays a remarkable degree of genetic diversity in the SSU rRNA gene, which is currently the main gene used for defining Blastocystis subtypes. Yet, full-length reference sequences of this gene are available for only 16 subtypes of Blastocystis in part because of the technical difficulties associated with obtaining these sequences from complex samples.

Methods

We have developed a method using Oxford Nanopore MinION long-read sequencing and universal eukaryotic primers to produce full-length (> 1800 bp) SSU rRNA gene sequences for Blastocystis. Seven Blastocystis specimens representing five subtypes (ST1, ST4, ST10, ST11, and ST14) obtained both from cultures and feces were used for validation.

Results

We demonstrate that this method can be used to produce highly accurate full-length sequences from both cultured and fecal DNA isolates. Full-length sequences were successfully obtained from all five subtypes including ST11 for which no full-length reference sequence currently exists and for an isolate that contained mixed ST10/ST14.

Conclusions

The suitability of the use of MinION long-read sequencing technology to successfully generate full-length Blastocystis SSU rRNA gene sequences was demonstrated. The ability to produce full-length SSU rRNA gene sequences is key in understanding the role of genetic diversity in important aspects of Blastocystis biology such as transmission, host specificity, and pathogenicity.

Graphical Abstract
Production and partial characterization of a crude cold-active cellulase (CMCase) from Bacillus mycoides AR20-61 isolated from an Alpine forest site
Authors: Steiner Elisa , Margesin Rosa
Published: November 2020

Purpose

To evaluate the production of a cold-active CMCase (endoglucanase) by Bacillus mycoides AR20-61 isolated from Alpine forest soil and to characterize the crude enzyme.

Methods

After studying the effect of cultivation parameters (medium composition, temperature, NaCl concentration, pH) on bacterial growth and enzyme production, the crude enzyme was characterized with regard to the effect of pH, temperature, and inhibitors on enzyme activity and stability.

Result

Optimum growth and enzyme production occurred at 20–25 °C, pH 7, and 1–1.5% (w/v) CMC. Despite high biomass production over the whole growth temperature range (10–35 °C), enzyme production was low at 10 and 35 °C. CMC concentration had a minor effect on growth, independent of the growth temperature, but a significant effect on CMCase production at temperatures ≥ 20 °C. The crude enzyme was active over a broad temperature range (0–60 °C); the apparent optimum temperature for activity was at 40–50 °C. The cultivation temperature influenced the effect of temperature on enzyme activity and stability. A significantly higher thermosensitivity of the enzyme produced at a cultivation temperature of 10 °C compared to that produced at 25 °C was noted at 50 and 65 °C. The enzyme was highly active over a pH range of 4–6 and showed optimum activity at pH 5. No activity was lost after 60 min of incubation at 30 °C and pH 4–9. The CMCase was resistant against a number of monovalent and divalent metal ions, metal-chelating agents, and phenol.

Conclusion

The CMCase produced by the studied strain is characterized by high activities in the low temperature range (down to 0 °C) and acidic pH range, high stability over a broad pH range, and high resistance against a number of effectors. Our results also demonstrate the different, independent roles of temperature in bacterial growth, enzyme production, nutrient requirements during enzyme production, and enzyme characteristics regarding thermosensitivity, which has not yet been described for cellulases.
Transplantation of photobiomodulation-preconditioned diabetic stem cells accelerates ischemic wound healing in diabetic rats
Authors: Ahmadi Houssein , Amini Abdollah , Fadaei Fathabady Fatemeh , Mostafavinia Atarodsadat , Zare Fatemeh , Ebrahimpour-malekshah Roohollah , Ghalibaf Mustafa Neshat , Abrisham Matin , Rezaei Fatemehalsadat , Albright Richard , Ghoreishi Seyed Kamran , Chien Sufan , Bayat Mohammad
Published: November 2020

Background

Diabetic foot ulcer is the most costly and complex challenge for patients with diabetes. We hereby assessed the effectiveness of different preconditioned adipose-derived mesenchymal stem cells (AD-MSCs) and photobiomodulation protocols on treating an infected ischemic wound in type 1 diabetic rats.

