bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of iron on the growth, biofilm formation and virulence of Klebsiella pneumoniae causing liver abscess
Authors: Chen Tao , Dong Guofeng , Zhang Siqin , Zhang Xiucai , Zhao Yajie , Cao Jianming , Zhou Tieli , Wu Qing
Published: February 2020

Background: Klebsiella pneumoniae is considered the most clinically relevant species of Enterobacteriaceae, known to cause severe infections including liver abscesses. To the best of our knowledge, a large proportion of iron in the human body is accumulated and stored in the liver. We hypothesize that increased iron availability is an important factor driving liver abscess formation and we therefore aim to understand the effects of iron on K. pneumoniae causing liver abscesses.

Results: All tested K. pneumoniae clinical isolates, including those isolated from liver abscesses and other abdominal invasive infection sites, grew optimally when cultured in LB broth supplemented with 50 μM iron and exhibited the strongest biofilm formation ability under those conditions. Decreased growth and biofilm formation ability were observed in all tested strains when cultured with an iron chelator (P<0.05). The infection model of G. mellonella larvae indicated the virulence of liver abscess-causing K. pneumoniae (2/3) cultured in LB broth with additional iron was significantly higher than those under iron-restricted conditions (P<0.05). The relative expression levels of the four siderophore genes (iucB, iroB, irp1, entB) in K. pneumoniae strains isolated from liver abscesses cultured with additional iron were lower than those under iron-restricted conditions (P<0.05).

Conclusions: It is suggested by our research that iron in the environment can promote growth, biofilm formation and enhance virulence of K. pneumoniae causing liver abscesses. A lower expression of siderophore genes correlates with increased virulence of liver abscess-causing K. pneumoniae. Further deeper evaluation of these phenomena is warranted.
Genomic Nucleotide-Based Distance Analysis for Delimiting Old World Monkey Derived Herpes Simplex Virus Species.
Authors: Kolb Aaron W , Brandt Curtis R
Published: February 2020

Herpes simplex viruses form a genus within the alphaherpesvirus subfamily, with three identified viral species isolated from Old World monkeys (OWM); Macacine alphaherpesvirus 1 (herpes B), Cercopithecine alphaherpesvirus 2 (SA8), and Papiine alphaherpesvirus 2 (PaHV-2; herpes papio). Herpes B is endemic to macaques, while PaHV-2 and SA8 appear endemic to baboons. All three viruses are genetically and antigenically similar, with SA8 and PaHV-2 thought to be avirulent in humans, while herpes B is a biosafety level 4 pathogen. Recently, next-generation sequencing (NGS) has resulted in an increased number of published OWM herpes simplex genomes, allowing an encompassing phylogenetic analysis. In this study, phylogenetic networks, in conjunction with a genome-based genetic distance cutoff method were used to examine 27 OWM monkey herpes simplex isolates. Genome-based genetic distances were calculated, resulting in distances between Lion and Pig-tailed simplex viruses themselves, and versus herpes B core strains that were higher than those between PaHV-2 and SA8 (approximately 14% and 10% respectively). The species distance cutoff was determined to be 8.94%, with the method recovering separate species status for PaHV-2 and SA8 and showed that Lion and Pig-tailed simplex viruses (vs core herpes B strains) were well over the distance species cutoff. In conclusion, we propose designating Lion and Pig-tailed simplex viruses as separate, individual viral species, and that this may be the first identification of viral cryptic species.
Suppression of behavioral activity and hippocampal noradrenaline caused by surgical stress in type 2 diabetes model mice
Authors: Nishimura Momoka , Nomura Yuki , Egi Moritoki , Obata Norihiko , Tsunoda Makoto , Mizobuchi Satoshi
Published: February 2020

Background: There has been much discussion recently about the occurrence of neuropsychological complications during the perioperative period. Diabetes is known to be one of the metabolic risk factors. Although the number of patients with diabetes mellitus (DM) has been increasing, the pathophysiology of postoperative neuropsychological dysfunction in DM patients is still unclear. Recently, a deficiency of neurotransmitters, such as monoamines, was reported to be associated with mental disorders. Therefore, we investigated the effects of surgical stress on behavioral activity and hippocampal noradrenaline (NA) level in type 2 diabetes mellitus model (T2DM) mice. Methods: Eighty-four 6-week-old male C57BL/6J mice were divided into four groups (non-diabetes, non-diabetes with surgery, T2DM, and T2DM with surgery groups). T2DM mice were established by feeding a high-fat diet (HFD) for 8 weeks. At 14 weeks of age, fifteen mice in each group underwent a series of behavioral tests including an open field (OF) test, a novel object recognition (NOR) test and a light-dark (LD) test. In the surgery groups, open abdominal surgery with manipulation of the intestine was performed 24 hours before the behavioral tests as a surgical stress. Hippocampal noradrenaline (NA) concentration was examined in six mice in each group by high-performance liquid chromatography. The data were analyzed by the Mann-Whitney U test, and p values less than 0.05 were considered significant. Results: The T2DM group showed significantly increased explorative activity in the NOR test (P = 0.0016) and significantly increased frequency of transition in the LD test (P = 0.043) compared with those in the non-diabetic group before surgery. In T2DM mice, surgical stress resulted in decreased total distance in the OF test, decreased explorative activity in the NOR test, and decreased frequency of transition in the LD test (OF: P = 0.015, NOR: P = 0.009, LD: P = 0.007) and decreased hippocampal NA (P = 0.015), but such differences were not observed in the non-diabetic mice. Conclusions: Mice with T2DM induced by feeding an HFD showed increased behavioral activities, and surgical stress in T2DM mice caused postoperative hypoactivity and reduction of the hippocampal NA level.
Successful Control of an Extended-spectrum Beta-lactamase-producing Klebsiella pneumoniae ST307 Outbreak in a Neonatal Intensive Care Unit
Authors: Baek Eun-Hwa , Kim Se-Eun , Kim Sunjoo , Lee Seungjun , Cho Oh-Hyun , Hong Sun In , Shin Jeong Hwan , Hwang Inyeong
Published: February 2020

