bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Albumin and Activities of Daily Living in Chinese Centenarians: A Cross-Sectional Study
Authors: Han Ke , Wang Shengshu , Jia Wangping , Cao Wenzhe , Liu Miao , Yang Shanshan , Wang Jianhua , He Yao
Published: January 2020

Background Objective deterioration in activities of daily living (ADL) exists in older people, particularly grows with age. While as the criterion standard of positive aging and longevity, little information that focuses on centenarians is available. The objective of this study is to examine the relationship between serum albumin and activities of daily living among centenarians in long-lived areas.Methods design—population-based cross-sectional study; setting—a complete sample study in Hainan, the longest-lived areas of China; subjects—Chinese older adults aged 100 and above (N=1002); measurements—serum albumin, basic and instrumental activities of daily living (BADL and IADL).Results Of 1002 participants included in the analysis 287(28.64%) were BADL disability, and 648(64.67%) were IADL disability. The median serum albumin level was 38.5 g/L (interquartile range, 36.2-41.3). In multivariable analyses controlling for socio-demographic characteristics, lifestyle characteristics and other influential factors, low albumin in the bottom quartile were associated with BADL disability (OR=5.994;95% CI: 3.542-10.143) and IADL disability (OR=4.398; 95% CI, 2.661-7.269). Serum albumin concentration showed a significant inverse linear relationship with ADL disability (P for trend <0.001). In sex-stratified analyses, the association was more pronounced in women. And we found a nonlinear relationship between serum albumin and IADL disability in female centenarians (P=0.025) from restricted cubic splines.Conclusions Low levels of albumin were associated with the decline in ADL function in centenarians, and this association was gender-specific and more prominent in the female.
Study Protocol Daiobotanpito combined with antibiotic therapy for treatment of acute diverticulitis: a study protocol for a randomized controlled trial
Authors: Ogawa-Ochiai Keiko , Yoshimura Keinichi , Shirai Akiko , Sakai Seisho , Moriyama Hideki , Nakamura Keishi , Murayama Toshinori , Ishikawa Hideki
Published: January 2020

Background: Colonic diverticular disease has been increasing in prevalence due to the rapidly aging global population, but standard treatment has not changed dramatically in recent years. Daiobotanpito (DBT; Da Huang Mu Dan Tang in Chinese) has been used in medical treatment of acute abdominal abscesses, such as appendicitis or diverticulitis in traditional Japanese (Kampo) medicine for many years, based on more than 3000 years of experience. Prior to this study, a retrospective open-label trial was conducted to compare patients with acute diverticulitis who received oral DBT combined with intravenous antibiotics with those who received intravenous antibiotic alone; it showed a positive effect of DBT on acute diverticulitis. We aim to investigate whether moderate to severe acute diverticulitis shows greater improvement with intravenous antibiotics plus orally administered DBT compared with intravenous antibiotics with placebo. Methods: This is a two-group, randomized, double-blind, placebo-controlled, multi-center trial, which is designed to evaluate the efficacy and safety of DBT for moderate to severe diverticulitis patients treated with intravenous antibiotics. Eligible participants will be randomized to either a treatment group receiving a 10-day oral DBT regimen plus conventional therapy or a control group receiving a 10-day placebo regimen plus conventional therapy. The primary outcome will be the treatment success rate of diverticulitis defined as fever relief to <37.5 ℃ within 3 days or/and elimination of abdominal pain within 4 days. Secondary endpoints will include hospitalization days, changes in inflammatory response (CRP, WBC, neutrophil count), thermal type, number of days before beginning food intake, recurrence rate (observation for 1 year after registration), and adverse event expression rate. Assessments will be performed at baseline and on the day of discharge. The recurrence rate will be recorded at 1 year after registration. Discussion: This study is expected to provide evidence to support the clinical benefits of DBT in the treatment of acute diverticulitis. It may also provide evidence regarding the efficacy and safety of DBT in the recurrence of acute diverticulitis. Trial registration: UMIN000027381, registered on April 27th, 2017 https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000031377, and changed to jRCTs041180063, registered on July 30th, 2019; https://jrct.niph.go.jp/en-latest-detail/jRCTs041180063 as a result of the revision of the domestic law in 2018 in Japan.
Molecular detection and phylogenetic analysis of Lumpy skin disease virus from outbreaks in Uganda 2017-2018
Authors: Ochwo Sylvester , VanderWaal Kimberly , Ndekezi Christian , Nkamwesiga Joseph , Munsey Anna , Witto Sarah Gift , Nantima Noelina , Mayanja Franklin , Okurut Anna Rose Ademun , Atuhaire David Kalenzi , Mwiine Frank Norbert
Published: January 2020