Methods

There were five groups of rats: (1) control, (2) control AD-MSCs [diabetic AD-MSCs were transplanted (grafted) into the wound bed], (3) AD-MSC + photobiomodulation in vivo (diabetic AD-MSCs were grafted into the wound, followed by in vivo PBM treatment), (4) AD-MSCs + photobiomodulation in vitro, and (5) AD-MSCs + photobiomodulation in vitro + in vivo.

Results

Diabetic AD-MSCs preconditioned with photobiomodulation had significantly risen cell function compared to diabetic AD-MSC. Groups 3 and 5 had significantly decreased microbial flora correlated to groups 1 and 2 (all, p = 0.000). Groups 2, 3, 4, and 5 had significantly improved wound closure rate (0.4, 0.4, 0.4, and 0.8, respectively) compared to group 1 (0.2). Groups 2–5 had significantly increased wound strength compared to group 1 (all p = 0.000). In most cases, group 5 had significantly better results than groups 2, 3, and 4.

Conclusions

Preconditioning diabetic AD-MSCs with photobiomodulation in vitro plus photobiomodulation in vivo significantly hastened healing in the diabetic rat model of an ischemic infected delayed healing wound.
Improving cell survival and engraftment in vivo via layer-by-layer nanocoating of hESC-derived RPE cells
Authors: Ru Liyan , Wu Nan , Wei Keyu , Zeng Yuxiao , Li Qiyou , Weng Chuanhuang , Ren Chunge , Ren Bangqi , Huo Da , Li Yijian , Hu Xisu , Qin Zuoxin , Fang Yajie , Zhu Chuhong , Liu Yong
Published: November 2020

Background

Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cell transplants have served as a cell therapy for treating retinal degenerative diseases. However, how to optimize the survival and engraftment of hESC-RPE cells is a great challenge.

Methods

Here, we report hESC-RPE cells that are embedded with polyelectrolytes gelatin and alginate by layer-by-layer (LbL) self-assembly technique, based on the opposite charge of alternate layers. Cells were assessed for cell survival, immunogenicity, and function in vitro and in vivo.

Results

This strategy obviously decreased the immunogenicity of hESC-RPE cells without affecting its activity. LbL-RPE cell transplants into the subretinal space of Royal College of Surgeons (RCS) rats optimized cell engraftment and decreased immunogenicity compared to untreated RPE cell transplants (immunosuppression was not used during the 21-week study). Visual-functional assay with electroretinogram recordings (ERGs) also showed higher B wave amplitudes in RCS rats with LbL-RPE cell transplants.

Conclusions

We demonstrate that transplanted LbL-RPE cells have better viability and grafting efficiency, optimized immunogenicity, and visual function. Therefore, LbL engineering is a promising method to increase the efficacy of hESC-RPE cell transplantation.
Bone marrow mesenchymal stem cell-derived exosomes promote rotator cuff tendon-bone healing by promoting angiogenesis and regulating M1 macrophages in rats
Authors: Huang Yao , He Bing , Wang Lei , Yuan Bin , Shu Hao , Zhang Fucheng , Sun Luning
Published: November 2020

Background

Rotator cuff tears (RCTs) often require reconstructive surgery. Tendon-bone healing is critical for the outcome of rotator cuff reconstruction, but the process of tendon-bone healing is complex and difficult. Mesenchymal stem cells (MSCs) are considered to be an effective method to promote tendon-bone healing. MSCs have strong paracrine, anti-inflammatory, immunoregulatory, and angiogenic potential. Recent studies have shown that MSCs achieve many regulatory functions through exosomes. The purpose of this study was to explore the role of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) in tendon-bone healing.

