bluuebunny/crossref_metadata_2025 huggingface dataset:
Ingested toothpick retrieved through a lumbar approach: a case report
Authors: Ling Chun-Run , Chen Yi , He Chun-Gang
Published: May 2020

Background

Ingested toothpick may cause severe complications if there is no intervention timely. Toothpicks that required surgical intervention often retrieved through exploratory laparotomy or laparoscopic exploration surgery under general anesthesia, while, those through lumbar approach have been rarely reported. Herein, authors report a case of ingested toothpick which removed through the lumbar surgical approach under local anesthesia and the patient has gained a considerable recovery.

Case presentation

A 57-year-old man was admitted to our hospital with distending pain in the right flank for more than 20 days. He had a history of accidental toothpick ingestion. Abdominal computed tomography (CT) scan and Color Doppler Ultrasound of the superficial tissue (right flank pain area) consistently revealed a linear lesion -corresponding to the toothpick- was located at the right flank next to the body surface. Surgery via lumbar approach was then successfully performed to retrieve the toothpick under local anesthesia. The post-procedural course was uneventful, and the patient was discharged on the third day after surgery, no complications were noted at the 18-month follow-up.

Conclusion

When a foreign body that causes perforation of the digestive tract remains for a relative long time (non-acute stage) and the perforation is close to the body surface, a local anesthesia surgery through the corresponding body surface may be a considerable choice.
Screening of five marine-derived fungal strains for their potential to produce oxidases with laccase activities suitable for biotechnological applications
Authors: Ben Ali Wissal , Chaduli Delphine , Navarro David , Lechat Christian , Turbé-Doan Annick , Bertrand Emmanuel , Faulds Craig B. , Sciara Giuliano , Lesage-Meessen Laurence , Record Eric , Mechichi Tahar
Published: May 2020

Background

Environmental pollution is one of the major problems that the world is facing today. Several approaches have been taken, from physical and chemical methods to biotechnological strategies (e.g. the use of oxidoreductases). Oxidative enzymes from microorganisms offer eco-friendly, cost–effective processes amenable to biotechnological applications, such as in industrial dye decolorization. The aim of this study was to screen marine-derived fungal strains isolated from three coastal areas in Tunisia to identify laccase-like activities, and to produce and characterize active cell-free supernatants of interest for dye decolorization.

Results

Following the screening of 20 fungal strains isolated from the harbors of Sfax and Monastir (Tunisia), five strains were identified that displayed laccase-like activities. Molecular-based taxonomic approaches identified these strains as belonging to the species Trichoderma asperellum, Stemphylium lucomagnoense and Aspergillus nidulans. Among these five isolates, one T. asperellum strain (T. asperellum 1) gave the highest level of secreted oxidative activities, and so was chosen for further studies. Optimization of the growth medium for liquid cultures was first undertaken to improve the level of laccase-like activity in culture supernatants. Finally, the culture supernatant of T. asperellum 1 decolorized different synthetic dyes belonging to diverse dye families, in the presence or absence of 1-hydroxybenzotriazole (HBT) as a mediator.

Conclusions

The optimal growth conditions to produce laccase-like active cell-free supernatants from T. asperellum 1 were 1.8 mM CuSO4 as an inducer, 1% NaCl to mimic a seawater environment and 3% sucrose as a carbon source. The culture supernatant of T. asperellum 1 effectively decolorized different synthetic dyes belonging to diverse chemical classes, and the presence of HBT as a mediator improved the decolorization process.
Generation of transgene-free PDS mutants in potato by Agrobacterium-mediated transformation
Authors: Bánfalvi Zsófia , Csákvári Edina , Villányi Vanda , Kondrák Mihály
Published: May 2020

Background

Gene editing using the CRISPR/Cas9 system has become a routinely applied method in several plant species. The most convenient gene delivery system is Agrobacterium-mediated gene transfer with antibiotic selection and stable genomic integration of transgenes, including Cas9. For elimination of transgenes in the segregating progeny, selfing is applied in many plant species. This approach, however, cannot be widely employed in potato because most of the commercial potato cultivars are self-incompatible.

Results

In this study, the efficiency of a transient Cas9 expression system with positive/negative selection based on codA-nptII fusion was tested. The PHYTOENE DESATURASE (PDS) gene involved in carotenoid biosynthesis was targeted. A new vector designated PROGED::gPDS carrying only the right border of T-DNA was constructed. Using only the positive selection function of PROGED::gPDS and the restriction enzyme site loss method in PCR of genomic DNA after digestion with the appropriate restriction enzyme, it was demonstrated that the new vector is as efficient in gene editing as a traditional binary vector with right- and left-border sequences. Nevertheless, 2 weeks of positive selection followed by negative selection did not result in the isolation of PDS mutants. In contrast, we found that with 3-day positive selection, PDS mutants appear in the regenerating population with a minimum frequency of 2–10%. Interestingly, while large deletions (> 100 bp) were generated by continuous positive selection, the 3-day selection resulted in deletions and substitutions of only a few bp. Two albinos and three chimaeras with white and green leaf areas were found among the PDS mutants, while all the other PDS mutant plants were green. Based on DNA sequence analysis some of the green plants were also chimaeras. Upon vegetative propagation from stem segments in vitro, the phenotype of the plants obtained even by positive selection did not change, suggesting that the expression of Cas9 and gPDS is silenced or that the DNA repair system is highly active during the vegetative growth phase in potato.

