bluuebunny/crossref_metadata_2025 huggingface dataset:
‘I’ve got to be independent’: Views of older people on recovery following road traffic injury in New South Wales, Australia
Authors: Brown Katherine , Cameron Ian D , Keay Lisa , Nguyen Ha , Dillon Lisa , Jagnoor Jagnoor , Ivers Rebecca
Published: August 2020

Background: Mild to moderate road traffic injury (RTI) in people of working age is associated with limited recovery. Less is known about RTI recovery in older age. This study explored the perspectives and factors associated with recovery and health-related quality of life following mild to moderate RTI in older age in New South Wales, Australia.Methods: A qualitative study using content analysis was undertaken. Participants aged 65 or more years were purposively selected from a larger inception cohort study of health outcomes following mild to moderate RTI conducted in New South Wales, Australia. Semi-structured interviews were undertaken at approximately 12 or 24 months after injury. Content analysis was used to code and analyse the data, with methodological rigour obtained by double-coding and discussing findings to reach consensus. Results were reported using the consolidated criteria for reporting qualitative research (COREQ). Results: Nineteen participants were invited to participate in the study of which 12 completed interviews. Data saturation was reached at the twelfth interview. Recovery experiences were diverse. Five main themes were identified: recovery is regaining independence; injury and disability in older age; the burden of non-obvious disability; the importance of support; and positive personal approaches. Key facilitators of recovery were: regaining independence; support from family and friends; and positive personal approaches. Key barriers were: threats to independence; passive coping behaviours; non-obvious disabilities (chronic pain, psychological impacts); and for some, a reluctance to raise ongoing issues with General Practitioners. Threats to independence, especially not driving and self-care, appeared to have a more profound effect on recovery than physical functioning.Conclusion: Older people view injury as a threat to independent functioning. This is somewhat different to what younger people report. Regaining independence is key to older people’s recovery and health-related quality of life following RTI, and should be a key consideration for health professionals, services and supports working with this unique cohort. Greater efforts to help older people regain their independence following RTI are needed and can be facilitated by health professionals and appropriate service provision.
The performance of Cu2+ as dissolved cathodic electron-shuttle mediator for Cr6+ reduction in the microbial fuel cell
Authors: Gangadharan Praveena , Nambi Indumathi M
Published: August 2020

The study investigates the performance of Cu2+ as dissolved cathodic electron-shuttle mediator (dcESM) for simultaneous Cr6+ reduction and electricity generation in a microbial fuel cell (MFC) at pH 2 and 4 conditions. The dcESM behavior of Cu2+ on carbon cloth (CC) catalyzes the reduction of Cr6+ into Cr3+ at pH 2 by undergoing redox reactions. However, at pH 4, a simultaneous reduction of Cu2+ and Cr6+ was observed. Cyclic voltammetry studies were performed at pH 2 and 4 to probe the dcESM behavior of Cu2+ for Cr6+ reduction on CC electrode. Also, at pH 2, increasing the concentration of Cu2+ from 50 to 500 mg L-1 favors the Cr6+ reduction by reducing the reaction time from 108 to 48 h and improving the current production from 3.9 to 6.2 mA m-2, respectively. Nevertheless, at pH 4, the efficacy of Cr6+ reduction and electricity generation from MFC is decreased from 63 to 18% and 4.4 to 1.1 mA m-2, respectively, by increasing the Cu2+ concentration from 50 to 500 mg L-1. Furthermore, the performance of dcESM behavior of Cu2+ was explored on carbon felt (CF) and platinum (Pt) electrodes, and compare the results with CC. In MFC, at pH 2, with an initial concentration of 100 mg L-1, the reduction of Cr6+ in 60 h is 9.6 mg L-1 for CC, 0.2 mg L-1 for CF, and 51.3 mg L-1 for Pt cathodes. The reduction of Cr6+ (initial concentration of 100 mg L-1) at pH 4 in 120 h is 44.7 mg L-1 for CC, 32.1 mg L-1 for CF, and 70.9 mg L-1 for Pt cathodes. Maximum power densities of 1659, 1509, and 1284 mW m-2 were achieved when CF, CC, and Pt, respectively were employed as cathodes in the MFC.
Identification and Characterization of the Bacteriocin Carocin S3 from the Multiple Bacteriocin Producing Strain of Pectobacterium carotovorum subsp. carotovorum
Authors: Wang Jyun-Wei , Derilo Reymund Callanga , Lagitnay Ruchi Briam James , Wu Huang-Pin , Chen Kai-In , Chuang Duen-Yau
Published: August 2020

