bluuebunny/crossref_metadata_2025 huggingface dataset:
The voltage-gated proton channel Hv1 contributes to neuronal injury and motor deficits in a mouse model of spinal cord injury
Authors: Murugan Madhuvika , Zheng Jiaying , Wu Gongxiong , Mogilevsky Rochelle , Zheng Xin , Hu Peiwen , Wu Junfang , Wu Long-Jun
Published: August 2020

Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated proton channel, Hv1, functionally expressed in microglia has been implicated in microglia polarization and oxidative stress in ischemic stroke. Here, we investigate whether Hv1 mediates microglial/macrophage activation and aggravates secondary damage following spinal cord injury (SCI). Following contusion SCI, wild-type (WT) mice showed significant tissue damage, white matter damage and impaired motor recovery. However, mice lacking Hv1 (Hv1-/-) showed significant white matter sparing and improved motor recovery. The improved motor recovery in Hv1-/- mice was associated with decreased interleukin-1β, reactive oxygen/ nitrogen species production and reduced neuronal loss. Further, deficiency of Hv1 directly influenced microglia activation as noted by decrease in microglia numbers, soma size and reduced outward rectifier K+ current density in Hv1-/- mice compared to WT mice at 7d following SCI. Our results therefore implicate that Hv1 may be a promising potential therapeutic target to alleviate secondary damage following SCI caused by microglia/macrophage activation.
The Complete Chloroplast Genome of Tamarix Ramosissima and Comparative Analysis of Tamaricaceae Species 
Authors: Wang Le , Wang Li , Guo Zhihong
Published: August 2020

Background: Tamarix ramosissima is a deciduous shrub resided in arid and semi-arid regions. Although of ecological and medicinal values, some Tamarix species are considered invasive as they have dominated the riparian zones of dryland in some parts of the world. Chloroplast (cp) DNA is highly conserved in structure and gene arrangement, making cp genomic data valuable resources for species delimitation and phylogenetics. The cp genome of T. ramosissima was de novo assembled with the aim of providing reference and data resource for further cp-derived marker development and species delimitation of Tamarix.Results: Here, the complete chloroplast (CP) genome of T. ramosissima was sequenced and analyzed, showing a size of 156150 bp and a GC content of 36.5%. The plastome displayed a typical quadripartite structure, consisting of a pair of inverted repeat (IR) regions of 26554 bp, separated by a large single copy (LSC) region of 84795 bp, and a small single copy (SSC) region of 18247 bp. The cp genome encoded 130 genes, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. A total of 32 repeat sequences and 64 simple sequence repeats (SSR) were identified in the plastome, and an obvious A/T bias was observed in the majority of the SSRs detected. By comparing the T. ramosissima cp genome with those of four other Tamaricaceae species, a number of divergence hotspots were identified among these plastomes. Together with the SSRs and long repeats identified, these divergence hotspots could be developed as potential molecular markers facilitating species discrimination and evolutionary studies. Using plastome sequences, we re-investigated the phylogenetic relationship among 19 species, and T. ramosissima was found to be a sister of Tamarix chinensis.Conclusions: Taken together, our study provides valuable genomic resources to deepen the understanding of the plant photosynthetic mechanism and phylogenomics.
Validity and Reliability of the Portuguese-performance Assessment of Self-care Skills (P-PASS) for Portuguese Individuals With Disabilities
Authors: Ferreira Pedro L , Simões Ana Lúcia , Dourado Marília , Holm Margo B. , Rogers Joan C.
Published: August 2020

Background: Due to the increasing need to measure health outcomes and to ensure a more independent life, it is essential to validate instruments capable of assessing the functionality of activities of daily living. The Performance Assessment of Self-Care Skills (PASS), based on three assessment parameters (independence, safety and adequacy), allows health professionals to delineate their interventions more effectively according to the needs of each client. The purpose of this study was to create a Portuguese version of the PASS (P-PASS) and to measure the performance of people with disabilities. Methods. Linguistic validation was performed through the translation/back-translation procedure. Next, the scale to be completed by health professionals was submitted to a clinical review by a panel of experts. Subsequently, it was applied to 98 people with physical and/or cognitive disabilities. The data collected were then analyzed and the results evaluated in accordance with the three PASS parameters. The results were also analyzed in terms of age and gender. Results. To create the Portuguese version, one task was removed from the original PASS and seven tasks were combined or adapted. Task independence had the highest scores and adequacy the lowest. In terms of reliability, the P-PASS revealed almost perfect levels of agreement between observers, except for the adequacy parameter of the ‘bed mobility’ task that showed moderate agreement. In general, the original structure of the PASS was replicated in the Portuguese version. Men presented greater independence than women in the tasks of ‘bill paying by ATM’ and ‘changing TV command batteries.’ Participants under 60 years of age had the highest scores overall. Conclusions. The combination or adaptation of some items to be more culturally relevant is a valid procedure that has been used by other authors during the validation of PASS items. The results obtained by P-PASS showed comparable scores with the original PASS and with other translated/adapted versions. The P-PASS is a valid and reliable scale for the Portuguese population, enabling more effective measurement of health outcomes.
si-SNHG5-FOXF2 Inhibits TGF-β1-induced Fibrosis in Human Primary Endometrial Stromal Cells by Wnt/β-catenin Signaling Pathway
Authors: Liu Limin , Chen Guobin , Chen Taoliang , Shi Wenjuan , Hu Haiyan , Song Kaijing , Huang Ruichun , He Yuanli , Cai Huihua
Published: August 2020