Conclusions

Gene-edited plants can be obtained from potatoes by Agrobacterium-mediated transformation with 3-day antibiotic selection with a frequency high enough to identify the mutants in the regenerating plant population using PCR.
Effect of a postpartum family planning intervention on postpartum intrauterine device counseling and choice: evidence from a cluster-randomized trial in Tanzania
Authors: Pearson Erin , Senderowicz Leigh , Pradhan Elina , Francis Joel , Muganyizi Projestine , Shah Iqbal , Canning David , Karra Mahesh , Ulenga Nzovu , Bärnighausen Till
Published: May 2020

Background

The World Health Organization recommends postpartum family planning (PPFP) for healthy birth spacing. This study is an evaluation of an intervention that sought to improve women’s access to PPFP in Tanzania. The intervention included counseling on PPFP during antenatal and delivery care and introducing postpartum intrauterine device (PPIUD) insertion as an integrated part of delivery services for women electing PPIUD in the immediate postpartum period.

Methods

This cluster-randomized controlled trial recruited 15,264 postpartum Tanzanian women aged 18 or older who delivered in one of five study hospitals between January and September 2016. We present the effectiveness of the intervention using a difference-in-differences approach to compare outcomes, receipt of PPIUD counseling and choice of PPIUD after delivery, between the pre- and post-intervention period in the treatment and control group. We also present an intervention adherence-adjusted analysis using an instrumental variables estimation.

Results

We estimate linear probability models to obtain effect sizes in percentage points (pp). The intervention increased PPIUD counseling by 19.8 pp (95% CI: 9.1 – 22.6 pp) and choice of PPIUD by 6.3 pp (95% CI: 2.3 – 8.0 pp). The adherence-adjusted estimates demonstrate that if all women had been counseled, we would have observed a 31.6 pp increase in choice of PPIUD (95% CI: 24.3 – 35.8 pp). Among women counseled, determinants of choosing PPIUD included receiving an informational leaflet during counseling and being counseled after admission for delivery services.

Conclusions

The intervention modestly increased the rate of PPIUD counseling and choice of PPIUD, primarily due to low coverage of PPIUD counseling among women delivering in study facilities. With universal PPIUD counseling, large increases in choice of PPIUD would have been observed. Giving women informational materials on PPIUD and counseling after admission for delivery are likely to increase the proportion of women choosing PPIUD.

Trial registration

Registered with clinicaltrials.gov (NCT02718222) on March 24, 2016, retrospectively registered.
Evaluation of neuroprotective and anti-amnesic effects of Elaeagnus umbellata Thunb. On scopolamine-induced memory impairment in mice
Authors: Nazir Nausheen , Zahoor Muhammad , Nisar Mohammad , Karim Nasiara , Latif Abdul , Ahmad Sajjad , Uddin Zia
Published: May 2020

Background

Elaeagnus umbellata is abundantly found in Himalayan regions of Pakistan which is traditionally used to treat various health disorders. However, the experimental evidence supporting the anti-amnesic effect is limited. Therefore the study was aimed to evaluate the prospective beneficial effect of E. umbellata on learning and memory in mice.

Objectives

To assess neuroprotective and anti-amnesic effects of E. umbellata fruit extracts and isolated compounds on the central nervous system.

Methods

Major phytochemical groups present in methanolic extract of E. umbellata were qualitatively determined. The total phenolic and flavonoid contents were also determined in extract/fractions of E. umbellata. On the basis of in vitro promising anticholinesterases (AChE & BChE) and antioxidant activities observed for CHF. Ext and isolated compound-I (Chlorogenic acid = CGA), they were further evaluated for learning and memory in normal and scopolamine-induced cognitive impairment in mice using memory behavioral tests such as the Y maze and Novel object recognition using standard procedures. The test sample were further assessed for in vivo anticholinesterases (AChE & BChE) and DPPH free radical scavenging activities in mice brain sample and finally validated by molecular docking study using GOLD software.

Results

The extract/fractions and isolated compounds were tested for their anticholinesterase and antioxidant potentials. The CHF. Ext and CGA showed maximum % inhibition of tested cholinesterases and free radicals. The CHF. Ext and CGA reversed the effects of scopolamine in mice. The CHF. Ext and CGA significantly increased the alternate arm returns and % spontaneous alteration performance while escape latency times (second) significantly decreased in Y maze test. The CHF. Ext and CGA significantly increased the time spent with novel object and also increased the discrimination index in the Novel object recognition test. Furthermore, molecular docking was used to validate the mechanism of cholinesterases inhibition of isolated compounds.