Background : In this study, we evaluated the genetic relatedness of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KPN) isolates from an outbreak in a neonatal intensive care unit in August 2017 using pulse-field gel electrophoresis (PFGE) and sequence typing, we implemented an active countermeasure to control this outbreak successfully.
Methods: The incidence of healthcare-associated ESBL-KPN bacteremia was evaluated before and after initiating enhanced infection control (IC) practices in January 2018. Surveillance cultures were set up and monitored for neonates, medical personnel, and NICU environmental samples. Molecular analyses, including pulse-field gel electrophoresis (PFGE), sequence typing, and ESBL genotyping, were performed for the isolated KPN strains.
Results: After implementing the enhanced IC procedures, the healthcare-associated bacteremia rate decreased from 6.0 to 0.0 per 1,000 patient-days. Samples from neonates (n = 11/15, 73.3%), medical personnel (n = 1/41, 2.4%), and medical devices and the environments (6/181, 3.3%) tested positive for ESBL-KPN in the surveillance cultures in December 2017. Active surveillance cultures revealed that 23 of 72 neonates who were screened (31.9%) were colonized with ESBL-KPN between January and March 2018. All the isolates demonstrated closely related PFGE patterns and were identified as ST307 strain carrying the CTX-M-15 gene.
Conclusions: Contaminated neonate environments and medical devices, as well as transmission by medical personnel, appeared to be the source of the outbreak of ESBL-KPN infection. We employed an enhanced IC strategy during January-March 2018 and successfully controlled the clonal outbreak of CTX-M-15-positive KPN. ST307 has emerged as an important bacteremia-causing pathogen in the NICU and should be carefully monitored.
Different effects of Wnt/β-catenin activation and PTH activation in adult and aged male mice metaphyseal fracture healing
Authors: Liu Daocheng , Qin Hao , Yang Jiazhi , Yang Lei , He Sihao , Chen Sixu , Bao Quanwei , Zhao Yufeng , zong zhaowen
Published: February 2020

Background: Fractures in older men are not uncommon and need to be healed as soon as possible to avoid related complications. Anti-osteoporotic drugs targeting Wnt/β-catenin and PTH (parathyroid hormone) to promote fracture healing have become an important direction in recent years.

Objective: Observe whether there is a difference in adult and aged situations by activating two signal paths.

Methods: A single cortical hole with a diameter of 0.6 mm was made in the femoral metaphysis of Catnblox(ex3) mice and wild-type mice. The fracture healing effects of CA(Wnt/β-catenin activation) and PTH (activated by PTH (1–34) injections) were assessed by X-ray and CT imaging on days 7, 14, and 21 after fracture. The mRNA levels of β-catenin, PTH1R(Parathyroid hormone 1 receptor), and RUNX2(Runt-related transcription factor 2) in the fracture defect area were detected using RT-PCR. Angiogenesis and osteoblasts were observed by immunohistochemistry and osteoclasts were observed by TRAP (Tartrate-resistant Acid Phosphatase).

Result: Adult CA mice and adult PTH mice showed slightly better fracture healing than adult wild-type (WT) mice, but there was no statistical difference. Aged CA mice showed better promotion of angiogenesis and osteoblasts and better fracture healing than aged PTH mice.

Conclusion: The application of Wnt/β-catenin signaling pathway drugs for fracture healing in elderly patients may bring better early effects than PTH signaling pathway drugs, but the long-term effects need to be observed.
Observational study for laryngeal mask anesthesia combined with nerve block in internal fixation for rib fractures
Authors: Cao Jun , Zhang Junfeng , Gao Xiaoyun , Zhang Xiaoli , Li Jing
Published: February 2020

Background: General anesthesia with endotracheal intubation always has been considered mandatory for rib fractures surgery. Recently, there has been interestng in nonintubated technique of LMA anesthesia for lung surgery. We developed a protocol with laryngeal mask(LMA) anesthesia combined with nerve block for rib fractures surgery, and performed it in several cases prospectively.
Methods: Twenty patients undergoing unilateral rib fractures surgery were enrolled. Thoracic paravertebral block(TPB) and/or erector spinae plane block(ESPB) were carried out before LMA anesthesia. The vital signs(HR, BP, SpO 2 ) and parameters of breath were gathered during the operation. The arterial blood gas analysis and chest film were performed preoperatively and on the next day after operation. All patients received postoperative continous analgesia pump contained with 500mg of tramadol and 16mg of lornoxicam after the operation, and intravenous 50mg flurbiprofen Bisindie in the ward. Postoperative nausea and vomiting(PONV) within 48 hours after surgery and NRS pain scoreat 6(T1), 12(T2), 24(T3) hours after surgery were assessed as well. We also recorded the incidence of perioperative reflux, aspiration and nerve block complications.
Results: Thirteen males and seven females(mean age 54 years) were enrolled in this trial. 6(30%) had a flail chest, 9(45%) had haemothorax, 2(10%) had pulmonary contusion. The vital signs and spontaneous breathing were kept stable. End-tidal carbon dioxide concentrations(EtCO 2 ) were in an acceptable range(no more than 63 mmHg in all cases). The mean value of postoperative PaO 2 was increased than that of preoperative PaO 2 (91.2±16.0 vs. 83.7±15.9 mmHg, P=0.004). The mean value of preoperative and postoperative PaCO 2 was(42.1±3.7 vs. 43.2±3.7mmHg, P=0.165) respectively. Postoperative NRS at T1, T2, T3 was (3±1, 2±2, 0) respectively. No one suffered from PONV. In addition, perioperative reflux, aspiration and nerve block complications didn't appear in all cases.
Conclusions: The technique of laryngeal mask anesthesia combined with nerve block was feasible in the internal fixation for rib fractures.
Through service providers’ eyes: health systems factors affecting implementation of tuberculosis control in Enugu State, South-eastern Nigeria
Authors: Ogbuabor Daniel Chukwuemeka
Published: February 2020