Background: Intrauterine adhesions (IUAs) are manifestations of endometrial fibrosis characterized by inflammation and fibrinogen aggregation in the extracellular matrix (ECM). The available therapeutic interventions for IUA are insufficiently effective in the clinical setting for postoperative adhesion recurrence and infertility problems. In this study, we investigated si-SNHG5-FOXF2 can serve as a molecular mechanism for inhibition of IUA fibrosis ex vivo.Methods: FOXF2, TGF-β1 and collagens expression levels were measure by a Microarray sequencing analysis in three normal endometrium group and six IUA patients. We induced primary HESCs into MFs to develop an IUA cell model with various concentrations of TGF-β1 at various times. Downstream target genes for FOXF2 were screened by chromatin immunoprecipitation combined with whole- genome high-throughput sequencing (ChIP-seq). We investigated ECM formation, cell proliferation and Wnt/β-catenin signaling pathway-related proteins in primary HESCs with FOXF2 downregulation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting (WB), immunohistochemistry (IHC), Flow cytometry, EdU and CCK8 assays. We identified lncRNA SNHG5 as the upstream regulatory gene of FOXF2 through RNA immunoprecipitation (RIP), RNA-pulldown and FISH. Finally, we examined FOXF2 expression, ECM formation, cell proliferation and Wnt/ β-catenin signaling pathway-related proteins in primary HESCs with FOXF2 downregulation.Results: FOXF2 was highly expressed in endometrium from patients with IUA. Treatment of primary HESCs with 10ng / ml TGF-β1 for 72 h was found to be most effective for developing an IUA cell model. FOXF2 regulated multiple downstream target genes including collagen, VIM and cyclin D2/DK4 by ChIP-seq and ChIP-PCR. FOXF2 downregulation inhibited TGF-β1-mediated primary HESC fibrosis including ECM formation, cell proliferation and Wnt/β-catenin signaling pathway-related proteins expressions. We identified lncRNA SNHG5 as an upstream gene that directly regulated FOXF2 by RIP-seq, qRT-PCR, WB and FISH. SNHG5 downregulation suppressed FOXF2 expression in the IUA cell model, resulting in synergistic repression of Wnt/β-catenin signaling pathway activation and thereby altering TGF-β1-mediated ECM aggregation in endometrial stromal cells ex vivo. Conclusions: Regulation of the Wnt/β-catenin signaling pathway and ECM formation by si-SNHG5-FOXF2 effectively inhibited the profibrotic effect of TGF-β1 on primary HESCs. It can provide a molecular basis for antagonizing TGF-β1-mediated fibrosis in primary HESCs.
Development of the Gait Outcomes Assessment List for Lower Limb Differences (GOAL-LD) Questionnaire: A Patient and Parent Reported Outcome Measure for Pediatric Lower-limb Deformity
Authors: Dermott Jennifer A , Wright Virginia , Salbach Nancy M , Narayanan Unni G
Published: August 2020

Purpose: To develop a priority-based patient /parent reported outcome measure for children with lower-limb differences (LD) by adapting the Gait Outcomes Assessment List (GOAL) questionnaire. Methods: Guided by a conceptual framework of patient priorities, the GOAL questionnaire was iteratively modified and its sensibility evaluated by field-testing it on children with LD and their parents. Cognitive interviews were conducted with a subgroup of these children, and an e-survey administered to a multidisciplinary group of health care professionals with expertise in paediatric LD. Findings were integrated to create the final version of the GOAL-LD. Results: Twenty-five children, 20 parents, and 31 healthcare professionals evaluated the content and sensibility of the GOAL, with an emphasis on the relevance and importance of the items to patients’ health related quality of life (HRQL). This resulted in the retention of 26 of the original 50 items, elimination of 12, modification of 12, and addition of seven new items. The new 45-item GOAL-LD questionnaire was shown to be sensible and its content deemed important. Conclusion: The GOAL-LD questionnaire has a high level of face and content validity, and sensibility. It comprehensively captures the HRQL goals and outcomes that matter to children with LD and their parents. Following further psychometric evaluation, the GOAL-LD may serve as a much needed patient and parent reported outcome measure for this population.
Modified Silicone Stent in the Treatment of Bronchopleural Fistula: Clinical Observation of 17 Cases
Authors: Zeng Junli , Wu Xuemei , Chen Zhide , Zhang Meihua , Ke Mingyao
Published: August 2020

Objective: Bronchopleural fistula is a rare but life-threatening event with limited therapeutic options. Aim of our study is to investigate the efficacy and safety of the modified silicone stent in patients with bronchopleural fistula.Method: Between March 2016 and April 2020, we retrospectively collected 17 patients with bronchopleural fistula and who underwent bronchoscopic placement of the modified silicone sten. The Y-shaped stent was tailored and sutured manually. The initial success, clinical success, the cured rate and complications were recorded. Results: Placement of the modified silicone stent was successful in 16 patients on first attempt (initial success rate was 94.1%). The median follow-up time was 107(rang, 5-431) days. The amelioration of respiratory symptoms was reported in all patients. There were 14 patients with empyema, the daily drainage was significantly decreased in 11 patients over time, and the purulent fluid completely disappeared in six patients. The clinical success rate was 76.5%. There were seven stents was removed during follow-up, four (26.7%) removed for cured fistula, two for the severe proliferation of granulation tissue and one for the dislocation of stent. No severe adverse events of stent migration and suture dehiscence happened. There were three cases were lost to follow-up and seven patients succumbed. The cause of death included progression of primary malignance, the uncontrolled infection, myocardial infarction and left heart failure.Conclusion: The modified silicone stent may be an effective and safe option for bronchopleural fistula patients in whom the conventional therapy is inappropriate and contraindicated.
Triple Stapling Resection and J pouch anal Stapling Anastomosis for Ulcerative Colitis
Authors: Kawahara Hidejiro , Omura Nobuo , Akiba Tadashi
Published: August 2020