Background: Pectobacterium carotovorum subsp. carotovorum belongs to the Enterobacteriaceae family which causes soft-rot disease in numerous plants worldwide resulting in significant economic losses.Results from our previous studies showed that the strain H-rif-8-6 produces low-molecular-weight bacteriocin (LMWB) Carocin S1. Interestingly, TH22-10, the caroS1K:Tn5 insertional mutant in H-rif-8-6, loses Carocin S1 producing ability, but still produces other LMWBs which can be detected by using the indicator strain SP33. The SP33 is one of the many strains that are sensitive toward the cytotoxic effects of Carocin S3K, but not Carocin S1. The result revealed that H-rif-8-6 is a multiple-bacteriocin producing strain. Results: In this study, a 4.1-kb DNA fragment was isolated from the chromosomal DNA of Pcc strain, H-rif-8-6, by a DNA probe using the caroS1K gene as the template. DNA sequencing and analysis by GenBank revealed two complete open reading frames (ORFs), designated ORF1 and ORF2, which were identified within the sequence fragment. ORF1 and ORF2, similar to the identified Carocin S2 genes, encode the killer (Carocin S3K) and the immunity (Carocin S3I) proteins, respectively, which were homologous to the colicin E3 gene. Carocin S3K and Carocin S3I were expressed, isolated, and purified in Escherichia coli BL21 after subcloning of the expression plasmid pGS3KI or pGSK3I. SDS-PAGE analysis showed that the relative masses of Carocin S3K and Carocin S3I were 95.6 kDa and 10.2 kDa, respectively. The results reveal that Carocin S3K has higher antimicrobial and specific antimicrobial activities for Pcc along with a nuclease activity than Carocin S3I. However, Carocin S3I inhibits the activity of Carocin S3K. Interestingly, high concentration of Carocin S3I protein is also a DNA nuclease, and its activity is also inhibited by Carocin S3K.Conclusion: This study showed that another type of bacteriocin was found in Pectobacterium carotovorum. This new type of bacteriocin, Carocin S3, has the killer protein, Carocin S3K, and the immunity protein, Carocin S3I.
Prevalence of Non-Communicable Diseases and its Risk Factors among Ijegun-Isheri Osun Residents in Lagos State, Nigeria: A Community Based Cross-Sectional Study
Authors: Idris Israel Oluwaseyidayo , Oguntade Ayodipupo Sikiru , Mensah Ekow Adom , Kitamura Noriko
Published: August 2020

Background: The rapid epidemiologic transition of diseases has adverse implications for low-and middle-income countries (LMICs) like Nigeria due to their limited healthcare, weaker health systems and the westernization of lifestyle. There is a need to evaluate the enormity or otherwise of non-communicable diseases (NCDs) burden in such low resource settings. We performed this survey to determine the prevalence of NCDs and its risk factors among the Ijegun- Isheri Osun community residents of Lagos, Nigeria.Methods: A community-based cross-sectional survey was performed on 215 respondents recruited consecutively during a population preventive health campaign. Prevalence of three NCDs (hypertension, diabetes and dyslipidaemia) were calculated. Associations between each of these NCDs and selected risk factors were determined using chi square test. Multivariable logistic regression was used to estimate the risk factors of each of the three NCDs.Results: The prevalence of hypertension was 35.3% (95%CI 29.0-42.1), diabetes 4.6% (95%CI 2.2-8.4) and dyslipidaemia 47.1% (95%CI 41.1-54.8). Among the NCD risk factors, the prevalence of smoking was 41.3% (95%CI 34.2-48.6), alcohol consumption 72.5% (95% CI 65.5-78.7), and physical activity 52.9 (95%CI 45.5-60.2). The independent significant predictors of hypertension were age ≥60 years (aOR 4.56; 95%CI: 1.72-12.09) and dyslipidaemia (aOR 5.01; 95%CI: 2.26-11.13). Age ≥60 years (aOR 8.83; 95%CI: 1.88-41.55) was an independent predictor of diabetes. Age ≥60 years (aOR 29.32; 95%CI: 4.78-179.84), being employed (aOR 11.12; 95%CI: 3.10-39.92), smoking (aOR 2.34; 95%CI: 1.03-5.33) and physical activity (aOR 0.34; 95%CI: 0.15-0.76) were independent predictors of having dyslipidaemia.Conclusions: The prevalence of hypertension, diabetes and dyslipidaemia and their associated risk factors are high among the respondents of Ijegun-Isheri Osun community of Lagos state, Nigeria. This highlights the need for further implementation research and policy directions to tackle NCD burden in urban communities in Nigeria. These strategies must be community specific, prioritizing the various risk factors and addressing them accordingly.
The rs28757157 and rs59429575 polymorphisms in CYP19A1 are associated with lung cancer in Chinese Han population
Authors: Zhang Chan , Cheng Yujing , Chen Wanlu , Li Qi , Dai Run , Wang Yajie , Yang Tonghua
Published: August 2020

Background: Lung cancer is the leading cause of cancer death globally. Recent studies have revealed that the CYP19A1 gene played a crucial role in cancer initiation and development. The aim of this study was to assess the association of CYP19A1 genetic polymorphisms with the risk of lung cancer in the Chinese Han population.Method: This study randomly recruited 507 lung cancer patients and 505 healthy controls. The genotypes of four SNPs of CYP19A1 gene were identified by Agena MassARRY technique. Genetic model analysis was used to assess the association between genetic variation and lung cancer risk. Odds ratio (OR) values and 95% confidence intervals (CIs) were provided for the evaluation of the lung cancer risk effect.Results: Rs28757157 and rs59429575 polymorphisms of CYP19A1 were significantly correlated with the risk of lung cancer. In stratified analysis, rs28757157 was associated with increased cancer risk in smoker and individuals aged ≤60 years. Meanwhile, rs59429575 was identified as a risk biomarker in female and lung adenocarcinoma patients (p < 0.05). While rs28757157 exerted a protective role among people with a BMI greater than 24 (p = 0.033).Conclusions: This study identified two new SNPs (rs28757157 and rs59429575) of CYP19A1 associated with lung cancer in Chinese Han population. These findings provide data support for further functional studies of CYP19A1 in lung cancer.
Application of compound material alleviates saline and alkaline stress in cotton leaves through regulation of the transcriptome
Authors: An Mengjie , Wang Xiaoli , Chang Doudou , Wang Shuai , Hong Dashuang , Fan Hua , Wang Kaiyong
Published: August 2020