Background Well-functioning health systems are essential to achieving global and national tuberculosis (TB) control targets. This study examined health system factors affecting implementation of TB control programme from the perspectives of service providers. Methods The study was conducted in Enugu State, South-eastern Nigeria using qualitative, cross-sectional design involving 23 TB service providers (13 district TB supervisors and 10 facility TB focal persons). Data were collected through in-depth, semi-structured interviews using a health system dynamic framework and analysed thematically. Results Stewardship from National TB Control Programme (NTP) improved governance of TB control, but stewardship from local government was weak. Government spending on TB control was inadequate, whereas donors fund TB control. Poor human resources management practices hindered TB service delivery. TB service providers have poor capacity for data management because changes in recording and reporting tools were not matched with training of service providers. Drugs and other supplies to TB treatment centres were interrupted despite the use of a logistics agency. Poor integration of TB into general health services, weak laboratory capacity, withdrawal of subsidies to community volunteers and patent medicine vendors, poorly funded patient tracking systems, and ineffectual TB/HIV collaboration resulted in weak organisation of TB service delivery. Conclusion Health systems strengthening for TB control service must focus on effective oversight from NTP and local health system; predictable domestic resource mobilisation through budgets and social health insurance; training and incentives to attract and retain TB service providers; effective supply and TB drug management; and improvements in organization of service delivery.
Variation of rhizosphere bacterial community diversity in the desert ephemeral plant Ferula sinkiangensis across environmental gradients
Authors: Tao Zhang , Li Dang Han , Ke Wang Zhong , Hua Lv Xin , Li Zhuang
Published: February 2020

Background
Ferula sinkiangensis is a desert short-lived medicinal plant, and its number is rapidly decreasing. Rhizosphere microbial community plays an important role in regulating global biogeochemical cycle, plant growth and adaptability. However, the Ferula sinkiangensis bacterial community and the processes that drive its assembly remain unclear.
Results
In this study, based on Illumina HiSeq high-throughput sequencing, we explored the diversity, structure and composition of Ferula sinkiangensis rhizosphere bacterial communities at different slope positions (upper, middle and bottom) and soil depths (0-10 cm, 10-25 cm, 25-40 cm) and their correlation with soil physicochemical properties. Actinobacteria (22.7%), Proteobacteria (18.6%), Acidobacteria (14.0%), Gemmatimonadetes (10.1%), Cyanobacteria (7.9%), Bacteroidetes (6.9%), Planctomycetes (3.9%), Verrucomicrobia (3.5%), Firmicutes (3.4%) and Chloroflexi (3.2%) were the dominant bacterial phyla in Ferula sinkiangensis rhizosphere soil. Variance analysis showed that the diversity and abundance of rhizosphere bacterial community in Ferula sinkiangensis were significantly different at various slope positions and soil depths. Specifically, the diversity of bacterial community was significantly higher at the top than the bottom of the slope, and the diversity and richness of bacterial community were significantly greater in the 0-10cm than the 25-40cm soil layer. Linear discriminant effect size (LEfSe) analysis showed the specific phyla and genera of bacteria affected by slope position and soil depth. For example, Planctomycetes, Sphingomonas , Rubrobacter and Adhaeribacter by slope position and significant impact on soil depth. In addition, distance-based redundancy analysis (db-RDA) and variance analysis showed that soil physicochemical factors jointly explained 29.81% of variation in Ferula sinkiangensis rhizosphere bacterial community structure. There was a significant positive correlation between available phosphorus（AP）and the diversity of Ferula sinkiangensis rhizosphere bacterial community ( p < 0.01), whereas pH largely explained the variation of Ferula sinkiangensis rhizosphere bacterial community structure (5.58%, p < 0.01), followed by altitude (5.53%), total salt (TS, 5.21%) and total phosphorus (TP, 4.90%).
Conclusion
Our results revealed the heterogeneity and variation trends of Ferula sinkiangensis rhizosphere bacterial community diversity and abundance on a fine spatial scale (slope position and depth) and shed new light on the mechanisms of coevolution and interaction between Ferula sinkiangensis and their rhizosphere bacterial communities across environmental gradients.
Neuromonitoring of delirium with quantitative pupillometry In sedated mechanically ventilated critically ill patients
Authors: Favre Eva , Bernini Adriano , Morelli Paola , Pasquier Jerôme , Miroz John-Paul , Abed-Maillard Samia , Ben-Hamouda Nawfel , Oddo Mauro
Published: February 2020