Methods

Our study found that BMSC-Exos promote the proliferation, migration, and angiogenic tube formation of human umbilical vein endothelial cells (HUVECs). The mechanism by which BMSC-Exos achieve this may be through the regulation of the angiogenic signaling pathway. In addition, BMSC-Exos can inhibit the polarization of M1 macrophages and inhibit the secretion of proinflammatory factors by M1 macrophages. After rotator cuff reconstruction in rats, BMSC-Exos were injected into the tail vein to analyze their effect on the rotator cuff tendon-bone interface healing.

Results

It was confirmed that BMSC-Exos increased the breaking load and stiffness of the rotator cuff after reconstruction in rats, induced angiogenesis around the rotator cuff endpoint, and promoted growth of the tendon-bone interface.

Conclusion

BMSC-Exos promote tendon-bone healing after rotator cuff reconstruction in rats by promoting angiogenesis and inhibiting inflammation.
Extracellular vesicles from hydroxycamptothecin primed umbilical cord stem cells enhance anti-adhesion potential for treatment of tendon injury
Authors: Li Juehong , Yao Zhixiao , Xiong Hao , Cui Haomin , Wang Xu , Zheng Wei , Qian Yun , Fan Cunyi
Published: November 2020

Background

Peritendinous fibrosis represents a fibrotic healing process that usually occurs after tendon injury or surgery. This worldwide challenge hampers the functional rehabilitation and the mobility of extremities. However, effective treatment is still lacking at present. The aim of our study was to explore the effect of extracellular vesicles derived from hydroxycamptothecin primed human umbilical cord stem cells (HCPT-EVs) on post-traumatic tendon adhesion.

Methods

Extracellular vesicles derived from unprimed human umbilical cord mesenchymal stem cells (Unprimed EVs) or HCPT-EVs were isolated and characterized. A rat model of Achilles tendon injury was used to confirm the anti-adhesion effect of HCPT-EVs and compared with that of Unprimed EVs in vivo. In vitro, the inhibitory effects of HCPT-EVs on fibroblast proliferation, viability, and myofibroblast differentiation upon TGF-β1 stimulation were compared with the effects of Unprimed EVs. For mechanistic analysis, the expression of endoplasmic reticulum stress (ERS)-associated proteins was examined among the effector cargos of HCPT-EVs and Unprimed EVs. The ERS antagonist salubrinal was used to determine the ERS dependence of the anti-adhesion effects of HCPT-EVs.

Results

There were no obvious differences between Unprimed EVs and HCPT-EVs in terms of morphology, particle size, characteristic protein expression, and cellular uptake. HCPT-EVs exhibited a fortified anti-adhesion effect after Achilles tendon injury compared with Unprimed EVs. Fibroblast proliferation and viability and myofibroblast differentiation were all inhibited by HCPT-EVs. These properties were superior for HCPT-EVs relative to Unprimed EVs. Mechanistically, HCPT-EVs contained more ERS-associated protein than Unprimed EVs and activated the ERS pathway in fibroblast to counteract myofibroblast differentiation.

Conclusion

This study demonstrates that HCPT-EVs show high anti-adhesion potential for the treatment of tendon injury by provoking ERS in fibroblasts. HCPT-EVs represent a promising strategy for clinical use in treating adhesion-related diseases.
Human levator veli palatini muscle: a novel source of mesenchymal stromal cells for use in the rehabilitation of patients with congenital craniofacial malformations
Authors: Bueno Daniela Franco , Kabayashi Gerson Shigueru , Pinheiro Carla Cristina Gomes , Tanikawa Daniela Y. S. , Raposo-Amaral Cassio Eduardo , Rocha Diogenes Laercio , Ferreira José Ricardo Muniz , Shibuya Yoichiro , Hokugo Akishige , Jarrahy Reza , ZuK Patricia A. , Passos-Bueno Maria Rita
Published: November 2020

Background

Bone reconstruction in congenital craniofacial differences, which affect about 2–3% of newborns, has long been the focus of intensive research in the field of bone tissue engineering. The possibility of using mesenchymal stromal cells in regenerative medicine protocols has opened a new field of investigation aimed at finding optimal sources of multipotent cells that can be isolated via non-invasive procedures. In this study, we analyzed whetherlevator veli palatinimuscle fragments, which can be readily obtained in non-invasive manner during palatoplasty in cleft palate patients, represent a novel source of MSCs with osteogenic potential.