Conclusion

The data obtained from behavioral and biochemical studies (AChE/BChE and DPPH/ABTS inhibition) have shown that E. umbellata possessed significant memory enhancing potency. These results suggest that E. umbellata extract possess potential antiamnesic effects and amongst the isolated compounds, compound I could be more effective anti-amnesic therapeutics. However, further studies are needed to identify the exact mechanism of action.

Graphical abstract
How do 66 European institutional review boards approve one protocol for an international prospective observational study on traumatic brain injury? Experiences from the CENTER-TBI study
Authors:   The CENTER-TBI investigators and participants, Timmers Marjolein , van Dijck Jeroen T. J. M. , van Wijk Roel P. J. , Legrand Valerie , van Veen Ernest , Maas Andrew I. R. , Menon David K. , Citerio Giuseppe , Stocchetti Nino , Kompanje Erwin J. O.
Published: May 2020

Background

The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency.

Methods

We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe.

Results

From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally (N = 11, 61%) or locally (N = 7, 39%) and primary IRB approval was obtained after one (N = 8, 44%), two (N = 6, 33%) or three (N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75–224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074).

Conclusion

We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries.
Actigraphy in brain-injured patients – A valid measurement for assessing circadian rhythms?
Authors: Angerer Monika , Schabus Manuel , Raml Marion , Pichler Gerald , Kunz Alexander B. , Scarpatetti Monika , Trinka Eugen , Blume Christine
Published: May 2020

Background

Actigraphy has received increasing attention in classifying rest-activity cycles. However, in patients with disorders of consciousness (DOC), actigraphy data may be considerably confounded by passive movements, such as nursing activities and therapies. Consequently, this study verified whether circadian rhythmicity is (still) visible in actigraphy data from patients with DOC after correcting for passive movements.

Methods

Wrist actigraphy was recorded over 7–8 consecutive days in patients with DOC (diagnosed with unresponsive wakefulness syndrome [UWS; n = 19] and [exit] minimally conscious state [MCS/EMCS; n = 11]). The presence and actions of clinical and research staff as well as visitors were indicated using a tablet in the patient’s room. Following removal and interpolation of passive movements, non-parametric rank-based tests were computed to identify differences between circadian parameters of uncorrected and corrected actigraphy data.

Results

Uncorrected actigraphy data overestimated the interdaily stability and intradaily variability of patients’ activity and underestimated the deviation from a circadian 24-h rhythm. Only 5/30 (17%) patients deviated more than 1 h from 24 h in the uncorrected data, whereas this was the case for 17/30 (57%) patients in the corrected data. When contrasting diagnoses based on the corrected dataset, stronger circadian rhythms and higher activity levels were observed in MCS/EMCS as compared to UWS patients. Day-to-night differences in activity were evident for both patient groups.

Conclusion

Our findings indicate that uncorrected actigraphy data overestimates the circadian rhythmicity of patients’ activity, as nursing activities, therapies, and visits by relatives follow a circadian pattern itself. Therefore, we suggest correcting actigraphy data from patients with reduced mobility.
High-level production of poly-γ-glutamic acid from untreated molasses by Bacillus siamensis IR10
Authors: Wang Dexin , Kim Hyangmi , Lee Sungbeom , Kim Dae-Hyuk , Joe Min-Ho
Published: May 2020

Background

Poly-γ-glutamic acid (γ-PGA) is a promising biopolymer and has been applied in many fields.Bacillus siamensisSB1001 was a newly isolated poly-γ-glutamic acid producer with sucrose as its optimal carbon source. To improve the utilization of carbon source, and then molasses can be effectively used for γ-PGA production,60cobalt gamma rays was used to mutate the genes ofB. siamensisSB1001.

Results

Bacillus siamensisIR10 was screened for the production of γ-PGA from untreated molasses. In batch fermentation, 17.86 ± 0.97 g/L γ-PGA was obtained after 15 h, which is 52.51% higher than that of its parent strain. Fed-batch fermentation was performed to further improve the yield of γ-PGA with untreated molasses, yielding 41.40 ± 2.01 g/L of γ-PGA with a productivity of 1.73 ± 0.08 g/L/h. An average γ-PGA productivity of 1.85 g/L/h was achieved in the repeated fed-batch fermentation. This is the first report of such a high γ-PGA productivity. The analysis of the enzyme activities showed that they were affected by the carbon sources, enhanced ICDH and GDH, and decreased ODHC, which are important for γ-PGA production.