Background: Soil salinization and alkalinization are the main factors that affect the agricultural productivity. Evaluating the persistence of the compound material applied in field soils is an important part of the regulation of the responses of cotton to saline and alkaline stresses.Result: To determine the molecular effects of compound material on the cotton’s responses to saline stress and alkaline stress, cotton was planted in the salinized soil (NaCl 8g kg -1 ) and alkalized soil (Na 2 CO 3 8g kg -1 ) after application of the compound material, and ion content, physiological characteristics, and transcription of new cotton leaves at flowering and boll-forming stage were analyzed. The results showed that compared with saline stress, alkaline stress increased the contents of Na + , K + , SOD, and MDA in leaves. The application of the compound material reduced the content of Na + but increased the K + /Na + ratio , the activities of SOD, POD, and CAT, and REC. Transcriptome analysis revealed that after the application of the compound material, the Na + /H + exchanger gene in cotton leaves was down-regulated, while the K + transporter, K + channel, and POD genes were up-regulated. Besides, the down-regulation of genes related to lignin synthesis in phenylalanine biosynthesis pathway had a close relationship with the ion content and physiological characteristics in leaves. The quantitative analysis with PCR proved the reliability of the results of RNA sequencing.Conclusion: These findings suggest that the compound material alleviated saline stress and alkaline stress on cotton leaves by regulating candidate genes in key biological pathways, which improves our understanding of the molecular mechanism of the compound material regulating the responses of cotton to saline stress and alkaline stress.
Clinical Phenotypes and Heath-Related Quality of Life of COPD Patients in a Rural Setting in Malaysia – A Cross-Sectional Study
Authors: Chai Chee-Shee , Mos Sumastika Bt , Ng Diana-Leh-Ching , Goh Greta-Miranda-Kim-Choo , Su Anselm-Ting , Ibrahim Muhammad Amin Bin , Musa Aisya Natasya Bt , Tan Seng-Beng , Pang Yong-Kek , Liam Chong-Kim
Published: August 2020

Background: The Spanish chronic obstructive pulmonary disease (COPD) guideline phenotypes patients according to the exacerbation frequency and COPD subtypes. In this study, we compared the patients’ health-related quality of life (HRQoL) according to their COPD phenotypes.Methods: This was a cross-sectional study of COPD patients who attended the outpatient clinic of the Serian Divisional Hospital and Bau District Hospital from 23th January 2018 to 22th January 2019. The HRQoL was assessed using modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c). Results: Of 185 patients, 108 (58.4%) were non-exacerbators (NON-AE), 51 (27.6%) were frequent exacerbators (AE), and the remaining 26 (14.1%) had asthma-COPD overlap (ACO). Of AE patients, 42 (82.4%) had chronic bronchitis and only 9 (17.6%) had emphysema. Of the 185 COPD patients, 65.9% had exposure to biomass fuel and 69.1% were ex- or current smokers. The scores of mMRC, CAT, and SGRQ-c were significantly different between COPD phenotypes (p < 0.001). There were significantly more patients with mMRC 2 – 4 among AE (68.6%) (p < 0.001), compared to those with ACO (38.5%) and NON-AE (16.7%). AE patients had significantly higher total CAT (p = 0.003; p < 0.001) and SGRQ-c (both p < 0.001) scores than those with ACO and NON-AE. Patients with ACO had significantly higher total CAT and SGRQ-c (both p < 0.001) scores than those with NON-AE. AE patients had significantly higher score in each item of CAT and component of SGRQ-c compared to those with NON-AE (all p < 0.001), and ACO [(p = 0.003 – 0.016; p = < 0.001 – 0.005) except CAT 1, 2 and 7. ACO patients had significantly higher score in each item of CAT and component of SGRQ-c (p = < 0.001 – 0.040; p < 0.001) except CAT 2 and activity components of SGRQ-c.Conclusions: The HRQoL of COPD patients was significantly different across different COPD phenotypes. HRQoL was worst in AE, followed by ACO and NON-AE. This study supports phenotyping COPD patients based on their exacerbation frequency and COPD subtypes. The treatment of COPD should be personalised according to these two factors.
Identification of a metabolism-related gene expression prognostic model in endometrial carcinoma patients
Authors: Jiang Pinping , Sun Wei , Shen Ningmei , Huang Xiaohao , Fu Shilong
Published: August 2020

Background: Metabolic abnormalities have recently been widely studied in various cancer types. This study aims to explore the expression profiles of metabolism-related genes (MRGs) in endometrial cancer (EC). Methods: We analyzed the expression of MRGs using The Cancer Genome Atlas (TCGA) data to screen differentially expressed MRGs (DE-MRGs) significantly correlated with EC patient prognosis. Functional pathway enrichment analysis of the DE-MRGs was performed. LASSO and Cox regression analyses were performed to select MRGs closely related to EC patient outcomes. A prognostic signature was developed, and the efficacy was validated in part of and the entire TCGA EC cohort. Moreover, we developed a comprehensive nomogram including the risk model and clinical features to predict EC patients' survival probability. Results: Forty-seven DE-MRGs were significantly correlated with EC patient prognosis. Functional enrichment analysis showed that these MRGs were highly enriched in amino acid, glycolysis, and glycerophospholipid metabolism. Nine MRGs were found to be closely related to EC patient outcomes: CYP4F3, CEL, GPAT3, LYPLA2, HNMT, PHGDH, CKM, UCK2 and ACACB. Based on these nine DE-MRGs, we developed a prognostic signature, and its efficacy in part of and the entire TCGA EC cohort was validated. The nine-MRG signature was independent of other clinical features, and could effectively distinguish high- and low-risk EC patients and predict patient OS. The nomogram showed excellent consistency between the predictions and actual survival observations. Conclusions: The MRG prognostic model and the comprehensive nomogram could guide precise outcome prediction and rational therapy selection in clinical practice.
mRNA profile provides novel insights into stress adaptation in mud crab megalopa, Scylla paramamosain after salinity stress
Authors: Zhang Yin , Wu Qingyang , Fang Shaobin , Li Shengkang , Zheng Huaiping , Zhang Yueling , Ikhwanuddin Mhd , Ma Hongyu
Published: August 2020