Methods

We obtainedlevator veli palatinimuscle fragments (3–5 mm3), during surgical repair of cleft palate in 5 unrelated patients. Mesenchymal stromal cells were isolated from the muscle using a pre-plating technique and other standard practices. The multipotent nature of the isolated stromal cells was demonstrated via flow cytometry analysis and by induction along osteogenic, adipogenic, and chondrogenic differentiation pathways. To demonstrate the osteogenic potential of these cells in vivo, they were used to reconstruct a critical-sized full-thickness calvarial defect model in immunocompetent rats.

Results

Flow cytometry analysis showed that the isolated stromal cells were positive for mesenchymal stem cell antigens (CD29, CD44, CD73, CD90, and CD105) and negative for hematopoietic (CD34 and CD45) or endothelial cell markers (CD31). The cells successfully underwent osteogenic, chondrogenic, and adipogenic cell differentiation under appropriate cell culture conditions. Calvarial defects treated with CellCeram™ scaffolds seeded with the isolatedlevator veli palatinimuscle cells showed greater bone healing compared to defects treated with acellular scaffolds.

Conclusion

Cells derived fromlevator veli palatinimuscle have phenotypic characteristics similar to other mesenchymal stromal cells, both in vitro and in vivo. Our findings suggest that these cells may have clinical relevance in the surgical rehabilitation of patients with cleft palate and other craniofacial anomalies characterized by significant bone deficit.
Exosomes derived from three-dimensional cultured human umbilical cord mesenchymal stem cells ameliorate pulmonary fibrosis in a mouse silicosis model
Authors: Xu Chunjie , Zhao Jing , Li Qiuyue , Hou Lin , Wang Yan , Li Siling , Jiang Fuyang , Zhu Zhonghui , Tian Lin
Published: November 2020

Background

Silicosis is an occupational respiratory disease caused by long-term excessive silica inhalation, which is most commonly encountered in industrial settings. Unfortunately, there is no effective therapy to delay and cure the progress of silicosis. In the recent years, stem cell therapy has emerged as an attractive tool against pulmonary fibrosis (PF) owing to its unique biological characteristics. However, the direct use of stem cells remains limitation by many risk factors for therapeutic purposes. The exclusive utility of exosomes secreted from stem cells, rather than cells, has been considered a promising alternative to overcome the limitations of cell-based therapy while maintaining its advantages.

Methods and results

In this study, we first employed a three-dimensional (3D) dynamic system to culture human umbilical cord mesenchymal stem cell (hucMSC) spheroids in a microcarrier suspension to yield exosomes from serum-free media. Experimental silicosis was induced in C57BL/6J mice by intratracheal instillation of a silica suspension, with/without exosomes derived from hucMSC (hucMSC-Exos), injection via the tail vein afterwards. The results showed that the gene expression of collagen I (COL1A1) and fibronectin (FN) was upregulated in the silica group as compared to that in the control group; however, this change decreased with hucMSC-Exo treatment. The value of FEV0.1 decreased in the silica group as compared to that in the control group, and this change diminished with hucMSC-Exo treatment. These findings suggested that hucMSC-Exos could inhibit silica-induced PF and regulate pulmonary function. We also performed in vitro experiments to confirm these findings; the results revealed that hucMSC-Exos decreased collagen deposition in NIH-3T3 cells exposed to silica.