Conclusion

These results suggest that untreated molasses can be used for economical and industrial-scale production of γ-PGA byB. siamensisIR10.
Correction to: Exosome-transmitted miR-128-3p increase chemosensitivity of oxaliplatin-resistant colorectal cancer
Authors: Liu Tong , Zhang Xin , Du Lutao , Wang Yunshan , Liu Xiaoming , Tian Hui , Wang Lili , Li Peilong , Zhao Yinghui , Duan Weili , Xie Yujiao , Sun Zhaowei , Wang Chuanxin
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
What is needed for implementing drug checking services in the context of the overdose crisis? A qualitative study to explore perspectives of potential service users
Authors: Wallace Bruce , van Roode Thea , Pagan Flora , Phillips Paige , Wagner Hailly , Calder Shane , Aasen Jarred , Pauly Bernie , Hore Dennis
Published: May 2020

Background

The current illicit drug overdose crisis within North America and other countries requires expanded and new responses to address unpredictable and potentially lethal substances, including fentanyl analogues, in the unregulated drug market. Community-wide drug checking is being increasingly explored as one such public health response. We explored how drug checking could be implemented as a potential harm reduction response to the overdose crisis, from the perspective of potential service users.

Methods

The research was guided by the Consolidated Framework for Implementation Research (CFIR). We conducted a qualitative, pre-implementation study to inform development and implementation of drug checking services that are acceptable to people who use substances and meet their needs. University and community researchers conducted 27 in-depth interviews with potential service users at prospective drug checking sites. We inductively developed emerging themes to inform the implementation of drug checking services within the five domains of the CFIR, and identified the most relevant constructs.

Results

Implementing community drug checking faces significant challenges within the current context of criminalization and stigmatization of substance use and people who use/sell drugs, and trauma experienced by potential service users. Participants identified significant risks in accessing drug checking, and that confidential and anonymous services are critical to address these. Engaging people with lived experience in the service can help establish trust. The relative advantage of drug checking needs to outweigh risks through provision of accurate results conveyed in a respectful, non-judgemental way. Drug checking should provide knowledge relevant to using and/or selling drugs and informing one’s own harm reduction.

Conclusions

For service users, the extent to which the implementation of drug checking can respond to and mitigate the risks of being criminalized and stigmatized is critical to the acceptability and success of community drug checking. The culture and compatibility of the service, setting and staff with harm reduction principles and practices is essential.
Psychometric properties of the Connor-Davidson Resilience Scale (CD-RISC) in a non-clinical population in Sweden
Authors: Velickovic Katarina , Rahm Hallberg Ingalill , Axelsson Ulrika , Borrebaeck Carl A. K. , Rydén Lisa , Johnsson Per , Månsson Johanna
Published: May 2020

Background

The Connor-Davidson Resilience Scale (CD-RISC) is the most widely used scale which assesses psychological resilience. Although it is recommended to be applied as a unidimensional scale, its factor structure, reliability, as well as discriminant and predictive validity need to be assessed when used in a new context. Moreover, the original five-factor structure has not been replicated in previous investigations. This study aimed to explore psychometric properties of the scale in a Swedish context.

Methods

Construct validity of the five-factor model of CD-RISC was assessed using Exploratory and Confirmatory Factor Analyses. Its discriminant validity was assessed in relation to a measure of emotion regulation (Brief Version of the Difficulties in Emotion Regulation Scale) using a Confirmatory Factor Analysis. Predictive validity of CD-RISC was assessed in relation to measures of physical and mental health-related quality of life (The 12-Item Short Form Survey) using hierarchical multiple regression analyses. A population based sample cohort was employed (N = 2599).

Results

Exploratory and Confirmatory Factor Analyses suggested a 22-item unidimensional model of CD-RISC. Psychological resilience was found to be independent from the measure of emotion regulation. It was shown to predict both physical and mental health-related quality of life, being especially strongly associated with mental health aspects.

Conclusions

The study showed that the Swedish version of CD-RISC is an instrument with high discriminant and predictive validity, although the original factor structure does not apply in this context. CD-RISC can thus be used to identify individuals with a higher need of psychosocial support, especially relating to mental health needs.
Health-related quality of life and its influencing factors in adult patients with localized scleroderma - a cross-sectional study
Authors: Lis-Święty Anna , Skrzypek-Salamon Alina , Ranosz-Janicka Irmina , Brzezińska-Wcisło Ligia
Published: May 2020

Background

Localized Scleroderma (LoS) is an autoimmune connective tissue disease that affects skin and less commonly subcutaneous tissues. The illness occurs in children and adults, and may have a serious impact on health-related quality of life (HRQoL). The goal of this study was to explore what factors might deteriorate scores on HRQoL measures in adult LoS patients.

Methods

Detailed information on the demographic and clinical features of LoS patients was collected. The HRQoL was assessed using Skindex-29 and Short form 36 (SF-36) questionnaires.

Results

Thirty three women and seven men with LoS were enrolled. Female gender negatively influenced scores for the emotion subscale of Skindex-29. Multiple-factor linear regression analysis confirmed, as with single-factor analysis, that the causes of low SF-36 physical component score (PCS) were subjective symptoms (pruritus, pain, paresthesia), musculoskeletal manifestations and older age at the time of survey, while rural area of residence negatively affected the SF-36 mental component score. Additionally, single-factor analysis showed that the SF-36 PCS was related to the LoS cutaneous assessment tool (LoSCAT) summary score.

