bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant cold shock domain containing protein is a potential antigen to detect specific antibody during early and late infections of Haemonchus contortus in goat
Authors: Naqvi Muhammad Ali-ul-Husnain , Aimulajiang Kalibixiati , Memon Muhammad Ali , Hasan Muhammad Waqqas , Naqvi Sana Zahra , Lakho Shakeel Ahmed , Chu Wen , Xu Lixin , Song Xiaokai , Li Xiangrui , Yan Ruofeng
Published: February 2020

Background

Haemonchus contortus (H. contortus) is one of the most important parasites that cause huge economic losses to small ruminant industry worldwide. Effective prognosis and treatment depend upon the early diagnosis of H. contortus infection. To date, no widely-approved methods for the identification of prepatent H. contortus infection are available to identify prepatent H. contortus infection properly. The aim of this study was to evaluate the diagnostic potential of recombinant cold shock H. contortus protein (rHc-CS) during early and late infections of H. contortus in goat.

Results

Purified rHc-CS exhibited a clear band, with a molecular weight about 38 kDa. H. contortus eggs were not detected by fecal egg count technique from feces collected at 0 to 14 days post infection (D.P.I). However, eggs were detected at 21, 28 and 35 D.P.I. Hence, results of immunoblotting assay showed specific anti rHc-CS antibody detection in all goat sera collected at early stage (14 D.P.I) and late stage (21–103 D.P.I) of H. contortus infection. Furthermore, no cross reactivity was observed against Trichinella spiralis, Fasciola hepatica and Toxoplasma gondii or uninfected goats. Among several evaluated rHc-CS indirect-ELISA format variables, favorable antigen coating concentration was found 0.28 μg/well at 37 °C 1 h and overnight at 4 °C. Moreover, optimum dilution ratio of serum and rabbit anti-goat IgG was recorded as 1:100 and 1:4000, respectively. The best blocking buffer was 5% Bovine Serum Albumin (BSA) while the best time for blocking, serum incubation and TMB reaction were recorded as 60, 120 and 10 min, respectively. The cut-off value for positive and negative interpretation was determined as 0.352 (OD450). The diagnostic specificity and sensitivity of the rHc-CS, both were recorded as 100%.

Conclusion

These results validated that rHc-CS is a potential immunodiagnostic antigen to detect the specific antibodies during early and late H. contortus infections in goat.
Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation
Authors: Hung Su-Jhen , Hsu Yin-Mei , Huang Sheng-Wen , Tsai Huey-Pin , Lee Leo Yi Yang , Hurt Aeron C. , Barr Ian G. , Shih Shin-Ru , Wang Jen-Ren
Published: February 2020

Background

Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription.

Methods

To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties.

Results

The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity. The 31 K and 450G showed better viral translation and replication in vitro and in vivo.

Conclusions

These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo. This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention.
Examining purchasing reforms towards universal health coverage by the National Hospital Insurance Fund in Kenya
Authors: Mbau Rahab , Kabia Evelyn , Honda Ayako , Hanson Kara , Barasa Edwine
Published: February 2020

Background

Kenya has prioritized the attainment of universal health coverage (UHC) through the expansion of health insurance coverage by the National Hospital Insurance Fund (NHIF). In 2015, the NHIF introduced reforms in premium contribution rates, benefit packages, and provider payment methods. We examined the influence of these reforms on NHIF’s purchasing practices and their implications for strategic purchasing and health system goals of equity, efficiency and quality.

Methods

We conducted an embedded case study with the NHIF as the case and the reforms as embedded units of analysis. We collected data at the national level and in two purposively selected counties through 41 in-depth interviews with health financing stakeholders, facility managers and frontline providers; 4 focus group discussions with 51 NHIF members; and, document reviews. We analysed the data using a Framework approach.

Results

The new NHIF reforms were characterized by weak purchasing actions. Firstly, the new premium contribution rates were inadequately communicated and unaffordable for certain citizen groups. Secondly, while the new benefit packages were reported to be based on service needs, preferences and values of the population, they were inadequately communicated and unequally distributed across different citizen groups. In addition, the presence of service delivery infrastructure gaps in public healthcare facilities and the pro-urban and pro-private distribution of contracted health facilities compromised delivery of, and access to, these new services. Lastly, the new provider payment methods and rates were considered inadequate, with delayed payments and weak links to financial accountability mechanisms which compromised their ability to incentivize equity, efficiency and quality of healthcare delivery.

Conclusion

While NHIF sought to expand population and service coverage and reduce out-of-pocket payments with the new reforms, weaknesses in the reforms’ design and implementation limited NHIF’s purchasing actions with negative implications for the health system goals of equity, efficiency and quality. For the reforms to accelerate the country’s progress towards UHC, policy makers at the NHIF and, national and county government should make deliberate efforts to align the design and implementation of such reforms with strategic purchasing actions that are aimed at improving health system goals.
Intersectionality, special populations, needs and suggestions: the Flint Women’s study
Authors: Hailemariam Maji , Felton Julia W. , Key Kent , Greer DeOnica , Jefferson Bernadel L. , Muhammad Janice , Miller Raven , Richie Fallon , Robinson DeWaun , Saddler Sharon , Spencer Bryan , Summers Monicia , White Jonne Mc Coy , Johnson Jennifer E.
Published: February 2020

Background

Equitable access to services that promote health and wellbeing is an important component of social justice. A community-engaged participatory qualitative study was conducted in Flint, Michigan, USA, to understand the needs of special populations (young women, perinatal women and new mothers, older women, women with disabilities, and LGBTQIA women) and elicit their ideas about solutions.