Conclusions

Taken together, these studies support a potential role for hucMSC-Exos in ameliorating pulmonary fibrosis and provide new evidence for improving clinical treatment induced by silica.
Pharmacokinetic modeling of Gadolinium nanoparticles (Gd-NPs) with the sojourn time in vasa vasorum for the contrast enhanced MRI
Authors: Prommarat Angkhana , Chamchod Farida
Published: November 2020

Deposition of lipid in the artery wall called atherosclerosis is recognized as a major cause of cardiovascular disease that leads to death worldwide. A better understanding into factors that may influence the delivery of gadolinium nanoparticles (Gd-NPs) that enhances quality of magnetic resonance imaging in diagnosis may provide a vital key for atherosclerotic treatment. In this study, we propose a delay differential model for describing the dynamics of Gd-NPs in bloodstream, peripheral arteries, and vasa vasorum with two phenomena of Gd-NPs during a sojourn in vasa vasorum. We then investigate the dynamical behaviors of Gd-NPs and explore the effects of sojourn time and transfer rates of Gd-NPs on the concentration of Gd-NPs in vasa vasorum at the 12th hour after the administration of gadolinium chelates contrast media and also the maximum concentration of Gd-NPs in peripheral arteries and vasa vasorum. Our results suggest that the sojourn of Gd-NPs in vasa vasorum may lead to complex behaviors of Gd-NPs dynamics, and transfer rates of Gd-NPs may have a significant impact on the concentration of Gd-NPs.
Celastrol-mediated autophagy regulation in cancer
Authors: Haroon Muhammad , Kang Sun Chul
Published: November 2020

In the last few decades, studies on autophagy regulation and its potential role in cancer therapeutics have expanded to include detailed mechanisms. Since apoptosis exhibits drug resistance in some cancers, efforts have focused on searching for compounds with autophagy modulating properties. Numerous natural compounds have been used in cancer treatment and are considered a significant research area due to their remarkable anti-cancer properties. Celastrol, a quinone methide triterpene, derived from Tripterygium wilfordii, has recently drawn much attention because of its anticancer potential. It enhances tumor suppression and induces autophagy in cancer cells by regulating signaling pathways such as Beclin-1, Akt/mTOR, ROS, NF-κB, MAPK, HSP90, and the proteasome. In the current study, we address the anticancer potential of celastrol, its effect on various cellular pathways, and describe how it functions as an autophagy modulator in cancer therapeutics and helps diminish multidrug resistance in cancer cells.
Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19
Authors: Yang Peng-Hui , Ding Yi-Bo , Xu Zhe , Pu Rui , Li Ping , Yan Jin , Liu Ji-Luo , Meng Fan-Ping , Huang Lei , Shi Lei , Jiang Tian-Jun , Qin En-Qiang , Zhao Min , Zhang Da-Wei , Zhao Peng , Yu Ling-Xiang , Wang Zhao-Hai , Hong Zhi-Xian , Xiao Zhao-Hui , Xi Qing , Zhao De-Xi , Yu Peng , Zhu Cai-Zhong , Chen Zhu , Zhang Shao-Geng , Ji Jun-Sheng , Wang Fu-Sheng , Cao Guang-Wen
Published: November 2020

Background

Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression.

Methods

Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ2 test or the Fisher exact test (categorical variables) and independent group t test or Mann–Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19.

Results

The mean incubation was 8.67 (95% confidence interval, 6.78–10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86–12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (< 190/µl) of CD8+ T cells, and neutrophil/lymphocyte ratio. Thirteen patients deteriorated during hospitalization. Cox regression analysis indicated that older age and higher serum levels of interleukin-6, C-reactive protein, procalcitonin, and lactate at admission significantly predicted the progression of COVID-19. During hospitalization, circulating counts of T lymphocytes, CD4+ T cells, and CD8+ T cells were lower, whereas neutrophil proportion, neutrophil/lymphocyte ratio, and the circulating levels of interleukin-6, C-reactive protein, and procalcitonin were higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocyte count in pneumonia patients did not recover when discharged.