Conclusions

Apart from a clinical presentations, sociodemographic characteristics, including older age, female gender and living conditions, may impair HRQoL of LoS patients. Further studies that will examine the role of these factors for physical and mental functioning of adults with LoS are needed.
Quality of life during chemotherapy, hormonotherapy or antiHER2 therapy of patients with advanced, metastatic breast cancer in clinical practice
Authors: Adamowicz Krzysztof , Baczkowska-Waliszewska Zuzanna
Published: May 2020

Introduction

Breast cancer is one of the most important health problems in the world. In recent years, this cancer has achieved a reduction in mortality, which is attributed to the introduction of mass screening and greater efficacy of post-operative treatment. Many patients with breast cancer have indications only for palliative therapy, but the impact of these methods on the quality of life of patients remains a subject of controversy. It remains unknown whether the progress in improving the quality of life in clinical trials also applies to patients treated as part of daily clinical practice. Data on the results of the impact of conducted therapies on the quality of life outside of clinical trials are scarce.

Methods

The results of palliative chemotherapy and first-line hormonotherapy in 351 patients with advanced, metastatic breast cancer treated in the period from January 2010 to December 2016 in two centres were analysed.

Results

The average age of patients was 62 ± 9.8 years; 139 patients received chemotherapy, 91 - therapy containing trastuzumab, and 121 - hormone therapy. A partial response was obtained in 111 patients (32%), stabilization in 150 (43%), and in 90 patients (26%) progression. Median survival time in the whole group of patients was 36 months. Chemotherapy compared to trastuzumab and hormonotherapy was associated with greater total toxicity (p = 0.03). There was a significant relationship between the type of therapy (hormonotherapy, chemotherapy, targeted therapy) and the general average quality of women’s life measured with the EORC-QLQ-C30 questionnaire. In addition, a statistically significant difference was found in some somatic complaints (the scale of QLQ-BR23 symptoms) depending on the type of therapy performed. The lowest intensity of complaints was reported by patients during hormonotherapy, then during targeted therapy, and the largest during chemotherapy.

Conclusions

There is no effect of chemotherapy on the overall quality of life. Hormone therapy and trastuzumab therapy improved the quality of life of the treated patients in clinical practice.
Polish adaptation and validation of the hip disability and osteoarthritis outcome score (HOOS) in osteoarthritis patients undergoing total hip replacement
Authors: Gojło Marek K. , Paradowski Przemysław T.
Published: May 2020

Background

The Hip disability and Osteoarthritis Outcome Score (HOOS) is a frequently used patient-reported outcome measure (PROM) for assessment of hip disorders and treatment effects following hip surgery. The objective of the study was to translate and adapt the Hip disability and Osteoarthritis Outcome Score (HOOS) into Polish and to investigate the psychometric properties of the HOOS in patients with osteoarthritis undergoing total hip replacement (THR).

Materials and methods

The Polish version of the HOOS was developed according to current guidelines. Patients completed the HOOS, Short Form 36 Health Survey (SF-36), the visual analogue scale (VAS) for pain and the global perceived effect (GPE) scale. Psychometric properties including interpretability (floor/ceiling effects), internal consistency (Cronbach’s alpha), test-retest reliability (intra-class correlation coefficient, ICC), convergent construct validity (a priori hypothesized Spearman’s correlations between the HOOS subscales, the generic SF-36 measure and the VAS for pain) and responsiveness (effect size, association between the HOOS and GPE scores) were analyzed.

Results

The study included 157 patients (mean age 66.8 years, 54% women). Floor effects were found prior to THR for the HOOS subscales Sports and Recreation and Quality of Life. The Cronbach’s alpha was over 0.7 for all subscales indicating satisfactory internal consistency. The test–retest reliability was good for the HOOS subscale Pain (0.82) and excellent for all other subscales with ICCs ranging from 0.91 to 0.96. The minimal detectable change ranged from 12.0 to 26.2 on an individual level and from 1.4 to 3.0 on a group level. Seven out of eight a priori hypotheses were confirmed indicating good construct validity. Responsiveness was high since the expected pattern of effect sizes in all subscales was found.

Conclusions

The Polish version of the HOOS demonstrated good reliability, validity and responsiveness for use in patient groups having THR.
Study on follicular fluid metabolomics components at different ages based on lipid metabolism
Authors: Zhang Xingxing , Wang Tianqi , Song Jingyan , Deng Jifeng , Sun Zhengao
Published: May 2020

Background

Follicular fluid is an important external environment for the growth and development of oocytes. A thorough identification of specific components in follicular fluid can better the existing understand of intracellular signal transduction and reveal potential biomarkers of oocyte health in women undergoing assisted reproductive therapy. To study on follicular fluid metabolomics components at different ages based on lipid metabolism, we have adopted a new method of SWATH to MRM(the sequential window acquisition of all theoretical fragment-ion spectra to multiple reaction monitor)metabolomics to provide extensive coverage and excellent quantitative data. This was done to investigate the differences in follicular fluid of patients undergoing in vitro fertilization (IVF) and embryo transfer in different age groups and to further explore the relationship between follicular fluid, age and reproductive function.