Methods

In-depth interviews (n = 100) were conducted. Participants were either women living in the Flint area, human service providers in the area, or both. A team of community and academic coders analyzed the data using an a priori framework.

Results

Participants identified needs of different groups of women and suggested ways to address them. Access to healthy food, reducing healthcare costs, and improving transportation, job opportunities and affordable quality housing were crosscutting themes across all groups of women. Mentoring support was said to protect vulnerable young women from the risk of human trafficking. Older women were said to gain a sense of purpose, build their social support and reduce their loneliness by engaging in mentoring younger women. Women with disabilities were reported to benefit from infrastructure accessibility and authentic inclusion in all areas of life. Providing help that considers their dignity, pride and self-worth were suggested. LGBTQIA women were reported to have housing needs due to discrimination; mostly turned down as renters and can be rejected from faith-based homeless shelters. LGBTQIA women would also benefit from increased sensitivity among healthcare providers. For all groups of women, streamlining access to social services and other resources, building social support networks and increasing awareness about existing resources were recommended.

Conclusion

Efforts directed towards improving women’s health and wellbeing should include perspectives and suggestions of diverse groups of women from the community. Acting on suggestions that emanate from the community’s lived experiences may reduce inequalities in health and wellbeing.
Is the closest health facility the one used in pregnancy care-seeking? A cross-sectional comparative analysis of self-reported and modelled geographical access to maternal care in Mozambique, India and Pakistan
Authors: Makacha Liberty , Makanga Prestige Tatenda , Dube Yolisa Prudence , Bone Jeffrey , Munguambe Khátia , Katageri Geetanjali , Sharma Sumedha , Vidler Marianne , Sevene Esperança , Ramadurg Umesh , Charantimath Umesh , Revankar Amit , von Dadelszen Peter
Published: February 2020

Background

Travel time to care is known to influence uptake of health services. Generally, pregnant women who take longer to transit to health facilities are the least likely to deliver in facilities. It is not clear if modelled access predicts fairly the vulnerability in women seeking maternal care across different spatial settings.

Objectives

This cross-sectional analysis aimed to (i) compare travel times to care as modelled in a GIS environment with self-reported travel times by women seeking maternal care in Community Level Interventions for Pre-eclampsia: Mozambique, India and Pakistan; and (ii) investigate the assumption that women would seek care at the closest health facility.

Methods

Women were interviewed to obtain estimated travel times to health facilities (R). Travel time to the closest facility was also modelled (P) (closest facility tool (ArcGIS)) and time to facility where care was sought estimated (A) (route network layer finder (ArcGIS)). Bland–Altman analysis compared spatial variation in differences between modelled and self-reported travel times. Variations between travel times to the nearest facility (P) with modelled travel times to the actual facilities accessed (A) were analysed. Log-transformed data comparison graphs for medians, with box plots superimposed distributions were used.

Results

Modelled geographical access (P) is generally lower than self-reported access (R), but there is a geography to this relationship. In India and Pakistan, potential access (P) compared fairly with self-reported travel times (R) [P (H0: Mean difference = 0)] < .001, limits of agreement: [− 273.81; 56.40] and [− 264.10; 94.25] respectively. In Mozambique, mean differences between the two measures of access were significantly different from 0 [P (H0: Mean difference = 0) = 0.31, limits of agreement: [− 187.26; 199.96]].

Conclusion

Modelling access successfully predict potential vulnerability in populations. Differences between modelled (P) and self-reported travel times (R) are partially a result of women not seeking care at their closest facilities. Modelling access should not be viewed through a geographically static lens. Modelling assumptions are likely modified by spatio-temporal and/or socio-cultural settings. Geographical stratification of access reveals disproportionate variations in differences emphasizing the varied nature of assumptions across spatial settings.

Trial registration ClinicalTrials.gov, NCT01911494. Registered 30 July 2013, https://clinicaltrials.gov/ct2/show/NCT01911494
A novel IFNα-induced long noncoding RNA negatively regulates immunosuppression by interrupting H3K27 acetylation in head and neck squamous cell carcinoma
Authors: Ma Hailong , Chang Hanyue , Yang Wenyi , Lu Yusheng , Hu Jingzhou , Jin Shufang
Published: February 2020

Background

Interferon alpha (IFNα) is a well-established regulator of immunosuppression in head and neck squamous cell carcinoma (HNSCC), while the role of long noncoding RNAs (lncRNAs) in immunosuppression remains largely unknown.

Methods

Differentially expressed lncRNAs were screened under IFNα stimulation using lncRNA sequencing. The role and mechanism of lncRNA in immunosuppression were investigated in HNSCC in vitro and in vivo.