Background : Mud crab, Scylla paramamosain , a euryhaline crustacean species, mainly inhabits the Indo-Western Pacific region. Wild mud crab spawn in high-salt condition and the salinity reduced with the growth of the hatching larvae. When the larvae grow up to megalopa, they migrate back to estuaries and coasts in virtue of the flood tide, settle and recruit adult habitats and metamorphose into the crablet stage. Adult crab can even survive in a wide salinity of 0-35 ppt. To investigate the mRNA profile after salinity stress, S. paramamosain megalopa were exposed to different salinity seawater (low, 14 ppt; control, 25 ppt; high, 39 ppt). Results : Firstly, from the expression profiles of Na+/K+/2Cl- cotransporter , chloride channel protein 2 , and ABC transporter , it turned out that the 24 h might be the most influenced duration in the short-term stress. We collected megalopa under different salinity for 24 h and then submitted to mRNA profiling. Totally, 57.87 Gb Clean Data were obtained. The comparative genomic analysis detected 342 differentially expressed genes (DEGs). The most significantly DEGs include gamma-butyrobetaine dioxygenase-like , facilitated trehalose transporter Tret1 , sodium/potassium-transporting ATPase subunit alpha , rhodanese 1-like protein , etc. And the significantly enriched pathways were lysine degradation, choline metabolism in cancer, phospholipase D signaling pathway, Fc gamma R-mediated phagocytosis, and sphingolipid signaling pathway. The results indicate that in the short-term salinity stress, the megalopa might regulate some mechanism such as metabolism, immunity responses, osmoregulation to adapt to the alteration of the environment. Conclusions : This study represents the first genome-wide transcriptome analysis of S. paramamosain megalopa for studying its stress adaption mechanisms under different salinity. The results reveal numbers of genes modified by salinity stress and some important pathways, which will provide valuable resources for discovering the molecular basis of salinity stress adaptation of S. paramamosain larvae and further boost the understanding of the potential molecular mechanisms of salinity stress adaptation for crustacean species.
The Inattentiveness of Children with ADHD may Worsen During the COVID-19 Quarantine
Authors: Sasaki Tsuyoshi , Niitsu Tomihisa , Tachibana Masumi , Takahashi Jumpei , Iyo Masaomi
Published: August 2020

Objective: The coronavirus disease 2019 pandemic has caused school closures worldwide. Japan's Prime Minister declared a state of emergency based on the coronavirus pandemic for Tokyo, Chiba, and other prefectures on April 7, 2020. Children with ADHD are particularly vulnerable to the distress caused by the pandemic and physical distancing measures, and they might display increased behavioral problems. We surveyed 15 children with ADHD, aged 11.8 ± 2.8 years old; 13 were males and 2 were females (combined subtype, n=12; inattentive subtype, n=3). The children's ADHD-RS scores were assessed by their mother (n=12), father (n=1), or nursing home staff (n=2) from before the emergency declaration (in February or March 2020) to after the emergency declaration (April or May 2020). There were no changes of treating physician, drug type or quantity, or psychotherapy or assessment person from January 2020 to May 2020. Results: A comparison of the baseline scores and secondary outcomes reveals that the ADHD-RS total score and inattentive subscore worsened significantly during this period, whereas the hyper/impulsive subscore did not. In conclusion, we suggest that policymakers, healthcare providers and families should be mindful of the potential development of inattentiveness among children with ADHD who are quarantined because of COVID-19.
Sialylated Human Milk Oligosaccharides Prevent Intestinal Inflammation by Inhibiting Toll Like Receptor 4-Mediated Inflammatory Events in Necrotizing Enterocolitis Rats and Lipopolysaccharide-Stimulated Human Colonic Epithelial Caco-2 Cells
Authors: Zhang Wenting , Heyang Jingqiu , Tu Wenjuan , Zhou Xiaoying
Published: August 2020

The authors have withdrawn this preprint due to author disagreement.
Characterization of volatile fatty-acid utilization in Escherichia coli aiming for robust valorisation of food residues
Authors: Sjöberg Gustav , Gustavsson Martin , Maris Antonius J.A. van
Published: August 2020

Valorisation of food residues would greatly benefit from development of robust processes that create added value compared to current feed- and biogas applications. Recent advances in membrane-bioreactor-based open mixed microbial cultures, enable robust conversion of fluctuating streams of food residues to a mixture of volatile fatty acids (VFAs). In this study, such a mixed stream of VFAs was investigated as a substrate for Escherichia coli, a well-studied organism suitable for application in further conversion of the acids into compounds of higher value, and/or that are easier to separate from the aqueous medium. E. coli was cultured in batch on a VFA-rich anaerobic digest of food residues, tolerating up to 40 mM of total VFAs without any reduction in growth rate. In carbon-limited chemostats of E. coli W3110 ΔFadR on a simulated VFA mixture, the straight-chain VFAs (C2-C6) in the mixture were readily consumed simultaneously. At a dilution rate of 0.1 h− 1, mainly acetic-, propionic- and caproic acid were consumed, while consumption of all the provided acids were observed at 0.05 h− 1. Interestingly, also the branched isovaleric acid was consumed through a hitherto unknown mechanism. In total, up to 80% of the carbon from the supplied VFAs was consumed by the cells, and approximately 2.7% was excreted as nucleotide precursors in the medium. These results suggest that VFAs derived from food residues are a promising substrate for E. coli.
Survival Benefit of Ixazomib, Lenalidomide and Dexamethasone (IRD) Over Lenalidomide and Dexamethasone (Rd) in Relapsed and Refractory Multiple Myeloma Patients in Routine Clinical Practice
Authors: Minarik Jiri , Pika Tomas , Radocha Jakub , Jungova Alexandra , Straub Jan , Jelinek Tomas , Pour Ludek , Pavlicek Petr , Mistrik Martin , Brozova Lucie , Krhovska Petra , Machalkova Katerina , Jindra Pavel , Spicka Ivan , Plonkova Hana , Stork Martin , Bacovsky Jaroslav , Capkova Lenka , Sykora Michal , Kessler Petr , Stejskal Lukas , Heindorfer Adriana , Ullrychova Jana , Skacel Tomas , Maisnar Vladimir , Hajek Roman
Published: August 2020