Background: In 2017, we reported laparoscopic total proctocolectomy with J pouch anal anastomosis, which was created at the dentate line by our original procedure using staplers, Triple Stapling Resection and J pouch Anal Stapling Anastomosis (TSRJASA), for ulcerative colitis (UC) patients. UC patients have undergone TSRJASA since it was introduced in our institution. However, the feasibility and usefulness of TSRJASA for UC patients has not been elucidated.Methods: From January 2014 to December 2018, fourteen patients with ulcerative colitis, including three cases of concomitant cancer, who underwent TSRJASA were enrolled in this study. Anal manometry was performed using the Pock Monitor GMMS-100 system (STAR MEDICAL, INC., Tokyo, Japan) one year and two years after surgery. Maximum resting pressure, maximum squeeze pressure, and the length of the high-pressure zone were measured. Fecal incontinence was evaluated using the Wexner incontinence questionnaire.Results: J pouch anal anastomosis was created at the dentate line in all patients. In a manometric examination two years after surgery, maximum resting pressure was 75.3 (54-88) mmHg, maximum squeeze pressure was 125.0 (90-160) mmHg, and the length of the high-pressure zone was 39.6 (35-42) mm. Wexner score was 2.8 (1-4).Conclusion: TSRJASA seems to be a useful procedure for UC patients given its acceptable defecation function.
D-dimers at hospital admission for COVID-19 are associated with in hospital mortality independently of venous thromboembolism: Insight from a French multicenter cohort study
Authors: Chocron Richard , Duceau Baptiste , Gendron Nicolas , Ezzouhairi Nacim , Khider Lina , Trimaille Antonin , Goudot Guillaume , Weizman Orianne , Alsac Jean Marc , Pommier Thibault , Bory Olivier , Cellier Joffrey , Philippe Aurélien , Geneste Laura , Abdallah Iannis Ben , Panagides Vassili , Batti Salma El , Marsou Wassima , Juvin Philippe , Deney Antoine , Messas Emmanuel , Attou Sabir , Planquette Benjamin , Mika Delphine , Gaussem Pascale , Fauvel Charles , Diehl Jean-Luc , Pezel Theo , Mirault Tristan , Sutter Willy , Sanchez Olivier , Bonnet Guillaume , Cohen Ariel , Smadja David M.
Published: August 2020

Background: Coronavirus disease 2019 (COVID-19) has been associated with coagulation disorders, in particular high levels of D-dimers, and increased frequency of venous thromboembolism (VTE). We explore the association between D-dimers at admission and in-hospital mortality in hospitalized COVID-19 patients with or without symptomatic VTE.Methods: From February 26 to April 20, 2020, D-dimer level at admission and outcomes of patients hospitalized for COVID-19 in medical wards (in-hospital mortality or VTE) were retrospectively analyzed in a multicenter study in 24 French hospitals.Results: Among 2878 patients enrolled in the study, 1154 (40.9%) patients had D-dimer measurement at admission. A receiver operating characteristic (ROC) curve analysis identified D-dimer level above 1128 ng/mL as the optimum cutoff value to predict in-hospital mortality (Area Under the Curve of 64.9% (95% CI 0.60–0.69) with a sensitivity of 71.1% (95% CI 0.62–0.78) and a specificity of 55.6% (95% CI 0.52–0.58) that not differ in the subgroup of patients with VTE during hospitalization. Among 609 (52.8%) patients with D-dimers level < 1128 ng/mL at admission, only 35 (5.7%) deaths occurred during hospitalization. After adjustment, in a cox proportional hazard and logistic regression models, D-dimers above 1128 ng/mL at admission were also associated to a worth prognosis with a OR of 3.07 (95% CI 2.05–4.69, p < 0.001) and an unadjusted hazard ratio of 2.11 (95%CI 1.31–3.4, p < 0.01).Conclusions: D-dimer level over 1128 ng/mL is a relevant predictive factor for in-hospital mortality in COVID-19 hospitalized patients in medical ward, regardless the occurrence of VTE during hospitalization.
A Comprehensive Analysis of Protein Data Bank reveals Low Desolvation Penalty in π-Cation System
Authors: Yang Jing-Fang , Wang Meng-Yao , Wang Di , Li Jing-Yi , Hao Ge-Fei , Li Qing X. , Yang Guang-Fu
Published: August 2020