Conclusions

Older age and higher levels of C-reactive protein, procalcitionin, interleukin-6, and lactate might predict COVID-19 progression. T lymphocyte, especially CD8+ cell-mediated immunity is critical in recovery of COVID-19. This study may help in predicting disease progression and designing immunotherapy for COVID-19.
Pharmacodynamic and pharmacokinetic behavior of landiolol during dobutamine challenge in healthy adults
Authors: Krumpl Günther , Ulč Ivan , Trebs Michaela , Kadlecová Pavla , Hodisch Juri
Published: November 2020

Background

To study the pharmacokinetic and -dynamic behavior of landiolol in the presence of dobutamine in healthy subjects of European ancestry.

Methods

We conducted a single-center, prospective randomized study in 16 healthy subjects each receiving an infusion of dobutamine sufficient to increase heart rate by 30 bpm followed by a 60 min infusion of 10 μg/kg/min landiolol.

Results

Dobutamine-induced increases in heart rate were stable for at least 20 min before a 60 min landiolol- infusion was started. The dobutamine effects were rapidly antagonized by landiolol within 16 min. A further slight decrease in heart rate during 20–60 min of the landiolol infusion occurred as well. Upon termination of landiolol infusion, heart rate and blood pressure recovered rapidly in response to the persisting dobutamine infusion but did not return to the maximum values before landiolol infusion. The pharmacokinetic parameters of landiolol in presence of dobutamine showed a short half-life (3.5 min) and a low distribution volume (0.3 l/kg). No serious adverse events were observed.

Conclusion

Landiolol can antagonize the dobutamine-induced increases in heart rate and blood pressure in a fast way. A rapid bradycardic effect until steady-state plasma levels is followed by a slow heart rate reduction. The latter can be attributed to an early desensitization to dobutamine. Consequently, after termination of landiolol, the heart rate did not achieve maximum pre-landiolol values. The pharmacokinetics of landiolol during dobutamine infusion are similar when compared to short- and long-term data in Caucasian subjects. Landiolol in the given dose can thus serve as an antagonist of dobutamine-induced cardiac effects.

Trial registration

Registration number 2010–023311-34 at the EU Clinical Trials Register, registration date 2010-12-21.
Optimization of dyeing parameters of cotton standardized samples for laundry test of dye transfer inhibition program
Authors: Guo Mingqi , Jiang Li , Yang Qingbo , Sun Chang , Liu Jianli , Gao Weidong
Published: November 2020

In order to prevent light-colored clothes from being stained by dyes released from dark clothes during the washing process, some new-type washing machines have developed the dye transfer inhibition washing program. However, there is no certified reference materials for the test of dye transfer inhibition function. To this end, cotton fabric and reactive dyes are used as experimental materials to prepare standardized samples to evaluate the dye transfer inhibition function of washing machines. Firstly, the single factor analysis method is used to analyze the significance of the dyeing parameters including dye dosage, dyeing temperature, sodium sulfate dosage and sodium carbonate dosage. Secondly, a 4-factor 5-level experimental design and theoretical prediction of the best dyeing parameters are successively carried out through central composite design and response surface method. Two evaluation indicators, the dye release amount of the standardized sample of dyed fabric and the color difference value of the standardized sample of white fabric after washing, are proposed as the response values for response surface analysis to search the optimal dying parameters in theory. The optimal dyeing parameters obtained through response surface analysis are that the dosage of dye is 5.63% (owf), the dyeing temperature is 60 °C, the dosage of sodium sulfate is 93.60 g/L, and the dosage of sodium carbonate is 15 g/L. Experimental results indicate that the standardized samples prepared with optimal dyeing parameters can effectively distinguish the dye transfer inhibition function of washing machines.
Lumbar spine abnormalities and facet joint angles in asymptomatic elite junior tennis players
Authors: Connolly Molly , Rotstein Andrew H. , Roebert Justin , Grabinski Rafal , Malara Frank , O’Shea Tomas , Wood Tim , Omizzolo Melanie , Kovalchik Stephanie , Reid Machar
Published: November 2020

Background

Lumbar spine abnormalities, in particular stress fractures to the pars interarticularis, are common in elite junior tennis players, though the difference in prevalence between males and females remains unclear. Further, facet joint orientation appears to be a possible option for recognizing which players might go on to present with a pars stress fracture. Given the link between pars stress fractures and low back pain in tennis players, it appears logical to explore the link between facet joint angle and pars abnormalities. Thus, the purpose of this study was to describe the prevalence of lumbar spine abnormalities and explore the relationship between facet joint orientation and pars abnormalities in elite adolescent tennis players.