Background: We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and refractory multiple myeloma (RRMM) in the routine clinical practice. Methods: A total of 344 patients treated with IRD (N=127) or RD (N=217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient’s characteristics associated with the respective therapy. The primary endpoint was progression free survival (PFS), secondary end points included response rates and overall survival (OS). Survival endpoints were plotted using Kaplan-Meier methodology at 95% Greenwood confidence interval. Univariable Cox proportional hazards models were used to evaluate the effect of treatment regimen. Statistical tests were performed at significance level 0.05.Results: In the whole cohort, PFS for IRD was 17.5 and for RD was 11.5 months favoring the all-oral triplet, p = 0.005; in patients within relapse 1-3, the median PFS was 23.1 vs 11.6 months, p = 0.001. The hazard ratio for PFS was 0.67 (95% confidence interval [CI] 0.51 – 0.89, p = 0.006). The PFS advantage translated into improved OS for patients treated with IRD, median 36.6 months vs 26.0 months (p = 0.008). The overall response rate (ORR) was 73.0 % in the IRD group vs 66.2 % in the RD group with a complete response rate (CR) of 11.1 % vs 8.8 %, and very good partial response (VGPR) 22.2 % vs 13.9 %, IRD vs RD respectively. The IRD regimen was most beneficial in patients ≤75 years with ISS I, II, and in the first and second relapse. Patients with the presence of extramedullary disease did not benefit from IRD treatment (median PFS 6.5 months). Both regimens were well tolerated, and the incidence of total as well as grade 3/4 toxicities was comparable. Conclusions: Our analysis confirms the results of the TOURMALINE-MM1 study and shows benefit of all-oral triplet IRD treatment versus RD doublet. It demonstrates that the addition of ixazomib to RD improves key survival endpoints in patients with RRMM in a routine clinical setting.
Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase
Authors: Siedner Mark , Moorhouse Michelle , Simmons Brioni , de Oliveira Tulio , Lessells Richard , Giandhari Jennifer , Kemp Steven , Chimukangara Ben , Akpomiemie Godspower , Serenata Celicia , Venter Willem , Hill Andrew , Gupta Ravindra
Published: August 2020

Background: Little is known about the impact of pre-treatment drug resistance (PDR) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) on the efficacy of second generation integrase inhibitors, now the standard of care drug class for HIV-1 treatment globally.Methods: We conducted next-generation sequencing on stored plasma specimens from the ADVANCE trial collected prior to treatment initiation. Our primary outcome was 96-week virologic success, defined as achievement of a viral load < 1000 copies/mL from 12 weeks, < 200 copies/mL from 24 weeks, and < 50 copies/mL from 48 through 96 weeks. We estimated the impact of PDR, defined by the presence of drug resistance on the World Health Organization (WHO) mutation list, on virologic outcomes in the entire cohort, and stratified by EFV-based versus DTG-based regimens. In sensitivity analyses, we allowed virologic failure with re-suppression, assessed FDA 48 and 96-week Snapshot outcomes, and considered minority resistance mutations (5–20% frequency).Results: Of 1,053 trial participants, 873 (83%) had plasma available and successful sequencing completed. Of these, 288 (33%) were randomized to an EFV-based regimen and 585 (67%) were randomized to a DTG-based regimen. Fourteen percent (122/873) had at least one WHO-defined mutation, of which over 98% (120/122) had NNRTI mutations. NRTI mutations were rare (20/873, 2%). Rates of virologic suppression were significantly lower in those with PDR 65% (73/112) compared to those without PDR (85% [605/713], P < 0.001). This phenomenon was consistent for both EFV-based (60% [12/20] versus 86% [214/248], P = 0.002) and DTG-based ART (61/92 [66%] versus 84% [391/465] P < 0.001, P for interaction by regimen 0.49). In multivariable models adjusted for clinical characteristics and treatment adherence, PDR strongly predicted failure [adjusted OR 0.38 (0.23–0.61), P < 0.001]. Although suppression rates were greater when allowing for non-consecutive visits with failure, PDR significantly predicted greater risk of failure for both regimens in all outcome definitions. We found no effect of mutations at frequencies 5–20% on any of our outcomes.Interpretation: NNRTI resistance prior to treatment initiation is associated with failure of integrase inhibitor-containing first-line regimens. These results portend high rates of first-line treatment failure in sub Saharan Africa, where circulating NNRTI resistance is common.
Empagliflozin Protects Atherosclerosis Progression by Modulating Lipid Profiles and Sympathetic Activity
Authors: Liu Yihai , Xu Jiamin , Wu Mingyue , Xu Biao , Kang Lina
Published: August 2020