Results

We identified a novel IFNα-induced upregulated lncRNA, lncMX1–215, in HNSCC. LncMX1–215 was primarily located in the cell nucleus. Ectopic expression of lncMX1–215 markedly inhibited expression of the IFNα-induced, immunosuppression-related molecules programmed cell death 1 ligand 1 (PD-L1) and galectin-9, and vice versa. Subsequently, histone deacetylase (HDAC) inhibitors promoted the expression of PD-L1 and galectin-9. Binding sites for H3K27 acetylation were found on PD-L1 and galectin-9 promoters. Mechanistically, we found that lncMX1–215 directly interacted with GCN5, a known H3K27 acetylase, to interrupt its binding to H3K27 acetylation. Clinically, negative correlations between lncMX1–215 and PD-L1 and galectin-9 expression were observed. Finally, overexpression of lncMX1–215 suppressed HNSCC proliferation and metastasis capacity in vitro and in vivo.

Conclusions

Our results suggest that lncMX1–215 negatively regulates immunosuppression by interrupting GCN5/H3K27ac binding in HNSCC, thus providing novel insights into immune checkpoint blockade treatment.
The enigma of soluble LDLR: could inflammation be the key?
Authors: Mbikay Majambu , Mayne Janice , Chrétien Michel
Published: February 2020

Soluble low-density lipoprotein receptor (sLDLR) is the circulating ectodomain of transmembrane LDLR. Its blood level strongly correlates with that of triglycerides (TG). This correlation has eluded satisfactory explanation. Hypertriglyceridemia and shedding of the ectodomain of many transmembrane receptors often accompany inflammatory states. The shedding mostly occurs through cleavage by a disintegrin-and-metalloproteinase-17 (ADAM-17), an enzyme activated by inflammation. It reduces the cellular uptake of TG-loaded lipoproteins, causing their accumulation in circulation; hence the correlation between plasma sLDLR and TG. Soluble LDLR could become a new surrogate marker of inflammation.
Short-term outcomes of laparoscopic intersphincteric resection with intraoperative radiotherapy using low-energy X-rays for primary locally advanced low rectal cancer: a single center experience
Authors: Xue Wangsheng , Wang Shuang , Zhao Zeyun , Li Yongbo , Shang An , Li Donglin , Yang Jianzheng , Wang Tiejun , Wang Min
Published: February 2020

Background

Even with the augmentative application of anal-preservation surgery in low rectal cancer, the role and indications of laparoscopic intersphincteric resection (Lap ISR) are still under debate, especially for T3 or node-positive (T3N0M0, T1–3N+M0) cancer, mainly due to the oncological safety and functional outcomes. INTRABEAM (Carl Zeiss, Germany) intraoperative radiotherapy (IORT) using low-energy X-rays features in accurate irradiation, less exposure, and reduced complications. Taking advantages of Lap ISR and INTRABEAM IORT, this innovative approach aims to increase the probability of the anal preservation with acceptable postoperative outcomes.

Materials and methods

From December 2015 to August 2019, we retrospectively analyzed the short-term outcomes of 12 patients evaluated preoperatively with T3 or node-positive (T3N0M0, T1–3N+M0) primary locally advanced low rectal cancer. They all had received Lap ISR and INTRABEAM IORT with a dose of 16–18 Gy applied by an applicator through the anus (natural orifice). Then, with no pre- or postoperative radiotherapy given, the patients were suggested to receive 6–8 cycles of the XELOX chemotherapy regimen (oxaliplatin, 130 mg/m2 and capecitabine, 1000 mg/m2).

Results

All patients achieved R0 resection. The median radiation time was 27 min and 15 s, and the mean radiative dose was 17.3 Gy (range 16–18 Gy). The median follow-up time was 18.5 months (range 3–45 months). Two patients experienced local recurrence. Two male patients experienced anastomotic stenosis. Furthermore, one of them experienced perianal abscess and the other one experienced pulmonary metastasis after refusing to receive chemotherapy. One female patient with internal anal sphincter invasion experienced distant metastases to the liver and gluteus maximus muscle 35 months after IORT. No acute radiation injuries or symptoms were observed. Although they experienced a reduction in anal function, every patient was satisfied with the postoperative outcomes.

Conclusions

For patients evaluated preoperatively with T3 or node-positive (T3N0M0, T1–3N+M0) primary locally advanced low rectal cancer, Lap ISR with INTRABEAM IORT may be a safe and feasible approach for anal preservation without compromising oncological outcomes.
Anal function and quality of life analysis after laparoscopic modified Parks for ultra-low rectal cancer patients
Authors: Ding Haibo , Li Jian , Chen Yuxiang , Yang Zhi , Peng Zha , Liao Xin
Published: February 2020

Background

To assess postoperative anal function and quality of life of ultra-low rectal cancer patients treated by laparoscopic modified Parks surgery.

Methods

From February 2017 to March 2019, 114 patients with ultra-low rectal cancer above T2 were treated respectively with ultra-low anterior resection (Dixon), modified coloanal anastomosis (modified Parks), and Miles according to the preoperative stage and anastomotic position. The postoperative anal function and Fecal Incontinence Quality of Life Scale (FIQL) of each patient were collected and synthetically analyzed.