Background Lumpy skin disease (LSD) is an infectious viral disease of cattle caused by a capripox virus. LSD has substantial economic implications, with infection resulting in permanent damage to the skin of affected animals which lowers their commercial value. In Uganda, LSD is endemic and cases of the disease are frequently reported to government authorities. This study was undertaken to molecularly characterize lumpy skin disease virus (LSDV) strains that have been circulating in Uganda between 2017 and 2018. Secondly, the study aimed to determine the phylogenetic relatedness of Ugandan LSDV sequences with published sequences, available in GenBank.Results A total of 7 blood samples and 16 skin nodule biopsies were screened for LSDV using PCR to confirm presence of LSDV nucleic acid. PCR positive samples were then characterised by amplifying the GPCR gene. These amplified genes were sequenced and phylogenetic trees were constructed. Out of the 23 samples analysed, 15 were positive for LSDV by PCR (65.2%). The LSDV GPCR sequences analysed contained the unique signatures of LSDV (A11, T12, T34, S99, and P199) which further confirmed their identity. Sequence comparison with vaccine strains revealed a 12bp deletion unique to Ugandan outbreak strains. Phylogenetic analysis indicated that the LSDV sequences from this study clustered closely with sequences from neighboring East African countries and with LSDV strains from recent outbreaks in Europe. It was noted that the sequence diversity amongst LSDV strains from Africa was higher than diversity from Eurasia.Conclusion The LSDV strains circulating in Uganda were closely related with sequences from neighboring countries. Comparison of GPCR gene showed that vaccine strains were not responsible for outbreaks. This means that vaccination with the currently used vaccine will probably be effective for the control of LSD in Uganda. This information is necessary to understand LSDV molecular epidemiology and to contribute knowledge towards the development of more appropriate control strategies by the Government of Uganda.
In vitro and in situ study on characterizationand mechanismofthe intestinal absorptionof 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside
Authors: Wang Cheng , Zhou Yimeng , Gong Xiaohong , Zheng Li , Li Yunxia
Published: January 2020

Background: 2,3,5,4'-tetrahydroxystilbence-2-O-β-D-glucoside(TSG) is a polyhydroxyphenolic compound, which exhibited a broad spectrum of pharmacological activities, such asanti-inflammatory, anti-depression, anti-oxidation and anti-atherosclerosis.However, the compound had poor bioavailability and the underlying absorption mechanisms had not been studied. Therefore, the purpose of this study was to investigate the intestinal absorption mechanism of TSG. Methods: This study used Caco-2 cell monolayer model and single-passintestinal perfusion modelto explore the gastrointestinal absorption mechanisms of TSG. The effects of basic parameters such as drug concentration, time and pH on the intestinal absorption of TSG were analyzed by high performance liquid chromatography.The absorption susceptibility of TSG to three inhibitors, P-gp inhibitors verapamil hydrochloride and quinidine, and MRP2 inhibitor probenecid were also assessed. Results: TSG was poorly absorbed in the intestines and the absorption of TSG in stomach is much higher than that in intestine. Both in vitro and in situ experiments showed that the absorption of TSG was saturated with increasing concentration and it was better absorbed in a weakly acidic environment pH 6.4. Moreover, TSG interacts with P-gp and MRP2, and TSG was not only the substrate of the P-gp and MRP2, but also affected the expression of P-gp and MRP2. Conclusions: It wasconcluded that the gastrointestinalabsorption mechanisms ofTSG involved processes passive transport and the participation ofefflux transporters.
An integrated intervention for chronic care management in rural Nepal: a protocol of a type 2 hybrid effectiveness-implementation study
Authors: Schwarz Dan , Dhungana Santosh , Kumar Anirudh , Acharya Bibhav , Agrawal Pawan , Aryal Anu , Baum Aaron , Choudhury Nandini , Citrin David , Dangal Binod , Dhimal Meghnath , Gauchan Bikash , Gupta Tula , Halliday Scott , Karmacharya Biraj , Kishore Sandeep , Koirala Bhagawan , Kshatriya Uday , Levine Erica , Maru Sheela , Rimal Pragya , Sapkota Sabitri , Schwarz Ryan , Shrestha Archana , Thapa Aradhana , Maru Duncan
Published: January 2020