Background. Intensive care unit (ICU) delirium is a frequent secondary neurological complication in critically ill patients undergoing prolonged mechanical ventilation. Quantitative pupillometry is an emerging modality for the neuromonitoring of primary acute brain injury, but its potential utility in patients at risk of ICU delirium is unknown.
Methods. This was an observational cohort study of medical-surgical ICU patients, without acute or known primary brain injury, who underwent sedation and mechanical ventilation for at least 48 hours. Starting at day 3, automated infrared pupillometry – blinded to ICU caregivers – was used for repeated measurement of the pupillary function, including quantitative pupillary light reflex (q-PLR, expressed as % pupil constriction to a standardized light stimulus) and constriction velocity (CV, mm/sec). The relationship between delirium, using the CAM-ICU score, and quantitative pupillary variables was examined.
Results. A total of 59/100 patients had ICU delirium, diagnosed at a median 8 (5-13) days from admission. Compared to non-delirious patients, subjects with ICU delirium had lower values of q-PLR (25 [19-31] vs. 20 [15-28] %) and CV (2.5 [1.7-2.8] vs. 1.7 [1.4-2.4] mm/sec) at day 3, and at all additional time-points tested ( p <0.05). After adjusting for the SOFA score and the cumulative dose of analgesia and sedation, lower q-PLR was associated with an increased risk of ICU delirium (OR 1.057 [1.007-1.113] at day 3; p =0.03).
Conclusions. Sustained abnormalities of quantitative pupillary variables at the early ICU phase correlate with delirium and precede clinical diagnosis by a median 5 days. These findings suggest a potential utility of quantitative pupillometry in sedated mechanically ventilated ICU patients at high risk of delirium.
Effect of the Place of Living on Mortality in Patients with Advanced Heart Failure
Authors: Munoz Miguel-Angel , Garcia Raquel , Navas Elena , Duran Julio , Val-Garcia José-Luis Del , Verdú-Rotellar Jose-Maria
Published: February 2020

BackgroundSocial and environmental factors in advanced heart failure (HF) patients may be crucial to cope with the end stages of the disease. This study analyzes health inequalities and mortality according to place of residence (rural vs urban) in HF patients at advanced stages of the disease.MethodsPopulation-based cohort study including 1148 adult patients with HF attended in 279 primary care centers. Patients were followed for at least one year after reaching New York Heart Association IV, between 2010 and 2014.Data came from primary care electronic medical records. Cox regression models were applied to determine the hazard ratios (HR) of mortality.ResultsMean age was 81.6 (SD 8.9) years, and 62% were women. Patients in rural areas were older, particularly women aged >74 years (p=0.036), and presented lower comorbidity. Mortality percentages were 59% and 51% among rural and urban patients, respectively (p=0.030). Urban patients living in the most socio-economically deprived neighborhoods presented the highest rate of health service utilization, particularly with primary care nurses (p-trend <0.001). Multivariate analyses confirmed that men (HR 1.60, 95% confidence interval (CI) 1.34-1.90), older patients (HR 1.05, 95% CI 1.04-1.06), Charlson comorbidity index (HR 1.16, 95% CI 1.11-1.22), and residing in rural areas (HR 1.35, 95% CI 1.09 to 1.67) was associated with higher mortality risk.ConclusionsLiving in rural areas determines an increased risk of mortality in patients at final stages of heart failure.
The Fluctuation of Regulatory T Cells during Pregnancy and Obstetrical Complications
Authors: Zhao Yuan-Yuan , Li Ning , Bao Hongchu , Sung Nayoung , Zhang Xiaolu , Chen Linjing , Chen Lei , Ma Ding , Zhu Ping , Wang Wenjuan
Published: February 2020

Background: Regulatory T cells (Tregs) are critical immunomodulators during pregnancy by preventing maternal T-cell activation against fetal cells. However, how characteristics of maternal Tregs vary during pregnancy is still unclear. We analyzed the proportion and phenotypic characteristics of peripheral blood Tregs in normal pregnant women, women with recurrent pregnancy loss (RPL) or gestational diabetes mellitus (GDM), and non-pregnant women.Methods: We investigated the proportion of CD4+ Tregs, CD8+ Tregs and the expression of PD-1, GITR, HLA-G and CTLA-4 on them in the peripheral blood of normal pregnancies during 1st (n = 28), 2nd (n = 43), and 3rd trimester (n = 33); In addition, we evaluated pregnancies in the 1st trimester complicated by RPL (n = 21), in the 2nd (n = 17) and 3rd trimester (n = 28) complicated by GDM. Non-pregnant women (n = 57) were also investigated using flow cytometry.Results: During normal pregnancy, the proportion of CD4+ Tregs in all trimester and CD8+ Tregs in 2nd and 3rd trimester were higher(P ＜ 0.05，respectively) compared with non-pregnancy women. Moreover, the proportion of CD4+ Tregs was higher in 2nd trimester compared to 1st and 3rd trimester (P ＜ 0.01) while the proportion of CD8+ Tregs was higher in 3rd trimester compared to 1st and 2nd trimester (P ＜ 0.05). Compared to non-pregnant studies, the proportion of GITR+/CD8+ Tregs and HLA-G+/CD8+ Tregs in all trimester were higher(P ＜ 0.05, respectively). Moreover, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs, PD-1+/CD8+ Tregs and CTLA-4+/CD8+ Tregs in 3rd trimester were significantly higher compared to 1st, 2nd trimester and non-pregnant group(P ＜ 0.05, respectively).In RPL and GDM groups, the proportions of CD4+ Tregs in all trimesters were decreased while the proportions of CD8+ Tregs in all trimesters were increased compared to normal pregnant group (P ＜ 0.05，respectively).In RPL group, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs and HLA-G+/CD4+ Tregs were decreased compared to 1st trimester normal pregnant group (P ＜ 0.05，respectively). In 2nd trimester GDM group, the proportion of HLA-G+/CD4+ Tregs were decreased compared to 2nd trimester normal pregnant group (P ＜ 0.05，respectively). In 3rd trimester GDM group, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs, PD-1+/CD8+ Tregs, GITR+/CD8+ Tregs and HLA-G+/CD8+Tregs were decreased compared to 3rd trimester normal pregnant group (P ＜ 0.05, respectively).Conclusions: The proportion of CD4+ Tregs and CD8+ Tregs increased during pregnancy, the proportions and subsets of CD4+ Tregs decreased and those of CD8+ Tregs increased in pregnancies complicated by RPL and GDM, indicating that regulatory T cells play a role in pregnancy maintenance, and the abnormal expression of Tregs might be related to the complicated pregnancy.
Combined lateral peripatellar and posteromedial approaches for Schatzker type IV tibial plateau fractures involving posteromedial plane: A prospective study.
Authors: Zhang Jun , Yin Bo , Zhao Jianmin , Li Yihan , Yin Peng , Guo Tao
Published: February 2020