Results

Compared with the Dixon group, the postoperative anal function and FIQL in the Parks group were poor at the early stage. However, from 6 to 12 months after surgery, the scores of anal function and FIQL in the Parks group were similar to those in the Dixon group (P > 0.05). Compared with the Miles group, the FIQL of the two groups were similar in the early postoperative stage. However, with the passage of time, from 3 to 9 months after surgery, the four domains of FIQL in the Parks group were higher than those in the Miles group successively (P < 0.05).

Conclusions

Laparoscopic modified Parks is a safe, effective, and economical anus-preserving surgery. Although its early anal function and FIQL were poor, it could gradually recover to the similar level as Dixon. Moreover, it can save the anus and obtain a better postoperative quality of life for some patients who previously could only undergo Miles.
Prognosis of limited-stage small cell lung cancer with comprehensive treatment including radical resection
Authors: Zhong Lili , Suo Jiaojiao , Wang Ya , Han Jialong , Zhou Huijie , Wei Hao , Zhu Jiang
Published: February 2020

Background

The NCCN (National Comprehensive Cancer Network) Clinical Practice Guidelines in Oncology (NCCN guidelines) recommend radical resection for T1-2N0M0 patients with limited-stage small cell lung cancer (LS-SCLC). However, only about 5% of patients with small cell cancer (SCLC) were initially diagnosed as T1-2N0M0. The purpose of our study was to analyze and compare the effects of the comprehensive treatment including radical surgery and concurrent chemoradiotherapy on the prognosis of patients with LS-SCLC.

Methods

We comprehensively reviewed the medical data of patients with SCLC diagnosed by pathology in our hospital from January 2011 to April 2018. The Ethics Committee of West China Hospital of Sichuan University approved the study. Finally, 50 patients with good follow-up and complete medical data were selected as the surgical group (S group). According to the clinical characteristics of the patients in the S group, 102 LS-SCLC patients who received concurrent chemoradiotherapy in the same period were included in the CCRT group (concurrent chemoradiotherapy group) as the control group. Then according to the orders of the adjuvant treatments, the patients in the S group were divided into the SA group (radical surgery + adjuvant chemotherapy + adjuvant radiotherapy group, 30 cases in total) and the NS group (neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy group, 20 cases in total) for subgroup analysis. The SPSS 23.0 software was used for statistical analysis, and the t test was used for group comparison; Kaplan-Meier was used for survival analysis. P < 0.05 demonstrates a statistically significant difference.

Results

The median progress-free survival (PFS) in the S group (73 months) was significantly better than that in the CCRT group (10.5 months, P < 0.0001), and the median overall survival (OS) in the S group (79 months) was also significantly better than that in the CCRT group (23 months, P < 0.0001). Subgroup analysis showed that there was no significant difference between the NS group and the SA group.

Conclusions

For LS-SCLC patients, the comprehensive treatment including radical surgery (radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy/neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy)may be superior to concurrent chemoradiotherapy.
Ranking of Iranian provinces based on healthcare infrastructures: before and after implementation of Health Transformation Plan
Authors: Shojaei Payam , bordbar Najmeh , Ghanbarzadegan Arash , Najibi Maryam , Bastani Peivand
Published: February 2020

Background

Health Transformation Plan (HTP) was occurred in 2014 to improve access and equity and reduce out of pocket payments in Iranian Health Care System. In this regard the aim of this study is evaluating and ranking the service provider’s infrastructures among the country provinces as an indicator of equity before and after implementation of the HTP.

Methods

This cross sectional study is conducted in 2017. The study population included 31 provinces of the country. Data related to 4 years from 2012 to 2016 were included from the data bases of Ministry of Health and Medical Education as well as the statistics yearbook of the country. The obtained results of multi-criteria decision-making methods were analyzed as well. SPSS18and Excel2013software were used for data analysis.

Results

Based on the VIKOR method, in 2012, Mazandaran, Tehran and Fars provinces and in 2013, the provinces of Tehran, Fars and Isfahan ranked from first to third respectively. Similarly after HTP, in 2015, the provinces of Tehran, Khorasan Razavi and Fars and in 2016 the provinces of Tehran, Fars and Khorasan Razavi have ranked from first to third respectively. Paramedic, dentist, pharmacist, medical institutions and hospital bed had a significant difference before and after the implementation of Health Transformation Plan, so that the number of these indicators increased after implementation of the HTP (Pvalue < 0.05).

Conclusions

According to the results, there are many differences between the provinces and these disparities have not decreased significantly after HTP. Consequently, it is suggested to the health sector policy makers to make regional plans and allocate the budget of HTP, based on the status of the provinces. In addition, responding to these inequalities requires a transparent and systematic approach to provide the budget for allocating to the population, health needs, and the lack of development and geographical isolation of regions.
Oncogenic functions of the EMT-related transcription factor ZEB1 in breast cancer
Authors: Wu Hua-Tao , Zhong Hui-Ting , Li Guan-Wu , Shen Jia-Xin , Ye Qian-Qian , Zhang Man-Li , Liu Jing
Published: February 2020