Methodology

Lumbar spine MRI images of 25 elite junior tennis players were obtained and distributed between five radiologists for analysis. Descriptive comparisons and confidence intervals were used to describe the prevalence of the abnormalities. A generalized linear regression model was conducted to investigate the relationship between lumbar pars abnormalities and lumbar facet joint angles.

Results

Sixteen (64%) of 25 players were found to have at least one lumbar spine abnormality. Pars abnormalities affected 36% of players while bone marrow edema was found in 24% of players. Disc herniation, disc degeneration, and facet joint degeneration were diagnosed in 20%, 44%, and 24% of players respectively. Lastly, one player (4%) was diagnosed with spondylolisthesis. Females had significantly larger facet joint angles across L3/4 L5/S1 compared to males (p < 0.01). Further, those who had pars abnormalities had larger facet joint angles compared to those who did not (p < 0.001).

Conclusion

Disc degeneration, pars abnormalities, including bone marrow edema, and facet joint degeneration were common findings among elite adolescent tennis players.

Additionally, this study is the first to discover that pars abnormalities are linked to facet joint angle in elite adolescent tennis players. This finding might assist in identifying tennis players at a greater risk of developing lumbar spine pars abnormalities in the future.
Effect of different surface treatments on shear bond strength of ceramic brackets to old composite
Authors: Farhadifard Homa , Rezaei-Soufi Loghman , Farhadian Maryam , Shokouhi Parisa
Published: November 2020

Background

At present, the demand for orthodontic treatment is on the rise. On the other hand, evidence shows that the bond strength of composite resins to old composite restorations is often unreliable. Therefore, the aim of this in vitro study was to assess the effect of different surface treatments on shear bond strength (SBS) of ceramic brackets to old composite restorations.

Methods

In this in vitro experimental study, 60 nano-hybrid composite discs were fabricated. For aging, the discs were incubated in deionized water at 37 °C for 1 month. Next, they underwent 4 different surface treatments namely acid etching with 37% phosphoric acid, sandblasting, grinding, and Er,Cr:YSGG laser irradiation. Ceramic brackets were then bonded to the discs and underwent SBS testing.

Results

The maximum mean SBS value was obtained in the grinding group (9.16 ± 2.49 MPa), followed by the sandblasting (8.13 ± 2.58 MPa) and laser (6.57 ± 1.45 MPa) groups. The minimum mean SBS value was noted in the control group (5.07 ± 2.14 MPa).

Conclusion

All groups except for the control group showed clinically acceptable SBS. Therefore, grinding, sandblasting, and Er,Cr:YSGG laser are suggested as effective surface treatments for bonding of ceramic orthodontic brackets to aged composite.
Human reliability analysis in maintenance team of power transmission system protection
Authors: Tavakoli Mehdi , Nafar Mehdi
Published: November 2020

The requirement for reliable electrical energy supply increases continuously because of its vital role in our lives. However, events due to various factors in the power grid can cause energy supply to be interrupted. One of these factors is human error and thus human reliability analysis is a serious element in the industry. The first step is to identify the roots of human error, on which there has been limited research in this area. In this paper, the potential and actual causes of human error in maintenance teams of power transmission system protection are identified and predicted within a framework of human factors analysis and classification system method. Then, human error factors are ranked to help improve human reliability. The proposed method is implemented in the Fars Electricity Maintenance Company.