Objective The objective of this study to evaluate prospectively the effectiveness of Schatzker type IV tibial plateau fractures involving posteromedial plane managed by combined lateral peripatellar and posteromedial approaches Materials and methods We analyzed 18 patients with Schatzker type IV tibial plateau fractures involving posteromedial plane. There were 12 males and 6 females with an average of 38.5 years (range, 25-60 years). The mechanism of injury included traffic accident in 15 patients and falling in 3 patients. The injured lower limbs were right in 11 patients and left in 7 patients. The mean time from injury to surgery was 6.78 days (range, 5-9 days). There were 8 patients with meniscus injuries in our study. ResultsThe mean operation time was 3.41 hours (range, 3-4 hours). The mean blood loss was 352.78 ml (range, 300-410 ml). All the injured meniscuses were repaired. All patients were followed up, and the average time of follow up was 16.61 months (range, 14-22 months). Bone union was achieved at a mean of 12 weeks (range, 10-14 weeks). The mean degree of knee extension was 1.11° (range, 0-5°), and the mean degree of knee flexion was 120.56°(range, 110-130°). The mean points of KSS were 83 (range, 74-89 points). According to the criteria of KSS, 14 patients had clinical outcomes rated as excellent and 4 patients were rated as good. Conclusion Our results suggested that Combined lateral peripatellar and posteromedial approaches in the treatment of Schatzker type IV tibial plateau fractures involving posteromedial plane acquired satisfying outcomes. It was good for repairing the injured meniscus through our approaches.
First report of Lihan Tick virus (Phlebovirus, Phenuiviridae) in ticks, Colombia
Authors: Lopez Yesica , Miranda Jorge , Mattar Salim , Gonzalez Marco , Rovnak Joel
Published: February 2020

Background: Tick-borne Phleboviruses (TBPVs) comprise human and animal viruses that can cause a variety of clinical syndromes ranging from self-limiting febrile illness to fatal haemorrhagic fevers.Objective: Detect Phlebovirus in ticks collected from domestic animals in Córdoba, Colombia.Methods: We collected 2,365 ticks from domestic animals in three municipalities of the Department of Cordoba, Colombia in 2016. Ticks were identified and pooled by species for RNA extraction. A nested real-time PCR with specific primers for Phlebovirus and a probe for Heartland virus (HRTV) were performed. Also, a conventional nested PCR, with the same specific primers was used to detect other Phleboviruses, with positive reactions indicated by an amplified cDNA fragment of approximately 244 bp determined by gel electrophoresis. These bands were gel-purified and sequenced by the Sanger method.Results: Using real-time RT-PCR, no positive results for HRTV were found. However, using conventional nested PCR 2.2% (5/229 pools) yielded a product of 244 bp. One positive sample was detected in a pool of Dermacentor nitens ticks collected from a horse, and the four remaining positive pools were from Rhipicephalus microplus collected from cattle. The five positive nucleotide sequences were identical to each other, with identities of 93% to 96% compared to a section of the L-segment of Lihan Tick virus, a Phlebovirus originally detected in R. microplus ticks in China. The strongest identity (96%-99%) was with Lihan Tick virus detected in R. microplus ticks from Brazil.Conclusions: This is the first report of viral detection in ticks in Colombia. We detected a Colombian strain of Lihan Tick virus. We recommend investigating possible disease associations with this tick-borne virus in Colombia.
Arginine deimimase expressed in vivo activates the mitochondrial apoptosis pathway through inhibiting cytosolic ferritin and inducing chromotin autophagy
Authors: Feng Qingyuan , Bian Xuzhao , Liu Xuan , Wang Ying , Zhou Huiting , Ma Xiaojing , Quan Chunju , Yao Yi , Zheng Zhongliang
Published: February 2020