Zinc finger E-box binding homeobox 1 (ZEB1, also termed TCF8 and δEF1) is a crucial member of the zinc finger-homeodomain transcription factor family, originally identified as a binding protein of the lens-specific δ1-crystalline enhancer and is a pivotal transcription factor in the epithelial-mesenchymal transition (EMT) process. ZEB1 also plays a vital role in embryonic development and cancer progression, including breast cancer progression. Increasing evidence suggests that ZEB1 stimulates tumor cells with mesenchymal traits and promotes multidrug resistance, proliferation, and metastasis, indicating the importance of ZEB1-induced EMT in cancer development. ZEB1 expression is regulated by multiple signaling pathways and components, including TGF-β, β-catenin, miRNA and other factors. Here, we summarize the recent discoveries of the functions and mechanisms of ZEB1 to understand the role of ZEB1 in EMT regulation in breast cancer.
The growth of non-solid neoplastic lung nodules is associated with low PD L1 expression, irrespective of sampling technique
Authors: Bortolotto Chandra , Maglia Claudio , Ciuffreda Antonio , Coretti Manuela , Catania Roberta , Antonacci Filippo , Carnevale Sergio , Sarotto Ivana , Dore Roberto , Filippi Andrea Riccardo , Chiara Gabriele , Regge Daniele , Preda Lorenzo , Morbini Patrizia , Stella Giulia Maria
Published: February 2020

Background

Few data are known regarding the molecular features and patterns of growth and presentation which characterize those lung neoplastic lesions presenting as non-solid nodules (NSN).

Methods

We retrospectively reviewed two different cohorts of NSNs detected by CT scan which, after transthoracic fine-needle aspiration (FNA) and core needle biopsy (CNB) received a final diagnosis of malignancy. All the enrolled patients were then addressed to surgical removal of lung cancer nodules or to exclusive radiotherapy. Exhaustive clinical and radiological features were available for each case.

Results

In all 62 analysed cases the diagnosis of adenocarcinoma (ADC) was reached. In cytologic samples, EGFR activating mutations were identified in 2 of the 28 cases (7%); no case showed ALK/EML4 or ROS1 translocations. In the histologic samples EGFR activating mutation were found in 4 out of 25 cases (16%). PD-L1 immunostains could be evaluated in 30 cytologic samples, while the remaining 7 did not reach the cellularity threshold for evaluation. TPS was < 1% in 26 cases,  > 1% < 50% in 3, and > 50% in 1. All surgical samples showed TPS < 1%. Of the 17 cases that could be evaluated on both samples, 15 were concordantly TPS 0, and 2 showed TPS > 1% < 50 on the biopsy samples. TPS was < 1% in 14 cases, > 1%/< 5% in 4 cases, > 5%/< 50% in 2 cases, > 50% in 1 case.

Conclusions

Overall PD-L1 immunostaining documented the predominance of low/negative TPS, with high concordance in FNA and corresponding surgical samples. It can be hypothesized that lung ADC with NSN pattern and predominant in situ (i.e. lepidic) components represent the first steps in tumor progression, which have not yet triggered immune response, and/or have not accumulated a significant rate of mutations and neoantigen production, or that they belong to the infiltrated-excluded category of tumors. The negative prediction of response to immunomodulating therapy underlines the importance of rapid surgical treatment of these lesions. Notably, cell block cytology seems to fail in detecting EGFR mutations, thus suggesting that this kind of sampling technique should be not adequate in case of DNA direct sequencing.
Orofacial pain in juvenile idiopathic arthritis is associated with stress as well as psychosocial and functional limitations
Authors: Dimitrijevic Carlsson Alexandra , Wahlund Kerstin , Kindgren Erik , Skogh Thomas , Starkhammar Johansson Carin , Alstergren Per
Published: February 2020

Background

The aim of this study was to investigate relations between psychosocial factors, signs and symptoms of orofacial pain and jaw dysfunction in patients with juvenile idiopathic arthritis (JIA).

Methods

Forty-five patients with JIA (median age 12 years) and 16 healthy matched controls (median age 13 years) were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The subjects answered the DC/TMD questionnaires regarding psychosocial factors (pain intensity, pain–related disability, depression, stress, catastrophizing, pain locations and jaw function).

Results

JIA patients with orofacial pain had higher degree of stress, depression, catastrophizing and jaw dysfunction compared to subjects without. In turn, these factors were associated with orofacial pain intensity. Also, patients with orofacial pain had higher systemic inflammatory activity.

Conclusions

Orofacial pain in patients with JIA is associated with stress, psychological distress, jaw dysfunction and loss of daily living activities. Pain intensity seems to be the major pain aspect related to these factors. In addition, systemic inflammatory activity appears to be an important factor contributing to orofacial pain in JIA.
RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway
Authors: Hou Kun , Li Guichen , Zhao Jinchuan , Xu Baofeng , Zhang Yang , Yu Jinlu , Xu Kan
Published: February 2020

Background

Mesenchymal stem cells (MSCs) are suspected to exert neuroprotective effects in brain injury, in part through the secretion of extracellular vesicles like exosomes containing bioactive compounds. We now investigate the mechanism by which bone marrow MSCs (BMSCs)-derived exosomes harboring the small non-coding RNA miR-29b-3p protect against hypoxic-ischemic brain injury in rats.

Methods

We established a rat model of middle cerebral artery occlusion (MCAO) and primary cortical neuron or brain microvascular endothelial cell (BMEC) models of oxygen and glucose deprivation (OGD). Exosomes were isolated from the culture medium of BMSCs. We treated the MCAO rats with BMSC-derived exosomes in vivo, and likewise the OGD-treated neurons and BMECs in vitro. We then measured apoptosis- and angiogenesis-related features using TUNEL and CD31 immunohistochemical staining and in vitro Matrigel angiogenesis assays.