Method

A combination of Ultra-high-performance liquid chromatography and high resolution mass spectrometry techniques were used to analyze the follicular fluid of 230 patients enrolled for the IVF cycle. The patients were of different ages grouped into two groups:the younger and older patients.The obtained multidimensional chromatographic data were processed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The charge ratios and mass numbers enabled for the identification of different fragments in the samples. Matching information obtained through database search and the fragment information obtained by fragment ion scan structurally identified substances in the samples. This was used to determine the differential compounds.

Results

The quality of oocytes decline with age,and the lipid composition in follicular fluid also changes,The lipid metabolism that changes with age may be related to the quality of oocytes.The main differences were in lipid metabolites. Some were up-regulated: Arachidonate, LysoPC(16:1), LysoPC(20:4) and LysoPC(20:3) while others were down-regulated: LysoPC(18:3) and LysoPC(18:1).

Conclusions

Metabolomic analysis of follicular fluid revealed that with the increase in age, several differential metabolites are at play. Among these metabolites, lipid metabolism undergoes significant changes that affect the development of oocytes thus causing reduced fertility in older women. These differential metabolites related to follicular development may provide possible detection and treatment targets for promoting oocyte health, and provide scientific basis for understanding the environment of oocyte development.
Unstably controlled systolic blood pressure trajectories are associated with markers for kidney damage in prediabetic population: results from the INDEED cohort study
Authors: Sun Zi-Jun , Wang Jin-Wei , Chang Dong-Yuan , Chen Shuo-Hua , Zhang Hui-Fen , Wu Shou-Ling , He Kevin , Zhang Lu-Xia , Chen Min , Zhao Ming-Hui
Published: May 2020

Background

The association between blood pressure change and kidney damage in patients with abnormal blood glucose remains unclear. The current study aimed to identify systolic blood pressure (SBP) trajectories among the prediabetic population and to determine their association with kidney damage after a long-term follow-up.

Methods

The incidence, development, and prognosis of diabetic kidney disease (INDEED) study is nested in the Kailuan cohort study with a focus on population with diabetes and prediabetes. We screened out people with prediabetes in 2006 and with more than three SBP records from 2006 to 2014 biennially. We used the latent mixture modeling to fit five groups of trajectories of SBP. In 2016, estimated glomerular filtration rate (eGFR), urinary albumin creatinine ratio (uACR), and urinary α1-microglobulin (α1MG), transferrin and α1-acid glycoprotein were measured, and the association between SBP trajectories and these markers was analyzed by linear regression and logistic regression models.

Results

Totally, 1451 participants with prediabetes and without kidney damage were identified in 2006. Five heterogeneous SBP trajectories were detected based on the longitudinal data from 2006 to 2014, as low-stable group (n = 323), moderate-stable group (n = 726), moderate-increasing group (n = 176), moderate-decreasing group (n = 181), and high-stable group (n = 45). Linear regression analysis showed that the moderate and high SBP groups had lower eGFR, higher uACR, higher urinary α1MG, higher transferrin, and higher α1-acid glycoprotein than the low-stable group. Multivariable analysis attenuated the association but did not change the statistical significance.

Conclusions

Prediabetic patients with persistent high-level SBP trajectory or gradually increased SBP trajectory had severer kidney damage during follow-up.
Beneficial impact of epigallocatechingallate on LDL-C through PCSK9/LDLR pathway by blocking HNF1α and activating FoxO3a
Authors: Cui Chuan-Jue , Jin Jing-Lu , Guo Lin-Na , Sun Jing , Wu Na-Qiong , Guo Yuan-Lin , Liu Geng , Dong Qian , Li Jian-Jun
Published: May 2020

Background

Green tea drinking has been proven to lower lipid and exert cardiovascular protection, while the potential mechanism has not been fully determined. This study was to investigate whether the beneficial impact of epigallocatechingallate (EGCG), a type of catechin in green tea on lipids is associated with proprotein convertase subtilisin/kexin type 9 (PCSK9) pathways.

Methods

We studied the effects and underlying molecular mechanism of EGCG or green tea on regulating cholesterol from human, animal and in vitro.

Results

In the age- and gender-matched case control observation, we found that individuals with frequent tea consumption (n = 224) had the lower plasma PCSK9 and low density lipoprotein cholesterol (LDL-C) levels compared with ones without tea consumption (n = 224, p < 0.05). In the high fat diet (HFD) fed rats, EGCG administration significantly lowered circulating PCSK9 concentration and liver PCSK9 expression, along with up-regulated LDL receptor (LDLR) expression but decreased level of LDL-C. In hepatic cell study, similar results were obtained regarding the impact of EGCG on LDLR and PCSK9 expression. The assay transposase-accessible chromatic with high-throughput sequencing (ATAC-seq) and subsequent results suggested that two transcription factors, hepatocyte nuclear factor-1α (HNF-1α) and forkhead box class O (FoxO) 3a involved in inhibitory action of EGCG on PCSK9 expression.