Cation-π interactions widely exist between ligand-protein interfaces, attracting much attention in molecular recognition in recent years. Interactions named cation-π and π-cation (cationic vs arene small molecular ligands) shall be separately considered in drug and pesticide design process. The two interactions involved in ligands and protein pockets may differ in energy features and therefore offers significant inspiration for drug and pesticide design. However, an in-depth study on differences between cation-π and π-cation systems from an energy perspective is still lacking. In this study, we calculated and compared cation-π and π-cation systems in terms of physicochemical properties of ligand/protein and solvation effect. It seems that the desolvation penalty of the cation-π systems was relatively higher than the π-cation pairs, even though these interactions both can improve the ligand activity. This is the reason for evolution converged on π-cation interactions in the cation-π-mediated proteins. The π-cation interaction facilitating the inhalation of ligand to the pocket may provide a new sight for the molecular design of pharmaceuticals and pesticides.
Quality of Life in Women With Postmenopausal Osteoporosis - Pilot Studies in the Łódź Province
Authors: Górczewska Bogumiła , Jakubowska-Pietkiewicz Elżbieta
Published: August 2020

The authors have requested that this preprint be removed from Research Square.
Multidimensional Item Response Theory to Assess Psychological Properties of GHQ-12 in School Children Parents
Authors: Haem Elham , Doostfatemeh Marziyeh
Published: August 2020

Background: Multidimensional item response theory (MIRT) model provides an ideal foundation to assess psychological properties of a questionnaire designed with multidimensional structure. This study aims to present the first use of MIRT models to investigate psychological properties of GHQ-12. Methods: A total of 1104 school children parents completed the Persian version of GHQ-12 questionnaire. A MIRT model was applied to model observed scores for each GHQ-12 item as a function of the subject’s latent traits while taking into account the correlation between dimensions of the questionnaire. The goodness of fit indices were reported and items fit were assessed. Individual items were described in detail through item characteristic curves and the amount of information carried by different items were presented using information curves. Results: The MIRT analysis of the 12 item GHQ successfully demonstrated two factor structure corresponding to psychological distress and social dysfunction. The model showed all items were fitted adequately. Items varied in their discrimination ranged from 0.86 to 2.35 and 1.18 to 2.41 for psychological distress and social dysfunction, respectively. Moreover, item 8 and item 2 provided the least information in psychological distress and social dysfunction dimensions, respectively. Conclusions: The developed framework to evaluate psychological properties of GHQ-12 can be a suitable alternative to traditional approaches and also unidimensional IRT models which its use have been restricted due to multidimensional structure of the questionnaire.
Predicting Quality of Life and Mental Health During the First Year After Trauma Using Radial Basis Function Neural Network 
Authors: Sehat Zahra , Fakharian Esmaeil , Sehat Mojtaba , Omidi Abdollah
Published: August 2020

Background: This study aimed to investigate the quality of life (QOL) and mental health (MH) post-trauma in the population over 15 years. Methods: A cross-sectional population-based study, the cluster sampling method was used and 3880 people were interviewed randomly selected individuals between over 15 years in each household in the city of Kashan. Data were analyzed using chi-square, t-test. After data collection, a radial basis function neural network (RBFNN) architecture is exploited to predict the QOL category and MH status after traumatic injuries. Results :The rate of trauma was 70.64 (62.60-78.70) in 1000 annually, and 77.73% were male. 38.3% of people with trauma have suspected of having mental disorder and 53.3% of people with injury were in good condition of QOL. The risk of suspected MH disorders in people with trauma during the last year was 1.2(0.96-1.61), and the risk of bad QOL was 2.6(1.8-3.7). The obtained results reveal that the RBFNN model can predict the QOL category and MH status with a high level of accuracy (maximum 1% predicting error). Conclusion :This study reveals several parameters associated with the MH and QOL after trauma. This parameter can be used in prediction outcomes and used to evaluate the care of people with injury. It can also be concluded that the RBFNN predictor can be used for predicting the QOL category and MH status with reasonable authenticity, efficiency, and accuracy.
Age-Specific Crisis Awareness Survey for Coronavirus Disease 2019 (COVID-19): How Much Do You Think You Should Pay for Hypothetical Prophylactic Vaccine and Therapeutic Drug for COVID-19?
Authors: Kawahara Takashi , Yao Masahiro , Uemura Hiroji
Published: August 2020

BACKGROUND: The spread of coronavirus disease 2019 (COVID-19) has been a worldwide phenomenon with 2,063,161 people infected and 136,938 deaths globally as of April 16, 2020. This study conducted a chronological survey of crisis awareness regarding COVID-19 within different age groups.METHODS: An internet-based survey was performed of healthy Japanese adults to investigate the value of a hypothetical prophylactic vaccine and therapeutic drug for COVID-19 in each age group. The survey was conducted on Friday of each week commencing from February 14, 2020 to April 10, 2020. At certain times or events such as when the government released major announcements or when there was a rapid increase in the number of infected individuals, a similar survey was conducted on an additional 1,200 individuals per week.RESULTS: A total of 12 surveys, including weekly surveys spanning over 9 weeks, were conducted, and a total of 19,113 samples from 12,254 individuals were obtained. The mean price for a hypothetical prophylactic vaccine was 2876.3 JPY (26.9 USD) at the first survey and was significantly increased to 3357.4 JPY (31.4 USD) for the most recent survey (p < 0.0001). CONCLUSIONS: Though the percentage of those who will not pay were higher in young age group than in elderly age group, the percentage of those who will pay more than standard costs of influenza vaccine or treatment drugs were same between each aging group.
Adolescent-Caregiver Relationships and Mental Health Outcomes Among Adolescents Living with HIV: A Prospective Cohort Study in South Africa
Authors: Shenderovich Yulia , Boyes Mark , Esposti Michelle Degli , Casale Marisa , Toska Elona , Roberts Kathryn J. , Cluver Lucie
Published: August 2020