BackgroundBased on its low toxicity, arginine starvation therapy has the potential to treat those malignant tumors that can’t be treated by surgery. Arginine deiminase (ADI) gene is indicated to be an idea cancer-suppressor gene. ADI expressed in vivo displays higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000)[1]. However, it is still unknown whether cytosolic ADI has the same function mechanism as ADI-PEG20 or other underlying mechanisms in cells.MethodsThe interaction of ADI and other protein factors was screened by yeast hybrid, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting ferritin light-chain domain (FTL) on mitochondria damage was evaluated by site-directed mutation and flow cytometry. The apoptosis pathway of mitochondria control was analyzed by Western Blot and real-time PCR. The effect of p53 expression on cancer cell death was assessed by siTP53 transfection. The chromatin autophagy was explored by immunofluorescent staining and Western Blot.ResultsADI expressed in vivo inhibited the activity of cytosolic ferritin through interacting with FTL. The inactive mutant of ADI still aroused the apoptosis of some cells through mitochondria damage. Arginine starvation also induced the expression increase of p53 and p53AIP1, which aggravate cellular mitochondria damage. Chromatin autophagy appeared at the later stage of arginine starvation. DNA damage came along with the whole process of arginine starvation. Histone 3 (H3) was found in autophagosomes, which implied that cancer cells try to utilize the arginine in histones to survive during arginine starvation.Conclusions: Mitochondria damage is the major mechanism for ADI expressed in vivo to induce cancer cell death. Chromatophagy accumulations not only drive cancer cell to utilize histone arginine but also speed up cancer cell death at the later time point of arginine starvation.
Distinct clinical and prognostic implication of IDH1/2 mutation and other most frequent mutations in large duct and small duct subtypes of intrahepatic cholangiocarcinoma
Authors: Ma Bingqi , Meng Huijuan , Tian Ye , Wang Yingying , Song Tianqiang , Zhang Ti , Wu Qiang , Cui Yunlong , Li Huikai , Zhang Wei , Li Qiang
Published: February 2020

Background and Objective: IDH1/2, BAP1, ARID1A and PBRM1 have been reported as the most frequent mutant genes in ICCs, and their relationships with clinicopathological features and prognosis were researched in this study.Methods: We collected clinical data of 130 ICC patients from January 2012 to December 2017. The IDH1/2 mutation and loss of BAP1, ARID1A and PBRM1 expressions were detected by DNA sequencing or IHC methods, and histological subtype of ICCs was determined by HE, Alcian blue and S100P staining.Results: IDH1/2 mutation was related to decreased TBIL (P=0.039), ferritin (P=0.000) and higher histological differentiation (P=0.024), and was associated with prolonged DFS (P=0.009) and a trend toward increased OS (P=0.126) in small duct type of ICCs. IHC result of MsMab-1 was generally consistent with DNA sequencing for IDH1/2 mutant in ICCs (κ= 0.691). Only BAP1 expression loss was correlated to prolonged DFS (P=0.031) and OS (P=0.041) in large duct type of ICCs.Conclusions: IDH1/2 mutation may be a favorable predictor and be related to iron metabolism in small duct type of ICCs. Furthermore, we suggest that the detection of IDH1/2 mutation is indispensable to determine targeted therapy in small duct of ICCs, while it is not necessary in large duct of ICCs. MsMab-1 was a relatively effective multi-specific antibody against IDH1/2 mutant in ICCs. BAP1 expression loss was related to an improved prognosis in large duct type of ICCs.
The Invasion Depth Measurement of Bladder Cancer based on MRI
Authors: liu yang , Zheng Haojie , Xu Xiaopan , Zhang Xi , Du Peng , Liang Jimin , Lu Hongbing
Published: February 2020

Background: Invasion depth is an important index for staging and clinical treatment strategy of bladder cancer (BCa). The aim of this study was to investigate the feasibility of segmenting the BCa region from bladder wall region on MRI, and quantitatively measuring the invasion depth of the tumor mass in bladder lumen for further clinical decision-making. This retrospective study involved 20 eligible patients with postoperatively pathologically-confirmed BCa. It was conducted in the following steps: (1) a total of 1159 features were extracted from each voxel of both the certain cancerous and wall tissues with the T2-weighted (T2W) MRI data; (2) the support vector machine (SVM)-based recursive feature elimination (RFE) method was implemented to first select an optimal feature subset, and then develop the classification model for the precise separation of the cancerous regions; (3) after excluding the cancerous region from the bladder wall, the three-dimensional bladder wall thickness (BWT) was calculated using Laplacian method, and the invasion depth of BCa was eventually defined by the subtraction of the minimum BWT of the cancerous region and the mean BWT other than the cancerous region. Results: The segmented results showed a promising accuracy, with the mean Dice similarity coefficient of 0.921. The “soft boundary” defined by the voxels with the probabilities between 0.1 and 0.9 could demonstrate the overlapped region of cancerous and wall tissues. The invasion depth calculated from proposed segmentation method was compared with that from manual segmentation, with a mean difference of 0.277 mm. Conclusion: The proposed strategy could accurately segment the BCa region, and, as the first attempt, realize the quantitative measurement of BCa invasion depth.
Rolling Press Enables Electrospun Fibers Based Binder-Free Electrodes with High Stability for Lithium Ion Batteries
Authors: Zhao Yun , Kang Yuqiong , Deng Changjian , Liu Xinyi , Liang Zheng , Li Tao , Hu Quan
Published: February 2020