Background: Several large clinical trials have confirmed the cardioprotective role of Sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes. Here we investigated that empagliflozin, as an SGLT2 inhibitor, could alleviate atherosclerosis progression.Methods: ApoE-/- mice were fed on a western diet for 12 weeks to induce atherosclerosis. On the 7th week, a group of mice were treated with drinking water containing empagliflozin (10mg/kg/day) while another group was still fed on normal water. On 12th week, the whole aortas of each group were harvested. The Oil red O, HE and movat staining were performed for atherosclerotic lesion area and size. Mouse serum lipid profiles (TC, TG, LDL-C, and HDL-C), systemic inflammation level (IL-1β, IL-6 and IL-10), renin-angiotensin-aldosterone system (RAAS) and sympathetic activity (norepinephrine, and neuropeptide Y) were measured by ELISA.Results: Empagliflozin reduced the atherosclerotic lesion burden in ApoE-/- mice. Besides, empagliflozin decreased the body weight, lipid profiles, RAAS and sympathetic activity. However, the anti-inflammation effect of empagliflozin was not significantly evident. Conclusions: Empagliflozin can partly prevent atherosclerosis in ApoE-/- mice, which could be attributed to its inhibition on lipid profiles, and sympathetic activity.
Effect of Spinal Alignment Changes on Low Back Pain in Patients Treated with Total Hip Arthroplasty for Hip Osteoarthritis
Authors: Saiki Fumiko , Tanaka Takeyuki , Tachibana Naohiro , Oshima Hirofumi , Kaneko Taizo , Horii Chiaki , Nakamoto Hideki , Kato So , Doi Toru , Matsubayashi Yoshitaka , Taniguchi Yuki , Tanaka Sakae , Oshima Yasushi
Published: August 2020

BackgroundTotal hip arthroplasty (THA) is an established procedure for patients with osteoarthritis (OA) of the hip joint that effectively relieves pain and restores function. Because contracture of the hip joint as well as preoperative leg length discrepancy is expected to improve by the surgery, it would be reasonable to speculate that spinal sagittal alignment will also change. However, the influence of spinal alignment changes on clinical symptoms, such as low back pain (LBP), remains controversial. In this study, we aimed to evaluate the associations between spinal alignment changes and improvement in preoperative LBP after THA.MethodsFrom November 2015 to January 2017, 104 consecutive patients who underwent THA were prospectively enrolled. Whole spine X-rays were obtained preoperatively and 12 months postoperatively. The patient-reported outcomes (PROs) used were the Numerical Rating Scale (NRS) for back pain, EuroQol 5 Dimension, and Short Form-12. The presence of LBP was defined as an NRS of ≥4. Changes in spinal alignment and PROs before and after surgery were evaluated.ResultsSeventy-four (71%) patients were included in the study. The sagittal spinal parameters changed slightly but significantly; pelvic incidence (PI) decreased, pelvic tilt (PT) increased, and sacral slope decreased. Coronal spinal alignment significantly improved after surgery. Twenty-six (37%) patients had LBP preoperatively. The patients with preoperative LBP had smaller lumbar lordosis (LL), larger PT, and larger PI minus LL than those in the patients without. Fourteen (54%) of the 26 patients with preoperative LBP showed improvement, but there were no significant differences in the pre- and postoperative radiographic parameters.ConclusionAlthough preoperative LBP was likely to resolve after THR, there were no significant correlations between alignment changes and LBP improvement. The cause of LBP in patients with hip OA patients might be multifactorial.
COVID-19 and Guillain-Barre Syndrome - a Case report
Authors: Sidig Amira , Abbasher Khabab , Digna Mutaz F. , Elsayed Mohamed , Abbasher Hussien , Abbasher Mohammed , Hussien Abbasher
Published: August 2020

Coronaviruses are a family of related viruses that cause diseases in mammals and avians. Guillain-Barre syndrome is a rare disorder in which the body's immune system attacks peripheral nerves.The case:A 65 years old Sudanese male with no diabetes mellitus or hypertension present to the clinic; On examination, he has upper and lower limb weakness (quadriplegia). The condition was preceded by upper respiratory tract infection. Chest X-ray showed features of pneumonia Chest CT scan showed multiple bilateral ground-glass opacities and consolidation typical of COVID-19 pneumonia. Brain MRI was normal. The COVID-19 nasal swab test was positive. Nerve conduction study showed evidence of polyradiculopathies with dominant demyelination supporting the diagnosis of Guillain-Barre syndrome. The patients died after seven days; because of progressive respiratory failure.
Muscles Adaptation to Aging and Training: Architectural Changes – A Randomised Trial
Authors: LÉTOCART Adrien J. , Mabesoone Franck , Charleux Fabrice , Couppé Christian , Svensson Rene B. , Marin Frédéric , Magnusson S. Peter , Grosset Jean-François
Published: August 2020