Background Mental health problems may impact adherence to anti-retroviral treatment, retention in care, and consequently the survival of adolescents living with HIV. The adolescent-caregiver relationship is an important potential source of resilience. However, there is a lack of longitudinal research in sub-Saharan Africa on which aspects of adolescent-caregiver relationships can promote mental health among adolescents living with HIV. We draw on a prospective longitudinal cohort study undertaken in South Africa to address this question.Methods The study traced adolescents aged 10-19 initiated on antiretroviral treatment in government health facilities (n = 53) within a health district of the Eastern Cape province. The adolescents completed standardised questionnaires during three data collection waves between 2014 and 2018. We used within-between multilevel regressions to examine the links between three aspects of adolescent-caregiver relationships (caregiver supervision, positive caregiving, and adolescent-caregiver communication) and adolescent mental health (depression symptoms and anxiety symptoms), controlling for potential confounders (age, sex, rural/urban residence, mode of infection, household resources), n=926 adolescents. Results Improvements in caregiver supervision were associated with reductions in anxiety (0.98, 95% CI 0.97-0.99, p=0.0002) but not depression symptoms (0.99, 95% CI 0.98-1.00, p=.151), while changes in positive caregiving were not associated with changes in mental health symptoms reported by adolescents. Improvements in adolescent-caregiver communication over time were associated with reductions in both depression (IRR=0.94, 95% CI 0.92-0.97, p<.0001) and anxiety (0.91, 95% CI 0.89-0.94, p<.0001) symptoms reported by adolescents. Conclusions Findings highlight open and supportive adolescent-caregiver communication and good caregiver supervision as potential factors for guarding against mental health problems among adolescents living with HIV in South Africa. Several evidence-informed parenting programmes aim to improve adolescent-caregiver communication and caregiver supervision, and their effect on depression and anxiety among adolescents living with HIV should be rigorously tested in sub-Saharan Africa. How to improve communication in other settings, such as schools and clinics, and provide communication support for caregivers, adolescents, and service providers through these existing services should also be considered.
Assessment of Acute Mountain Sickness: How to integrate the advantages of the Lake Louise Score and the Chinese AMS Score
Authors: Wu Yu , Li Peng , Zhong Zhifeng , Xie Jiaxin , Zhou Simin , Gao Yuqi , Chen Jian
Published: August 2020

Aims: To compare the differences in acute mountain sickness (AMS) incidence between two AMS diagnostic scoring criteria, including the Lake Louise Score and the Chinese AMS Score. Methods: A total of 2486 young men completed questionnaires after flying from Chendu (500 m) to Lasha (3658 m). The AMS incidence was investigated using a questionnaire that contained the scoring criteria for the LLS and CAS. To determine the grouping of all the symptoms on the AMS questionnaire, a systematic cluster analysis and two-step cluster analysis were used to analyse various symptoms and cases separately.Results: The AMS incidence was 37.5% (n = 932) according to the LLS, in which the cut-off point depended on headache and a total score ≥ 3, and 59.3% (n = 1473) according to the CAS, in which the cut-off point depended on headache, vomiting or a total score ≥ 5. The LLS and CAS outcomes had a significant positive correlation (Spearman’s rho = 0.918, P < 0.05) and were moderately consistent (kappa value = 0.488, P < 0.001). The positive AMS incidence determined by the CAS was significantly higher than that by the LLS (P < 0.001). Compared with the LLS, the sensitivity was 100%, the specificity was 65.23%, the positive predictive value was 63.34%, and the negative predictive value was 100% for the CAS in the diagnosis of AMS. The CAS identified all AMS subjects diagnosed by the LLS, and an additional 541 subjects. Of all the symptoms investigated, the dominant symptoms were fatigue (59.3%), dizziness (55.0%), headache (50.6%), chest tightness (40.4%), and shortness of breath (37.2%), and the last two symptoms were not included in the LLS. The cluster analysis show that chest distress, shortness of breath and palpitations were relatively independent of the major symptoms assessed by the LLS. Conclusion: The CAS had testing characteristics for diagnosing AMS similar to those of the Lake Louise Questionnaire Score, and the CAS diagnosed a higher prevalence of AMS than the LLS. It is suggested that chest distress and shortness of breath should be paid adequate attention and taken into account in AMS diagnostic criteria in the next revision to better diagnosis and study AMS.
Thawed Cryopreserved Synovial Mesenchymal Stem Cells Show Comparable Effects to Cultured Cells in the Inhibition of Osteoarthritis Progression in Rats
Authors: Horiuchi Kiyotaka , Ozeki Nobutake , Endo Kentaro , Mizuno Mitsuru , Katano Hisako , Akiyama Masako , Tsuji Kunikazu , Koga Hideyuki , Sekiya Ichiro
Published: August 2020