With the demand for higher energy density and smaller size lithium-ion batteries (LIBs), the development of high specific capacity active materials and the reduction of the usage of inactive materials are the main directions. Herein, a universal method is developed for binder-free electrodes for excellent stable LIBs by rolling the electrospun membrane directly onto the commercial current collector. The rolling process only makes the fiber web denser without changing the fiber structure, and the fiber web still maintains a porous structure. This strategy significantly improves the structural stability of the membrane compared to the direct carbonized electrospun membrane. Moreover, this method is suitable for a variety of polymerizable adhesive polymers, and each polymer can be composited with different polymers, inorganic salts, etc. The electrode prepared by this method can be stably cycled for more than 2000 cycles at a current density of 2500 mA g-1. This study provides a cost-effective and versatile strategy to design the LIB electrode with high energy density and stability for experimental research and practical application.
Biomechanical comparison of tenodesis reconstruction for subtalar instability: a finite element analysis
Authors: Xu Can , Li Mingqing , Wang Chenggong , Liu Hua
Published: February 2020

Background: There are several types of tenodesis reconstruction designed for subtalar instability. However, no comprehensive comparison has been conducted among these procedures in terms of their correcting power so far. The objective of this study is to evaluate the biomechanical behaviors of 5 representative procedures through finite element analysis.Methods: A finite element model was established and validated based on one of our previous studies. The Pisani interosseous talocalcaneal ligament(ITCL) reconstruction, Schon cervical ligament(CL) reconstruction and Choisne calcaneofibular ligament(CFL)reconstruction were compared on a model with the CFL, ITCL and CL sectioned. The Schon triligamentous reconstruction and Mann triligamentous reconstruction were compared on a model with the CFL, ITCL and CL, as well as the anterior talofibular ligament (ATFL) sectioned. The inversion and external/internal rotation were quantified in different ankle positions with rotational moment.Results: For single ligament reconstruction, the Choisne CFL reconstruction provided the greatest degree of correction for subtalar instability, followed by the Schon CL reconstruction and then the Pisani ITCL reconstruction. For triligamentous reconstruction, the Mann procedure outperformed the Schon procedure in alleviating the subtalar instability.Conclusion: The finite element analysis showed that the Choisne CFL reconstruction and Mann triligamentous reconstruction provided the greatest degree of immediate postoperative subtalar stability. However, both procedures could not restore the biomechanical behaviors of the subtalar joint to normal. The long-term efficacy of these procedures warrants further investigation using a substantially larger sample of clinical cases.
Informal support for people with Alzheimer’s Disease and related dementias in rural Uganda: A qualitative study
Authors: Nankinga Pia Ngoma , Maling Samuel , Chemali Zeina , Wakida Edith , Obua Celestino , Okello Elialilia S
Published: February 2020

Background The generation of people getting older has become a public health concern worldwide. People aged 65 and above are the most at risk for Alzheimer’s disease which is associated with physical and behavioral changes. This nurtures informal support needs for people living with dementia where their families together with other community members are the core providers of day to day care for them in the rural setting. Despite global concern around this issue, information is still lacking on informal support delivered to these people with dementia. Objective Our study aimed at establishing the nature of informal support provided for people with dementia (PWDs) and its perceived usefulness in rural communities in South Western Uganda. Methods This was a qualitative study that adopted a descriptive design and conducted among 22 caregivers and 8 opinion leaders in rural communities of Kabale, Mbarara and Ibanda districts in South Western Uganda. The study included dementia caregivers who had been in that role for a period of at least six months and opinion leaders in the community. We excluded trained health workers. Results The study highlights important forms of informal support offered to PWDs such as support in activities of daily living, enabling access to medical attention, recovering misplaced items, provision of herbal remedy, informal counseling, and sourcing carers from other families to offer presence and support in the hope to impact positively on behavioral outbursts and the frustration of living with dementia. Conclusion The study revealed various forms of informal support that are available for PWDs in South Western Uganda and stressed the role of caregivers and the perceived usefulness of the care provided.
Youth unemployment and Mental Health: Prevalence and determinant factors of depression among unemployed young adults in Gedeo zone, Southern Ethiopia
Authors: Mokona Hirbaye , Yohannes Kalkidan , Ayano Getinet
Published: February 2020

Background: The high rate of unemployment among young adults (aged 18 to 30 years) is a public health concern. The risk of mental health problems like depression is higher among the unemployed than among the employed. However, little is known about the prevalence and determinants of depression among unemployed young adults in Ethiopia. Hence, this study is aimed to assess the prevalence and determinant factors of depression among unemployed young adults in Gedeo zone, Southern Ethiopia. Methods: Community based cross sectional study design was conducted among 1419 unemployed young adults in Gedeo zone, Southern Ethiopia from May to July, 2019. Systematic random sampling technique was used to select study participants. Data on socio-demographic characteristics of unemployed young adults was collected by using structured questionnaire and presence of depression was assessed by Patient Health Questionnaire-9 (PHQ-9). Data was coded and entered into Epi-Data version 3.1 and analyzed by SPSS version 20. A multivariable logistic regression analysis was carried out to identify factors associated with depression, and variables with p-values < 0.05 were considered as statistically significant. The strength of the association was presented by adjusted odds ratio with their 95% confidence interval. Result: The overall prevalence of depression among unemployed young adults in the present study was 30.9% (95% CI: 28.4%, 33.1%). Of the total study participants with depression, 249(17.5%) had mild depression, 158(11.1%) had moderate depression, and 32(2.3%) had severe depression. Being male (AOR=1.40, 95%CI: 1.10, 1.80), long duration of unemployment (≥1years) (AOR=1.56, 95%CI: 1.21, 1.99), low self-esteem (AOR=1.32, 95%CI: 1.03, 1.68), poor social support (AOR=1.98, 95%CI: 1.34, 2.93), and current alcohol use (AOR=1.86, 95%CI: 1.33, 2.59) were significantly associated with depression among unemployed young adults. Conclusion : Our study revealed a high prevalence of depression among unemployed young adults, with three out of ten unemployed young adults having significant depression. Being male, long duration of unemployment, low self-esteem, poor social support, and current alcohol use were statistically significant with depression. Therefore, our study suggest that Policy makers, program planners, and other concerned bodies should establish appropriate strategy for prevention, early detection and management of depression among unemployed young adults.
Immune checkpoint inhibitor-induced inflammatory arthritis: a qualitative study identifying unmet patient needs and care gaps
Authors: Cappelli Laura , Grieb Suzanne M. , Shah Ami A. , Bingham Clifton O. , Orbai Ana-Maria
Published: February 2020