Background: To investigate how anatomical cross-sectional area and volume of quadriceps and triceps surae muscles were affected by ageing, and by resistance training in older and younger men, in vivo. Methods: The old participants were randomly assigned to moderate (O55, n=13) or high-load (O80, n=14) training intervention (12 weeks; 3 times/week) corresponding to 55% or 80% of one repetition maximum, respectively. Young men (Y55, n=11) were assigned to the moderate-load training program. Each groups received the exact same training volume on triceps surae and quadriceps group (Reps x Sets x Intensity). The fitting polynomial regression equations for each of anatomical cross-sectional area-muscle length curves were used to calculate muscle volume (contractile content) before and after 12 weeks using magnetic resonance imaging scans.Results: Only Rectus femoris and medial gastrocnemius muscle showed a higher relative anatomical cross-sectional area in the young than the elderly on the proximal end. The old group displayed a higher absolute volume of non-contractile material than young men in triceps surae (+96%). After training, Y55, O55 and O80 showed an increase in total quadriceps (+4.3%; +6.7%; 4.2% respectively) and triceps surae (+2.8%; +7.5%; 4.3% respectively) volume. O55 demonstrated a greater increase on average gains compared to Y55, while no difference between O55 and O80 was observed.Conclusions: Muscle loss with aging is region-specific for some muscles and uniform for others. Equivalent training volume at moderate or high intensities induced no additional muscle volume gains for old men. These data suggest that physical exercise at moderate intensity (55 to 60% of one repetition maximum) can retain the aging related loss of muscle mass.Trial registration: CPP-2016/52 (France) and on Clinical Trials.gov (2016-A00534-47)
Fatal Sickling Associated Microvascular Occlusive Crisis in a Young Military Recruit with Sickle Cell Trait: A Case Report
Authors: Mutreja Deepti , K Benjith Paul , K Tilak T V S V G , Tewari Vanmalini
Published: August 2020

Background.

Sickle cell trait(SCT), a heterozygous state characterized by the presence of hemoglobin AS, occurs in varied frequency in the Indian population with highest prevalence in Central and southern India. SCT is compatible with a normal lifespan and not commonly regarded as a cause of morbid illness or death in contrast to sickle cell disease, its homozygous counterpart.
Case Presentation.

We describe a case of fatal sickling associated microvascular crisis, identified on post mortem evaluation in a previously undiagnosed 20-year-old military recruit with sickle cell trait. The individual presented with repeated episodes of presyncope during his training and was evaluated for cardiac anomalies and heat syncope. During the terminal episode, he collapsed and died of severe metabolic complications as he struggled to complete an organised run during routine training activities.
Conclusion.

To our knowledge, this is the first report of fatal sickling associated crisis in a military recruit with sickle cell trait from India. This case serves to remind all medical officers of the armed forces of the importance of screening a recruit who is unable to complete exertional physical training for the presence of sickle cell trait.
Predictive performance of PiCCO system and blood gas parameters for early prognosis of patients with sepsis
Authors: YUAN JING , Qin XueMei , Wang Tao , Wang Tong , Wu Jinyi , Shen Guanggui , Cao Yinya , Lu Weihua , Wang Zhen
Published: August 2020

Purpose: Invasive hemodynamics monitor directed fluids resuscitation remains misgiving issues. This study aims to explore the predictive value of the PiCCO system (pulse indicator continuous cardiac output device) and blood gas parameters on the early prognosis of patients with sepsis.Methods: 42 patients with sepsis were included from January 2013 to January 2015. All patients were stratified into survivor group (n=29) and nonsurvivor group (n=13) based on seven day-mortality. The PiCCO and blood gas parameters at enrollment and 24 hours were compared between two groups. The predictive performance of these parameters was distinguished with Area Under the Receiver Operating Characteristic Curve (AUC). Results: At 24 hours after enrollment, the HR (97.27±22.07 vs. 120.20±20.56), extravascular lung water index (EVLWI) (7.32±2.96 vs. 15.9±11.2), and lactic acid (Lac) (1.62±0.92 vs. 6.33±5.83) level were significantly lower in survivor group (P < 0.05), whereas the cardiac index (CI) (3.67±0.85 vs. 2.98±0.73) and PaO2/FiO2 (242.8±89.68 vs.136.07±78.01) increased significantly. Meanwhile PaO2/FiO2 was negatively correlated with EVLWI (r= -0.673, P < 0.01). The AUC of the combination of Lac with PaO2/FiO2, HR, EVLWI, pulmonary vascular permeability index (PVPI) and Lac at 24 hours were 0.853, 0.739, 0.776, 0.764, and 0.794.Conclusions: The PiCCO and blood gas parameters exhibit superior predictive capability for early prognosis in patients with sepsis, and the combination Lac with PaO2/FiO2 was noninferior under the circumstance of unavailability with PiCCO.
Spontaneous Pneumothorax as Unusual Presenting Symptom of Covid-19 Pneumonia: Surgical Management and Pathological Findings
Authors: Bellini Roberto , SALANDINI MARIA CHIARA , Cuttin Serena , Mauro Stefania , Scarpazza Paolo , Cotsoglou Christian
Published: August 2020

Spontaneous pneumothorax has been reported as a possibile complication of novel coronavirus associated pneumonia (COVID-19). We report two cases of COVID-19 patients who developed spontaeous and recurrent pneumothorax as a presenting symptom, treated with surgical procedure. Intraoperative findings of COVID-19 pneumonia were parenchymal atelectasis and vascular congestion. Lung tissue was very frail and prone to bleeding. Histological examination showed interstitial infiltration of lymphocytes and plasma cells, as seen in non specific interstitial pneumonia, together with myo-intimal thicknening of vessels with blood extravasation and microthrombi. Lung surgery for pneumothorax in COVID-19 patients can be safely and effectively performed when necessary.
Understanding the Causes of Errors in Eukaryotic Protein-coding Gene Prediction: A Case Study of Primate Proteomes
Authors: Meyer Corentin , Scalzitti Nicolas , Jeannin-Girardon Anne , Collet Pierre , Poch Olivier , Thompson Julie
Published: August 2020