Background Intra-articular injections of mesenchymal stem cells (MSCs) can inhibit the progression of osteoarthritis (OA) in animal studies. Previous reports have used cultured MSCs, but the ability to use thawed cryopreserved MSC stocks would be highly advantageous. Our purpose was to elucidate whether thawed cryopreserved MSCs show comparable inhibitory effects on OA progression in rats to those obtained with cultured MSCs. Methods Cultured rat synovial MSCs or thawed MSCs were compared for in vitro viability and properties. The activity of synovial MSCs derived from rats expressing luciferase was compared by the luminescence intensity both in vitro and in vivo. The inhibitory effect of cultured MSCs on OA progression was evaluated by injecting PBS and cultured MSCs into the right and left knees, respectively, of the same individual meniscectomized rats. A similar test evaluated cryopreservation fluid (95% FBS with 5% DMSO; termed the 95% FBS group) versus thawed MSCs. Cartilage degeneration was assessed at 4 and 8 weeks using gross finding and histological scores. The results were used to set the primary outcome and sample size. Cultured MSCs were then injected into one knee and thawed MSCs into the contralateral knee of the same individual to compare their effects.Results Cultured MSCs and MSCs thawed after cryopreservation in 95% FBS with 5% DMSO had comparable in vitro viability, colony formation, and chondrogenic potential. The luminescence intensity was comparable between the two MSC preparations. In the rat OA model, the gross findings and histological scores for tibial cartilage did not differ at four weeks but were significantly lower in the cultured MSC group than in the PBS group and significantly lower in the thawed MSC group than in the 95% FBS group at eight weeks. These results established the tibial cartilage histological score at eight weeks as the primary outcome and a sample size of nine for comparing cultured versus thawed MSCs. The tibial cartilage histological scores did not differ significantly at eight weeks after injection of cultured and thawed MSCs into the opposite knees of the same individuals.ConclusionsThawed MSCs showed comparable inhibitory effects on OA progression to cultured MSCs.
Proanthocyanidins Induce miR-133b Expression to Promote Ischemic Skeletal Muscle Regeneration by Targeting MKP1
Authors: Chen Shi , Du Chao , Pan Lilong , Yang Qian , Yu Peihe , Wu Fei , Zhou Yang , Hai Rui , Zhang Chunxiang , Zhou Xiangyu
Published: August 2020

Background: Limb ischemic necrosis is mainly attributed to peripheral arterial disease (PAD). Reducing oxidative stress and promoting damaged skeletal muscle regeneration may be benefit for ischemic limb treatment. Proanthocyanidins (PC) is a powerful antioxidant and free radical scavenger, but little is known about its role and related molecular mechanism in limb ischemic injury. The current study was undertaken to explore its role in the damaged skeletal muscle regeneration both in vitro and vivo, and whether MicroRNAs (miRNAs) involved in this process. Methods: The potential effects of PC on the damaged muscle regeneration were explored in human skeletal muscle satellite cells (HSKMSCs) under hypoxic-ischemic condition and in mice limb ischemia model, then, aberrant expression of miRNAs in ischemic skeletal muscles were determined by microarray analysis, and regulatory mechanism of the specific miRNA on HSKMSCs myogenic differentiation was further investigated by gain and loss of functional experiments. Additionally, the direct target gene was examined by luciferase reporter assay.Results: In mice limb ischemia model, our results revealed that PC reduced oxidative stress level, significantly promoted ischemic limb damaged muscle regeneration and motor function recovery, then, aberrant expression of miRNAs in ischemic skeletal muscles were determined by microarray analysis, combine with the results of the RT-qPCR, the miR-133b-3p was proved to be the specific miRNA. In vitro, our results revealed that PC induced the overexpression of miR-133b to activate the p38-MAPK signal pathway and increased the myogenic differentiation-related molecules expression, which eventually promoted myotubes formation. Furthermore, MKP1 was confirmed a direct target gene of miR-133b.Conclusion: Our results suggest that PC display skeletal muscle protective properties that are mediated by miR-133b /MKP1/ p38-MAPK signal axis, offering a novel therapeutic opportunity for limb ischemic injury.
Prevalence and Characteristics of Cutaneous Allodynia in Migraine and Probable Migraine: A Population-Based Study
Authors: Han Seung Min , Kim Kyung Min , Cho Soo-Jin , Yang Kwang Ik , Kim Daeyoung , Yun Chang-Ho , Chu Min Kyung
Published: August 2020

Background: Cutaneous allodynia (CA) is a common feature of migraine and a clinical marker of central sensitization. Probable migraine (PM) is a subtype of migraine that fulfils all but one criterion of migraine. The present study aimed to evaluate the prevalence and characteristics of CA and those of migraine in PM. Methods: We used the data of the Korean Sleep-Headache study, which was a nation-wide population-based study on headache and sleep. CA was evaluated using the Allodynia Symptom Checklist-12 (ASC-12) questionnaire with ASC-12 score ≥ 3 classified as CA. Results: Of 2501 participants, the prevalence of migraine and PM were 5.0% and 11.6%, respectively. The prevalence of CA did not significantly differ between migraine and PM (16.0% vs. 14.5%, respectively, p = 0.701). Individuals with PM with CA reported a higher monthly frequency of headache (3.3 ± 4.3 vs. 1.8 ± 3.6, respectively, p = 0.044), more severe intensity of headache (Visuals Analogue Scale, median and interquartile range, 6.0 [4.0–7.0] vs. 5.0 [3.0–6.0], respectively, p = 0.002), and higher impact of headache (Headache Impact Test-6, 56.3 ± 7.2 vs. 48.3 ± 8.0, respectively, p < 0.001) and disability (Migraine Disability Assessment, 1.00 [0.00–10.00] vs. 0.00 [0.00–1.00], respectively, p < 0.001) than individuals with PM without CA. Multiple regression analyses revealed that the frequency and intensity of headache, anxiety, and depression were significant factors of CA in individuals with PM. Conclusions: Approximately one-sixth of individuals with migraine and PM experienced CA in a representative sample of Korea. Anxiety, depression, and high frequency of headaches were significant factors of CA in individuals with PM.
Knockdown of nrf2 exacerbates TNF-α-induced proliferation and invasion of rheumatoid arthritis fibroblast-like synoviocytes through activating JNK pathway
Authors: Du Yu , Wang Qian , Tian Na , Lu Meng , Zhang Xian-Long , Dai Sheng-Ming
Published: August 2020

Background.