Conclusions

The present study demonstrates that EGCG suppresses PCSK9 production by promoting nuclear FoxO3a, and reducing nuclear HNF1α, resulting in up-regulated LDLR expression and LDL uptake in hepatocytes. Thereby inhibiting liver and circulating PCSK9 levels, and ultimately lowering LDL-C levels.
Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak
Authors: Har-Noy Michael , Or Reuven
Published: May 2020

Background

We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next ‘Disease X’. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim®) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim®creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-ϒ, leading to development of an “anti-viral state”, by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allo-specific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-ϒ, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/CTL in circulation capable of responding to the next viral encounter.

Conclusion

Allo-priming has potential to provide universal protection from viral disease and is a strategy to reverse immunosenescence and counter-regulate chronic inflammation (inflammaging). Allo-priming can be used as an adjuvant for anti-viral vaccines and as a counter-measure for unknown biological threats and bio-economic terrorism.
Type 1 interferonopathy presenting as juvenile idiopathic arthritis with interstitial lung disease: report of a new phenotype
Authors: Clarke S. L. N. , Robertson L. , Rice G. I. , Seabra L. , Hilliard T. N. , Crow Y. J. , Ramanan A. V.
Published: May 2020

Background

STING-associated vasculopathy with onset in infancy (SAVI) is a type 1 interferonopathy manifesting as a pulmonary and vascular syndrome resulting from gain-of-function mutations in TMEM173, the gene encoding STING. Familial reports in the literature are sparse.

Case presentation

We report a case series of SAVI in a three generation kindred, with a phenotype of interstitial lung disease (ILD) and rheumatoid factor positive polyarticular juvenile idiopathic arthritis (JIA). Current and historical medical records were reviewed for clinical and laboratory information. Whole blood from cases 1 and 2, plus stored appendicectomy tissue from case 3, underwent DNA sequencing of the TMEM173 gene. Peripheral blood RNA was obtained from cases 1 and 2 for functional assessment of the TMEM173 mutation. DNA sequencing identified the same heterozygous TMEM173 mutation (c.463G > A; p.Val155Met) in all three cases, consistent with a diagnosis of the autosomal dominant condition SAVI. Functional assessment of this mutation identified a prominent interferon signature which was confirmed on repeat testing.

Conclusions

SAVI presented in this family as ILD with early onset juvenile rheumatoid arthritis. This condition should be considered in all rheumatoid arthritis patients with early-onset ILD and in all JIA patients with ILD.
Daily variations of gut microbial translocation markers in ART-treated HIV-infected people
Authors: Ouyang Jing , Isnard Stéphane , Lin John , Fombuena Brandon , Chatterjee Debashree , Wiche Salinas Tomas Raul , Planas Delphine , Cattin Amélie , Fert Augustine , Moreira Gabriel Etiene , Raymond Marchand Laurence , Zhang Yonglong , Finkelman Malcolm , Chen Yaokai , Kaufmann Daniel E. , Cermakian Nicolas , Ancuta Petronela , Routy Jean-Pierre
Published: May 2020

Background

Increased intestinal barrier permeability and subsequent gut microbial translocation are significant contributors to inflammatory non-AIDS comorbidities in people living with HIV (PLWH). Evidence in animal models have shown that markers of intestinal permeability and microbial translocation vary over the course of the day and are affected by food intake and circadian rhythms. However, daily variations of these markers are not characterized yet in PLWH. Herein, we assessed the variation of these markers over 24 h in PLWH receiving antiretroviral therapy (ART) in a well-controlled environment.

Methods

As in Canada, PLWH are predominantly men and the majority of them are now over 50 years old, we selected 11 men over 50 receiving ART with undetectable viremia for more than 3 years in this pilot study. Blood samples were collected every 4 h over 24 h before snacks/meals from 8:00 in the morning to 8:00 the next day. All participants consumed similar meals at set times, and had a comparable amount of sleep, physical exercise and light exposure. Plasma levels of bacterial lipopolysaccharide (LPS) and fungal (1→3)-β-D-Glucan (BDG) translocation markers, along with markers of intestinal damage fatty acid binding protein (I-FABP) and regenerating islet-derived protein-3α (REG3α) were assessed by ELISA or the fungitell assay.

Results

Participants had a median age of 57 years old (range 50 to 63). Plasma levels of BDG and REG3α did not vary significantly over the course of the study. In contrast, a significant increase of LPS was detected between 12:00 and 16:00 (Z-score: − 1.15 ± 0.18 vs 0.16 ± 0.15, p = 0.02), and between 12:00 and 24:00 (− 1.15 ± 0.18 vs 0.89 ± 0.26, p < 0.001). The plasma levels of I-FABP at 16:00 (− 0.92 ± 0.09) were also significantly lower, compared to 8:00 the first day (0.48 ± 0.26, p = 0.002), 4:00 (0.73 ± 0.27, p < 0.001) or 8:00 on secondary day (0.88 ± 0.27, p < 0.001).