Results

The dual luciferase reporter gene assay showed that miR-29b-3p targeted the protein phosphatase and tensin homolog (PTEN). miR-29b-3p was downregulated and PTEN was upregulated in the brain of MCAO rats and in OGD-treated cultured neurons. MCAO rats and OGD-treated neurons showed promoted apoptosis and decreased angiogenesis, but overexpression of miR-29b-3p or silencing of PTEN could reverse these alterations. Furthermore, miR-29b-3p could negatively regulate PTEN and activate the Akt signaling pathway. BMSCs-derived exosomes also exerted protective effects against apoptosis of OGD neurons and cell apoptosis in the brain samples from MCAO rats, where we also observed promotion of angiogenesis.

Conclusion

BMSC-derived exosomal miR-29b-3p ameliorates ischemic brain injury by promoting angiogenesis and suppressing neuronal apoptosis, a finding which may be of great significance in the treatment of hypoxic-ischemic brain injury.
Genetic characterization of HIV-1 epidemic in Anhui Province, China
Authors: Zhang Dong , Wu Jianjun , Zhang Yu , Shen Yuelan , Dai Sheying , Wang Xiaolin , Xing Hui , Lin Jin , Han Jingwan , Li Jingyun , Qin Yizu , Liu Yongjian , Miao Lifeng , Su Bin , Li Hanping , Li Lin
Published: February 2020

Background

Anhui Province in China is facing a severe HIV epidemic with an increasing number of newly diagnosed cases.

Methods

In this study, HIV genetic characteristics in the province were investigated. Newly reported HIV-positive individuals from 15 districts of Anhui Province were enrolled and interviewed. Total viral RNA was extracted from plasma isolated from blood samples. We amplified and sequenced an HIV pol fragment of the 1062 bp. The sequences were used for determination of HIV subtypes and the presence of drug resistance mutations. Transmission networks were constructed to explore possible relationships. And all of assembled partial pol genes were submitted to the Stanford HIV Drug Resistance Database website to find the transmitted drug resistance.

Results

Partial pol gene sequences were obtained from 486 cases. The results showed that MSM was the most dominant transmission route (253, 52.06%), followed by heterosexual transmission (210, 43.21%) and blood-borne transmission (1, 0.21%). Many subtypes were identified, including CRF01_AE (226, 46.50%), CRF07_BC (151, 31.07%), subtype B (28, 5.76%), CRF08_BC (20, 4.12%), CRF55_01B (15, 3.09%), CRF68_01B (7, 1.44%), CRF67_01B (3, 0.62%), CRF57_BC (2, 0.41%), CRF59_01B (2, 0.41%), CRF79_0107 (2, 0.41%), subtype C (2, 0.41%), CRF64_BC (1, 0.21%), and circulating recombinant forms (URFs) (27, 5.55%). Four transmission subnetworks containing high transmission risk individuals (with degree ≥4) were identified based on CRF01_AE and CRF07_BC sequences, including two CRF01_AE transmission subnetworks constituted by elderly people with average ages of 67.9 and 61.5 years. Infection occurred most likely through heterosexual transmission, while the other two CRF07_BC transmission subnetworks consist mainly of MSMs with average ages of 31.73 and 34.15. The level of HIV-transmitted drug resistance is 3.09%.

Conclusions

The simultaneous spread of multiple HIV subtypes in Anhui province underscores that close surveillance of the local HIV epidemic is necessary. Furthermore, the elderly people were frequently involved, arguing for behaviour intervention in this specific population besides the MSM risk group.
A native chromatin immunoprecipitation (ChIP) protocol for studying histone modifications in strawberry fruits
Authors: Huang Xiaorong , Pan Qinwei , Lin Ying , Gu Tingting , Li Yi
Published: February 2020

Background

Covalent modifications of histones and histone variants have great influence on chromatin structure, which is involved in the transcriptional regulation of gene expression. Chromatin immunoprecipitation (ChIP) is a powerful tool for studying in vivo DNA-histone interactions. Strawberry is a model for Rosaceae and non-climacteric fruits, in which histone modifications have been implicated to affect fruit development and ripening. However, a validated ChIP method has not been reported in strawberry, probably due to its high levels of polysaccharides which affect the quality of prepared chromatin and the efficiency of immunoprecipitation.

Results

We describe a native chromatin immunoprecipitation (N-ChIP) protocol suitable for strawberry by optimizing the parameters for nuclei isolation, chromatin extraction, DNA fragmentation and validation analysis using quantitative real-time PCR (qRT-PCR). The qRT-PCR results show that both the active mark H3K36me3 and the silent mark H3K9me2 are efficiently immunoprecipitated for the enriched regions. Compared to X-ChIP (cross-linked chromatin followed by immunoprecipitation), our optimized N-ChIP procedure has a higher signal-to-noise ratio and a lower background for both the active and the silent histone modifications. Furthermore, high-throughput sequencing following N-ChIP demonstrates that nearly 90% of the enriched H3K9/K14ac peaks are overlapped between biological replicates, indicating its remarkable consistency and reproducibility.