Fibroblast-like synoviocytes (FLS) in the synovial tissue of rheumatoid arthritis (RA) exhibit over-proliferative and aggressive phenotypes, which participate in the pathophysiology of RA. In RA, little is known about the non-antioxidant effect of nuclear factor erythroid 2-related factor 2 (nrf2), master regulator of redox homeostasis. In this study, we explored the expression and upstream regulatory factors of nrf2, and revealed its functions in modulating the proliferation and invasion in RA-FLS.
Methods.

FLS were isolated from RA and osteoarthritis patients. Expression of nrf2 in the synovial tissues and FLS was analyzed by immunohistochemistry, real-time PCR, western blot, and immunofluorescence. Cell proliferation was examined by Cell Counting Kit-8, and cell invasion was tested by transwell assay. Phosphorylation of JNK was determined by Western blot.
Results.

Nrf2 expression in the RA synovial tissues was upregulated. TNF-α promoted expression and nuclear translocation of nrf2 in RA-FLS, and increased the intracellular reactive oxygen species (ROS) level. Nrf2 nuclear translocation was blocked by ROS inhibitor N-acetylcysteine. Both knockdown of nrf2 by siRNA and inhibition of nrf2 by ML385 significantly promoted the TNF-α-induced proliferation and invasion of RA-FLS. Activation of nrf2 by sulforaphane (SFN) profoundly inhibited the TNF-α-induced proliferation and invasion of RA-FLS. Knockdown of nrf2 also enhanced the TNF-α-induced matrix metalloproteinases (MMPs) expression and phosphorylation of JNK in RA-FLS. Proliferation and invasion of RA-FLS incubated with TNF-α and nrf2 siRNA was inhibited by pre-treatment with JNK inhibitor SP600125.
Conclusion.

Taken together, nrf2 is over-expressed in synovial tissues of RA patients, which may be induced by TNF-α and ROS levels. Increased nrf2 may suppress TNF-α-induced proliferation, invasion, and MMPs expression in RA-FLS through inhibiting JNK activation, indicating that nrf2 plays a protective role to relieve the severity of synovitis in RA.
Seeking Safety: A Focus Group Study of Young Adults’ Cannabis-Related Attitudes, and Behavior in A State With Legalized Recreational Cannabis
Authors: Amroussia Nada , Watanabe Mika , Pearson Jennifer L
Published: August 2020

Background Only July 1, 2017, Nevada became the fifth state to allow the legal sale of recreational cannabis products for adults over the age of 21 years. This study investigates young adults’ cannabis-related attitudes, perceptions, and behaviors in a state where recreational and medical cannabis use was recently legalized.Methods We conducted 8 focus groups stratified by cannabis use (regular users, occasional users, and nonusers) with 32 college students aged 18 to 24. Data were analyzed using the inductive qualitative thematic analysis method. Results Four themes emerged during analyses: “sort of legal,” “mitigating harm through legalization,” “cannabis use… less risky and more accepted,” and “seeking safety.” Despite their limited knowledge of cannabis regulation, the majority of the participants supported recreational cannabis legalization from a harm reduction perspective. Most participants did not believe that cannabis legalization had affected their use behavior. However, participants, especially cannabis users, perceived that recreational cannabis legalization created a context where cannabis use was legally, socially, and behaviorally “safer” than in an illegal context, even for those below the legal age of use. Conclusions Most studies focus on the role of perceived health risk on cannabis use. If there are population-level long-term effects of recreational cannabis legalization on use behavior, findings suggest that they will be mediated by the perceived legal, social, and behavioral risk of using cannabis.
Is oxygen therapy beneficial for normoxemic patients with acute heart failure? A propensity score matched study
Authors: Yu Yue , Yao Ren-qi , Zhang Yu-feng , Wang Su-yu , Xi Wang , Wang Jun-nan , Huang Xiao-yi , Yao Yong-ming , Wang Zhinong
Published: August 2020