Background. Recent advances in sequencing technologies have led to an explosion in the number of genomes available, but accurate genome annotation remains a major challenge. The prediction of protein-coding genes in eukaryotic genomes is especially problematic, due to their complex exon-intron structures. Even the best eukaryotic gene prediction algorithms can make serious errors that will significantly affect subsequent analyses. Results. We first investigated the prevalence of gene prediction errors in a large set of 176,478 proteins from ten primate proteomes available in public databases. Using the well-studied human proteins as a reference, a total of 82,305 potential errors were detected, including 44,001 deletions, 27,289 insertions and 11,015 mismatched segments where part of the correct protein sequence is replaced with an alternative erroneous sequence. We then focused on the mismatched sequence errors that cause particular problems for downstream applications. A detailed characterization allowed us to identify the potential causes for the gene misprediction in approximately half (5446) of these cases. As a proof-of-concept, we also developed a simple method which allowed us to propose improved sequences for 603 primate proteins. Conclusions. Gene prediction errors in primate proteomes affect up to 50% of the sequences. Major causes of errors include undetermined genome regions, genome sequencing or assembly issues, and limitations in the models used to represent gene exon-intron structures. Nevertheless, existing genome sequences can still be exploited to improve protein sequence quality. Perspectives of the work include the characterization of other types of gene prediction errors, as well as the development of a more comprehensive algorithm for protein sequence error correction.
Metagenomic survey and whole genome sequencing of antimicrobial resistant bacteria in the sewage of a Japanese hospital
Authors: Katagiri Miwa , Kuroda Makoto , Sekizuka Tsuyoshi , Nakada Norihide , Ito Yukitaka , Otsuka Masanobu , Watanabe Manabu , Kusachi Shinya
Published: August 2020

Background The dissemination of antimicrobial-resistant bacteria (ARB) and the transfer of antimicrobial resistance genes (ARGs) are a threat to public health. Antibiotics are indispensable therapeutic agents essential for the treatment of infectious diseases; however, inappropriate use of antibiotics leads to the emergence of ARB. It is established that hospitals are closely involved in the spread of antimicrobial resistance (AMR), which impedes antibiotic treatment and subsequently increases mortality. In addition, excrement of patients or healthy carriers of ARB are discharged from the hospital sewage through the wastewater treatment plant (WWTP) into the rivers, causing an AMR burden on the environment.Method Metagenomic analysis was performed on the hospital sewage samples, followed by whole genome sequencing of the extended spectrum β-lactamase (ESBL)-producing organisms (EPOs). A comparative genome analysis was also performed between EPO isolates from sewage and clinical isolates.Results Metagenomic analysis showed that the hospital sewage tanks had bacterial flora corresponding to the human gut. During the study period, the hospital was relocated to a newly constructed building with new sewage tanks; however, the presence of ARB/ARGs in the new hospital sewage tanks became markedly equivalent to that of the old hospital within one month. The ESBL blaCTX−M and carbapenemase blaIMP genes were not much detected in the original hospital sewage samples by metagenome analysis, but selection on CHROMagar ESBL increased the sensitivity to detect those β-lactamase genes. Comparative genome analysis between sewage and clinical EPO isolates revealed partial similarity; however, most EPO isolates exhibited a notable difference (≥ 50) in single nucleotide variations based on core-genome phylogeny. This result suggests that only some of the sewage EPO isolates were originated from the clinical patient. Therapeutic agents in the hospital sewage were analyzed and the concentration of levofloxacin and clarithromycin was 0.0325 and 0.0135 µg/mL, respectively.Conclusions Whole genome analysis between sewage and clinical isolates suggested that healthy or asymptomatic carriers may be involved in the contamination of hospital sewage. Moreover, the hospital sewage tank may serve as a hotspot for the horizontal transfer of ARGs under the selective pressure of antimicrobial agents. Therefore, ARB monitoring in hospital sewage is expected to detect the presence of carriers prior to nosocomial ARB outbreaks. In addition, hospital wastewater should be treated suitably to bring ARB below detectable levels to reduce the environmental AMR burden.
Identification of mammalian-adapting mutations involved into antigenic change of H1N1 influenza virus
Authors: Yu Zhijun , Cheng Kaihui , Sun Weiyang , Zhang Xinghai , Wang Tiecheng , Zhao Yongkun , Wu Jiaqiang , Gao Yuwei , Xia Xianzhu
Published: August 2020

Though the 2009 pandemic H1N1 virus has become a seasonal influenza A virus, continued host adaptation and antigenic drift may limit the effectiveness of current vaccines. Here, we assess viral antigenic change of a 2009 pandemic H1N1 virus (A/Changchun/01/2009) in the absence and presence of immune-mediated selective pressures and further identify the key amino acid substitutions involved into the antigenic change of the 2009 pandemic H1N1 virus. We found that serial passage of the 2009 pandemic H1N1 virus in both naïve and previously immunized mice generated antigenically distinct variants and that serial passage in previously immunized mice generated viruses with lower overall antigenic relatedness to the parental virus when compared to variants generated by serial passage in naïve mice, suggesting that antibody pressure may accelerate the antigenic variation rate of the 2009 pandemic H1N1 virus. Furthermore, we found that three amino acid substitutions in the viral HA protein (N159D, S186P, and D225G), both alone and in combination, affected viral antigenicity. It is noted that all three mutations (N159D, S186P, and D225G) in the viral HA protein have been found in the natural 2009 pandemic H1N1 virus isolates and can also enhance the pathogenicity of the 2009 pandemic H1N1 virus to mammals, suggesting that these mutations in the viral HA protein may pose a potential threat to public health and should be paid more attention. Taken together, our work defines some novel molecular determinants of the pandemic H1N1 virus antigenicity and has important implications for ongoing human influenza virus surveillance efforts.