Conclusions

An N-ChIP method suitable for the fleshy fruit tissues of woodland strawberryFragaria vescais described in this study. The efficiency and reproducibility of our optimized N-ChIP protocol are validated by both qRT-PCR and high-throughput sequencing. We conclude that N-ChIP is a more suitable method for strawberry fruit tissues relative to X-ChIP, which could be combined with high-throughput sequencing to investigate the impact of histone modifications in strawberry and potentially in other fruits with high content of polysaccharides.
Computerized clinical decision support system for diabetes in primary care does not improve quality of care: a cluster-randomized controlled trial
Authors: Heselmans Annemie , Delvaux Nicolas , Laenen Annouschka , Van de Velde Stijn , Ramaekers Dirk , Kunnamo Ilkka , Aertgeerts Bert
Published: February 2020

Background

The EBMeDS system is the computerized clinical decision support (CCDS) system of EBPNet, a national computerized point-of-care information service in Belgium. There is no clear evidence of more complex CCDS systems to manage chronic diseases in primary care practices (PCPs). The objective of this study was to assess the effectiveness of EBMeDS use in improving diabetes care.

Methods

A cluster-randomized trial with before-and-after measurements was performed in Belgian PCPs over 1 year, from May 2017 to May 2018. We randomly assigned 51 practices to either the intervention group (IG), to receive the EBMeDS system, or to the control group (CG), to receive usual care. Primary and secondary outcomes were the 1-year pre- to post-implementation change in HbA1c, LDL cholesterol, and systolic and diastolic blood pressure. Composite patient and process scores were calculated. A process evaluation was added to the analysis. Results were analyzed at 6 and 12 months. Linear mixed models and logistic regression models based on generalized estimating equations were used where appropriate.

Results

Of the 51 PCPs that were enrolled and randomly assigned (26 PCPs in the CG and 25 in the IG), 29 practices (3815 patients) were analyzed in the study: 2464 patients in the CG and 1351 patients in the IG. No change differences existed between groups in primary or secondary outcomes. Change difference between CG and IG after 1-year follow-up was − 0.09 (95% CI − 0.18; 0.01, p-value = 0.06) for HbA1c; 1.76 (95% CI − 0.46; 3.98, p-value = 0.12) for LDL cholesterol; and 0.13 (95% CI − 0.91; 1.16, p-value = 0.81) and 0.12 (95% CI − 1.25;1.49, p-value = 0.86) for systolic and diastolic blood pressure respectively. The odds ratio of the IG versus the CG for the probability of no worsening and improvement was 1.09 (95% CI 0.73; 1.63, p-value = 0.67) for the process composite score and 0.74 (95% CI 0.49; 1.12, p-value = 0.16) for the composite patient score. All but one physician was satisfied with the EBMeDS system.

Conclusions

The CCDS system EBMeDS did not improve diabetes care in Belgian primary care. The lack of improvement was mainly caused by imperfections in the organizational context of Belgian primary care for chronic disease management and shortcomings in the system requirements for the correct use of the EBMeDS system (e.g., complete structured records). These shortcomings probably caused low-use rates of the system.

Trial registration

ClinicalTrials.gov, NCT01830569, Registered 12 April 2013.
Neurofibromatosis 1 French national guidelines based on an extensive literature review since 1966
Authors:   NF France Network, Bergqvist Christina , Servy Amandine , Valeyrie-Allanore Laurence , Ferkal Salah , Combemale Patrick , Wolkenstein Pierre
Published: February 2020

Neurofibromatosis type 1 is a relatively common genetic disease, with a prevalence ranging between 1/3000 and 1/6000 people worldwide. The disease affects multiple systems with cutaneous, neurologic, and orthopedic as major manifestations which lead to significant morbidity or mortality. Indeed, NF1 patients are at an increased risk of malignancy and have a life expectancy about 10–15 years shorter than the general population. The mainstay of management of NF1 is a patient-centered longitudinal care with age-specific monitoring of clinical manifestations, aiming at the early recognition and symptomatic treatment of complications as they occur. Protocole national de diagnostic et de soins (PNDS) are mandatory French clinical practice guidelines for rare diseases required by the French national plan for rare diseases. Their purpose is to provide health care professionals with guidance regarding the optimal diagnostic and therapeutic management of patients affected with a rare disease; and thus, harmonizing their management nationwide. PNDS are usually developed through a critical literature review and a multidisciplinary expert consensus. The purpose of this article is to present the French guidelines on NF1, making them even more available to the international medical community. We further dwelled on the emerging new evidence that might have therapeutic potential or a strong impact on NF1 management in the coming feature. Given the complexity of the disease, the management of children and adults with NF1 entails the full complement healthcare providers and communication among the various specialties.
Reduced chronic restraint stress in mice overexpressing hyperactive proteasomes in the forebrain
Authors: Kim Ji Hyeon , Kim Ahbin , Yun Yejin , Park Seoyoung , Lee Jung Hoon , Lee Yong-Seok , Lee Min Jae
Published: February 2020