Background The clinical efficiency of routine oxygen therapy is uncertain in patients with acute heart failure (AHF) who do not have hypoxemia. The aim of this study was to investigate the association between oxygen therapy and clinical outcomes in normoxemic patients hospitalized with AHF using real-world data.Methods Normoxemic patients diagnosed with AHF on ICU admission from the electronic ICU (eICU) Collaborative Research Database were included in the current study, in which the study population was divided into the oxygen therapy group and the ambient-air group. Propensity score matching (PSM) was applied to create a balanced covariate distribution between patients receiving supplemental oxygen and those exposed to ambient air. Linear regression and logistic regression models were performed to assess the associations between oxygen therapy and length of stay (LOS), and all-cause in-hospital as well as ICU mortality rates, respectively. A series of sensitivity and subgroup analyses were conducted to further validate the robustness of our findings.Results A total of 2,922 normoxemic patients with AHF were finally included in the analysis. Overall, 42.1% (1,230/2,922) patients were exposed to oxygen therapy, and 57.9% (1,692/2,922) patients did not receive oxygen therapy (defined as the ambient-air group). After PSM analysis, 1,122 pairs of patients were matched: each patient receiving oxygen therapy was matched with a patient without receiving supplemental oxygen. The multivariable logistic model showed that there was no significant interaction between the ambient air and oxygen group for all-cause in-hospital mortality (odds ratio [OR] 1.30; 95% confidence interval [CI] 0.92–1.82; P=0.138) or ICU mortality (OR 1.39; 95% CI 0.83–2.32; P༝0.206) in the post-PSM cohorts. In addition, linear regression analysis revealed that oxygen therapy was associated with prolonged ICU LOS (OR 1.11; 95% CI 1.06–1.15; P༜0.001) and hospital LOS (OR 1.06; 95% CI 1.01–1.10; P༝0.009) after PSM. Furthermore, the absence of an effect of supplemental oxygen on mortality was consistent in all subgroups.Conclusions Routine use of supplemental oxygen in AHF patients without hypoxemia was not found to reduce all-cause in-hospital mortality or ICU mortality.
Knowledge, Attitude and Practice of Health Care Workers on Measuring Adult Vitamin D Level, Diagnosis of Deficiency, and Management of Consequent Health Conditions in Three Ecologies of Ethiopia: A Cross-Sectional Study
Authors: Mekonnen Wubegzier , Feleke Yeweyenhareg , Desalegn Yakob , Tarekegne Getahun , Lambisso Biruk , Haidar Jemal , Zewede Tewabech
Published: August 2020

Background: Vitamin D is very essential for health and its insufficiency is strongly associated with increased overall mortality. Health care workers (HCWs) need to educate on its uses and possible sources although studies show that their knowledge, attitude and practice is low; few studies are available in Ethiopia. The main aim of this study is therefore to assess the knowledge, attitude and practice of measuring adult vitamin D status, diagnosis of deficiency and managing health consequences among HCWs in Ethiopia. Methods: This study was conducted in three districts covering lowland, midland and highland ecologies. A total of 405 health extension workers, nurses, health officers, general practitioners and specialists were interviewed. Tablets were used for data collection to archive in a cloud server. Data were exported to Stata version 14 software for cleaning and analysis. Rates were computed and Chi-square test was used to compare differences between the two groups. Binary logistic regression was used to measure the strength, direction and significance of association between different covariates and the practice of HCWs.Result: The level of good knowledge, positive attitude and good practice in measuring adult vitamin D status, diagnosis of deficiency and managing health consequences among HCWs was 210(51.8%), 261(63.5%) and 195(47.4%) respectively. The odds of good practice in the provision of adult vitamin D service were AOR=6.87: 95% CI (3.57, 13.21) and AOR= 2.20: 95% CI (1.23, 3.92) times higher among HCWs in Addis Ababa and highlands compared with those working in lowlands. Good practice among clinicians was AOR=4.26: 95% CI (1.48, 12.25) times higher compared with those working in leadership positions. The likelihood was AOR=1.96: 95% CI (1.19, 3.23) times higher among those with good knowledge compared with those with poor knowledge. Besides, good practice in adult vitamin D service provision was AOR=2.30: 95% CI (1.40, 3.78) times higher among those with positive attitude compared with those who had negative attitude.Conclusions: Only a little over half of HCWs have good knowledge and close to two-third of them has positive attitude while less than half of them have good practice of measuring adult vitamin D status, diagnosis and managing its health consequences practice. Besides, HCWs residential ecology, clinical position, good knowledge and positive associated is associated with good practice on adult vitamin D. It is essential to provide rigorous and continues training for HCWs focusing on their deployment ecology.
The Effect of Psychosocial Work Environment on the Health-Related Quality of Life of Health Care Providers
Authors: Alshahrani Bashayer , Alumran Arwa
Published: August 2020

Background: Psychosocial work environment is a significant factor in the provision of quality health care. Understanding the psychosocial work environment in the Saudi Arabian health care system is critical in opening up new paths for future workplace interventions and the promotion of quality health care practices. We determined the relationship between psychosocial work environment and quality of life of employees in a major Saudi health care setting. Methods: We designed a quantitative cross-sectional study conducted at King Fahad University Hospital using a Web-based, validated survey targeting all hospital employees. Results: The study results showed that males have significantly higher quality of life and psychosocial work environment scores (t = -2.992, p < .001) than females (t = -2.07, p < 0.05). Employees with day shifts only had significantly higher quality of life scores compared to regular rotation shifts (t = 3.228, p < 0.001). Pearson correlation showed a significant association between quality of life and psychosocial work environment (r = .349, p < .001). The multivariable regression model showed a significant effect of psychosocial work environment, gender, and type of shift on quality of life (adjusted r2 = 0.2665, f = 16.26, p < 0.001). Conclusion: We anticipated that with higher quality of life, employees’ productivity increases. Thus, we expected patient care to improve by increasing health care providers’ quality of life scores. This study showed a significant correlation between psychosocial work environment and quality of life.