ObjectivesPatients treated for cancer with immune checkpoint inhibitors (ICI) may develop autoimmune adverse events, including ICI-induced inflammatory arthritis (IA). ICI-induced IA treatment requires balancing immune activation to fight cancer and immune modulation to control autoimmunity. Our objective was to learn how patients experience ICI-induced IA and potentially conflicting treatment decisions. Methods Semi-structured interviews were conducted with participants with rheumatologist-diagnosed ICI-induced IA recruited from a longitudinal cohort. The interview guide probed the experience of diagnosis and treatment, symptoms and impact of ICI-induced IA, coping mechanisms, and treatment decision-making. Two researchers used an iterative coding process to identify themes through inductive thematic analysis and consensus. An overarching conceptual framework was derived from the qualitative analysis to identify care gaps perceived by patients, and inform future research. Results Fourteen patients with ICI-induced IA participated in semi-structured interviews. Five overarching themes were identified: an awareness gap leading to delay in diagnosis of IA, descriptors of ICI-induced IA and relationship to other adverse events, emotional and quality-of-life impact of IA, fear and decision-making, and contextual factors including social support. Conclusions As reported by patients, ICI-induced IA had a significant functional and emotional impact, even as compared to cancer and other ICI-induced side effects. Increasing awareness and integrated care of ICI-induced IA, and increasing social support are key targets for improving patient care. Additionally, more data on cancer outcomes in patients requiring immunomodulation for ICI-induced IA would help address fear and uncertainty for patients, and better support them through therapeutic decisions.
Assessment of a novel method to detect clarithromycin-resistant Helicobacter pylori using a stool antigen test reagent
Authors: Kakiuchi Toshihiko , Hashiguchi Kazutoshi , Imamura Ichiro , Nakayama Aiko , Takamori Ayako , Okuda Masumi , Matsuo Muneaki
Published: February 2020

Background The resistance rate of Helicobacter pylori to clarithromycin (CAM) is high among the infected children in Japan; therefore, a new method for detecting CAM-resistant H. pylori using a less invasive technique is strongly desired. We aimed to confirm the clinical usefulness of our newly developed Nested polymerase chain reaction-QProbe (quenching probe) (Nested PCR-QP) method using stool specimens. Methods The first was an evaluation of our method using the residual solution of the H. pylori stool antigen test for adolescents, and the second was an evaluation of our method using culture testing for adults. Results Of the 57 middle school students with H. pylori , the Nested PCR-QP test results of 53 (90.3%) could be analyzed; 28 students were found to have CAM resistance mutations. The results indicating genetic mutation in 28 and no mutation in 23 students were consistent with those of PCR-direct sequencing. In the 23 adults who were diagnosed with H. pylori infection using the rapid urease test and culture testing, it was possible to use Nested PCR-QP for analyzing all 21 adults who tested positive in the stool H. pylori antigen test. The results obtained for all the 21 adults were consistent with those obtained via the drug susceptibility test. Conclusions Our novel method could be useful for non-invasively detecting CAM resistance mutations in H. pylori. This may help select an eradication drug to reduce eradication failure rates against H. pylori.
A Chinese Case Series of Schnitzler Syndrome and Complete Remission in One Tocilizumab-treated Patient
Authors: Yan Ruyu , Shen Min , Cao Wei , Liu Xinchao , Li Feng
Published: February 2020

Backgroud: Schnitzler syndrome (SchS) is a rare acquired systemic autoinflammatory disease. The major clinical features of SchS are urticarial rash and monoclonal gammopathy, accompanied by fever, joint pain and lymphadenopathy. There were few reports about SchS in Chinese population. Herein, we describe two patients with SchS in China. Methods: Two Chinese Han patients were diagnosed as SchS in our department from 2017 to 2019. Their phenotype and genotype were carefully documented and studied. We also conducted a systematic literature review about SchS. Results: There were one man and one woman with an average disease-onset age of 52. Recurrent fever and urticarial rash occurred in both of them during the febrile attacks and normalized in asymptomatic intervals. Other manifestations included arthritis/arthralgia, lymphadenopathy and hearing loss. Hepatic cirrhosis and epilepsy were seen in one patient. None of them had bone pain or family histories. Serum monoclonal IgM gammopathy was found in both patients. MyD88 gene mutation L258P was identified in one patient. They were treated with tocilizumab and tripterygium wilfordii Hook F (TwHF) respectively and both showed good response. Conclusions: The rarity and diversity of SchS makes it difficult to be recognized. The patient in our study was the first SchS with concomitant liver and neural damage. Anti-IL-6 agents and TwHF may be alternative therapies when anti-IL-1 therapy is unresponsive or unavailable.