While chronic restraint stress (CRS) results in depression-like behaviors possibly through oxidative stress in the brain, its molecular etiology and the development of therapeutic strategies remain elusive. Since oxidized proteins can be targeted by the ubiquitin-proteasome system, we investigated whether increased proteasome activity might affect the stress response in mice. Transgenic mice, expressing the N-terminally deleted version of α3 subunit (α3ΔN) of the proteasome, which has been shown to generate open-gated mutant proteasomes, in the forebrain were viable and fertile, but showed higher proteasome activity. After being challenged with CRS for 14 d, the mutant mice with hyperactive proteasomes showed significantly less immobility time in the forced swimming test compared with their wild-type littermates, suggesting that the α3ΔN transgenic mice are resistant to CRS. The accumulation of ER stress markers, such as polyubiquitin conjugates and phospho-IRE1α, was also significantly delayed in the hippocampus of the mutants. Notably, α3ΔN mice exhibited little deficits in other behavioral tasks, suggesting that stress resilience is likely due to the degradation of misfolded proteins by the open-gated proteasomes. These data strongly indicate that not only is the proteasome a critical modulator of stress response in vivo but also a possible therapeutic target for reducing chronic stress.
KDM4B facilitates colorectal cancer growth and glucose metabolism by stimulating TRAF6-mediated AKT activation
Authors: Li Haijie , Lan Jingqin , Wang Guihua , Guo Kaixuan , Han Caishun , Li Xiaolan , Hu Junbo , Cao Zhixin , Luo Xuelai
Published: February 2020

Background

Histone lysine demethylase 4B (KDM4B) has been implicated in various pathological processes and human diseases. Glucose metabolism is the main pattern of energy supply in cells and its dysfunction is closely related to tumorigenesis. Recent study shows that KDM4B protects against obesity and metabolic dysfunction. We realized the significant role of KDM4B in metabolism. However, the role of KDM4B in glucose metabolism remains unclear. Here, we sought to delineate the role and mechanism of KDM4B in glucose metabolism in colorectal cancer (CRC).

Methods

We first analyzed the role of KDM4B in glucose uptake and CRC growth. We then investigated the consequences of KDM4B inhibition on the expression of GLUT1 and AKT signaling, also explored the underlying mechanism. Finally, we detected the mechanism in vivo and assessed the potential correlation between the expression of KDM4B and CRC prognosis.

Results

We found that KDM4B promoted glucose uptake and ATP production by regulating the expression of GLUT1 via the AKT signaling pathway. KDM4B could interact with TRAF6 and promote TRAF6-mediated ubiquitination of AKT for AKT activation. Furthermore, we demonstrated that KDM4B was overexpressed in CRC specimens and high level of KDM4B was associated with a poor survival rate in CRC patients.

Conclusions

These findings reveal that KDM4B plays an important role in promoting CRC progression by enhancing glucose metabolism.
Real-time shear wave ultrasound elastography: a new tool for the evaluation of diaphragm and limb muscle stiffness in critically ill patients
Authors: Flatres Aurelien , Aarab Yassir , Nougaret Stephanie , Garnier Fanny , Larcher Romaric , Amalric Mathieu , Klouche Kada , Etienne Pascal , Subra Gilles , Jaber Samir , Molinari Nicolas , Matecki Stefan , Jung Boris
Published: February 2020

Background

Muscle weakness following critical illness is the consequence of loss of muscle mass and alteration of muscle quality. It is associated with long-term disability. Ultrasonography is a reliable tool to quantify muscle mass, but studies that evaluate muscle quality at the critically ill bedside are lacking. Shear wave ultrasound elastography (SWE) provides spatial representation of soft tissue stiffness and measures of muscle quality. The reliability and reproducibility of SWE in critically ill patients has never been evaluated.

Methods

Two operators tested in healthy controls and in critically ill patients the intra- and inter-operator reliability of the SWE using transversal and longitudinal views of the diaphragm and limb muscles. Reliability was calculated using the intra-class correlation coefficient and a bootstrap sampling method assessed their consistency.

Results

We collected 560 images. Longitudinal views of the diaphragm (ICC 0.83 [0.50–0.94]), the biceps brachii (ICC 0.88 [0.67–0.96]) and the rectus femoris (ICC 0.76 [0.34–0.91]) were the most reliable views in a training set of healthy controls. Intra-class correlation coefficient for inter-operator reproducibility and intra-operator reliability was above 0.9 for all muscles in a validation set of healthy controls. In critically ill patients, inter-operator reproducibility and intra-operator 1 and 2 reliability ICCs were respectively 0.92 [0.71–0.98], 0.93 [0.82–0.98] and 0.92 [0.81–0.98] for the diaphragm; 0.96 [0.86–0.99], 0.98 [0.94–0.99] and 0.99 [0.96–1] for the biceps brachii and 0.91 [0.51–0.98], 0.97 [0.93–0.99] and 0.99 [0.97–1] for the rectus femoris. The probability to reach intra-class correlation coefficient greater than 0.8 in a 10,000 bootstrap sampling for inter-operator reproducibility was respectively 81%, 84% and 78% for the diaphragm, the biceps brachii and the rectus femoris respectively.

Conclusions

SWE is a reliable technique to evaluate limb muscles and the diaphragm in both healthy controls and in critically ill patients.

Trial registration

The study was registered (ClinicalTrial NCT03550222).