Conclusions

Conversely to the fungal translocation marker BDG and the gut damage marker REG3α, time of blood collection matters for the proper evaluation for LPS and I-FABP as markers for the risk of inflammatory non-AIDS co-morbidities. These insights are instrumental for orienting clinical investigations in PLWH.
A case report of mania with abnormal cerebral blood flow and cognitive impairment 24 years after head trauma
Authors: Yoshino Hiroki , Aoki Chieko , Kitamura Soichiro , Yamamuro Kazuhiko , Tanaka Shohei , Kishimoto Toshifumi
Published: May 2020

Background

Mania usually occurs secondary to organic etiologies such as head trauma within a short time of the primary condition’s onset; however, there have been a few cases reported in the literature of long time spans before the manifestation of mania. The orbitofrontal cortex has been reported to be associated with manic states in bipolar disorder and with mania-inducing lesions. Head trauma commonly disrupts various cognitive functions, including attention and information processing. Traumatic brain injury patients have been shown to have greater posterior cingulate cortex and precuneus functional connectivity to the rest of the default mode network. We describe a case of secondary mania after head trauma 24 years ago with low blood flow in the orbitofrontal cortex, high blood flow in the posterior cingulate cortex, and impaired cognitive functioning, including impaired attention and lowered processing speed.

Case presentation

We describe a 30-year-old Japanese man with secondary mania and a medical history of head trauma 24 years ago. After head trauma at 6 years of age, the patient first showed apathy as a sign of frontal lobe impairment. After recovering, he experienced no psychiatric problems during adolescence, although he did show disinhibited behavior. At the onset of mania, low blood flow in the OFC and high blood flow in the PCC were observed as well as impaired cognitive function, including inattention and lowered processing speed. Abnormal cerebral blood flow was less prominent and cognitive dysfunction was partially recovered following recovery from mania, but his processing speed remained low.

Conclusions

Although functional recovery from head trauma in childhood is better than that in adulthood, the brain may remain vulnerable for a long time. The risk of psychotic symptoms such as mania should be considered, even if sufficient superficial brain functional recovery is shown.
DiCoExpress: a tool to process multifactorial RNAseq experiments from quality controls to co-expression analysis through differential analysis based on contrasts inside GLM models
Authors: Lambert Ilana , Paysant-Le Roux Christine , Colella Stefano , Martin-Magniette Marie-Laure
Published: May 2020

Background

RNAseq is nowadays the method of choice for transcriptome analysis. In the last decades, a high number of statistical methods, and associated bioinformatics tools, for RNAseq analysis were developed. More recently, statistical studies realised neutral comparison studies using benchmark datasets, shedding light on the most appropriate approaches for RNAseq data analysis.

Results

DiCoExpress is a script-based tool implemented in R that includes methods chosen based on their performance in neutral comparisons studies. DiCoExpress uses pre-existing R packages including FactoMineR, edgeR and coseq, to perform quality control, differential, and co-expression analysis of RNAseq data. Users can perform the full analysis, providing a mapped read expression data file and a file containing the information on the experimental design. Following the quality control step, the user can move on to the differential expression analysis performed using generalized linear models thanks to the automated contrast writing function. A co-expression analysis is implemented using the coseq package. Lists of differentially expressed genes and identified co-expression clusters are automatically analyzed for enrichment of annotations provided by the user. We used DiCoExpress to analyze a publicly available RNAseq dataset on the transcriptional response ofBrassica napus L.to silicon treatment in plant roots and mature leaves. This dataset, including two biological factors and three replicates for each condition, allowed us to demonstrate in a tutorial all the features of DiCoExpress.

Conclusions

DiCoExpress is an R script-based tool allowing users to perform a full RNAseq analysis from quality controls to co-expression analysis through differential analysis based on contrasts inside generalized linear models. DiCoExpress focuses on the statistical modelling of gene expression according to the experimental design and facilitates the data analysis leading the biological interpretation of the results.
Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) diagnosed in children and adolescents
Authors: Jinmei Zhang , Yunfei Ling , Yue Wang , Yongjun Qian
Published: May 2020

Background

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare but potentially fatal congenital coronary anomaly associated with early infant mortality and sudden adult death. By the development or lack of coronary collateral, it can be classified as infantile or adult type. However, even with the compensatory mechanism in adult patients, there is an estimated 80 to 90% incidence of sudden death at the mean age of 35 years.

Methods

We enrolled 9 patients with ALCAPA within the age group 5 to 16 years.

Results

Only one patient developed symptoms (apsychia), whereas other patients were asymptomatic, and there was no evident left ventricular dysfunction found in any of the cases.

Conclusion

With the development of imaging techniques, asymptomatic adult-type ALCAPA patients could be identified and diagnosed in childhood or adolescence. As a potential cause of sudden death, ALCAPA should be surgically repaired soon after the diagnosis.