Background In Nepal, the burden of non-communicable, chronic diseases is rapidly rising, and disproportionately affecting low- and middle-income countries. Integrated interventions are essential in strengthening primary care systems and addressing the burden of multiple comorbidities. A growing body of literature supports the involvement of frontline providers, namely mid-level practitioners and community health workers, in chronic care management. Important operational questions remain, however, around the digital, training, and supervisory structures to support the implementation of effective, affordable, and equitable chronic care management programs. Methods A twelve-month, population-level, type 2 hybrid effectiveness-implementation study will be conducted in rural Nepal to evaluate an integrated non-communicable disease care management intervention within Nepal’s new municipal governance structure. The intervention will leverage the government’s planned roll-out of the World Health Organization’s Package of Essential Non-communicable disease interventions (WHO-PEN) program in four municipalities in Nepal, with a study population of 80,000. The intervention will leverage both the WHO-PEN and its cardiovascular disease specific technical guidelines, HEARTS, and include three evidence-based components: 1) non-communicable disease care provision using mid-level practitioners and community health workers; 2) digital clinical decision support tools to ensure delivery of evidence-based care; and 3) training and digitally-supported supervision of mid-level practitioners to provide motivational interviewing for modifiable risk factor optimization, with a focus on medication adherence, and tobacco and alcohol use. The study will evaluate effectiveness using a pre-post design with stepped implementation. The primary outcomes will be disease-specific, “at-goal” metrics of chronic care management; secondary outcomes will include alcohol and tobacco consumption levels. Discussion This is the first population-level, hybrid effectiveness-implementation study of an integrated chronic care management intervention in Nepal. As low- and middle-income countries plan for the Sustainable Development Goals and universal health coverage, the results of this pragmatic study will offer insights into policy and programmatic design for non-communicable disease care management in the future.
M1 Macrophage Infiltrations Exacerbate Muscle and Bone Atrophy after Peripheral Nerve Injury
Authors: Shimada Nobuhiro , Sakata Asuka , Igarashi Takashi , Takeuchi Mamoru , Nishimura Satoshi
Published: January 2020

Background: Peripheral nerve injury causes limb muscle/bone atrophy, leading to chronic pain. However, the mechanisms underlying muscle/bone atrophy after peripheral nerve injury remain unknown. It was recently reported that M1 macrophages are the main factors responsible for neurogenic inflammation after peripheral nerve injury. We hypothesized that M1 macrophages are important in muscle/bone atrophy after nerve injury. Therefore, we investigated the influence of M1 macrophages on muscle/bone atrophy after nerve injury in mice to prevent muscle/bone atrophy by suppressing M1 macrophages.

Methods: Hindlimb muscle weight and total bone density were measured in a chronic constriction injury (CCI) mouse model. Immunohistochemical analysis and intravital microscopy were performed to visualize hindlimb muscles/bones, and cells were quantified using flow cytometry. We compared M1 macrophage infiltration into muscles/bones and muscle/bone atrophy between macrophage depletion and untreated groups. We also investigated muscle/bone atrophy using administration models for anti-inflammatory and neuropathic pain drugs.

Results: Peripheral nerve injury caused significant reduction in muscle weight and total bone density at 1 and 3 weeks after CCI, respectively, compared with that in controls. Osteoclast numbers were significantly higher at 1 week after CCI in the CCI group than in the control group. M1 macrophage infiltration into muscles was observed from 2 hours after CCI via intravital microscopy and 1 week after CCI, and it was significantly higher 1 week after CCI than in the control group. In the macrophage depletion group, dexamethasone, pregabalin, and loxoprofen groups, M1 macrophage infiltration into muscles/bones was significantly lower and muscle weight and total bone density were significantly higher than in the untreated group.

Conclusions: M1 macrophage infiltration exacerbates muscle/bone atrophy after peripheral nerve injury. By suppressing M1 macrophages at the neural injury local site, muscle/bone atrophy could be avoided.
A Randomized Double-Blind Comparison of the Double-Space Technique versus the Single-Space Technique in Combined Spinal-Epidural Anesthesia for Cesarean Section
Authors: Chun Eun Hee , Cho Sooyoung , Woo Jae Hee , Kim Youn Jin
Published: January 2020

Background: Combined spinal-epidural anesthesia (CSEA) can be performed with either a single-space technique or a double-space technique for cesarean section. We performed a double-blind randomized controlled study to compare the effect of the double-space technique with that of the single-space technique on sensory block level and side effects.

Methods: Parturients undergoing elective cesarean section under regional anesthesia were randomized to receive CSEA with either the double-space technique (double group, n = 20) or the single-space technique (single group, n = 20). In the double group, an epidural catheter was inserted at the L1–2 interspace, and dural puncture was performed at the L3–4 interspace. In the single group, the procedure was performed at the L3–4 interspace using the needle-through-needle technique.

Results: There were no differences in time to readiness or intraoperative level of sensory block between the two groups. The postoperative sensory level was maintained at a higher level in the double group than in the single group (1 h postoperatively, P = 0.029; 6 h postoperatively, P = 0.016). There was no difference between the two groups in terms of side effects. The parturient satisfaction scores 48 h postoperatively were significantly different between groups (9.5 in the double group vs. 8 in the single group, P = 0.004).

Conclusions: We conclude that there were no differences in intraoperative variables between the double-space technique and the single-space technique for CSEA. However, double-space CSEA for cesarean section may be beneficial for controlling postoperative pain and improving parturient satisfaction.

Trial registration: The study was retrospectively registered at https://cris.nih.go.kr under the trial ID KCT0002514. Date of registration: October 27, 2017.
Effectiveness and feasibility of Heavy Slow Resistance Training in patients with subacromial shoulder pain. A single-blind, randomized pilot study.
Authors: Kvalvaag Elisabeth , Høiland Hans Hugo Fredriksen , Johnsen Marianne Bakke , Brox Jens Ivar , Engebretsen Kaia Beck , Røe Cecilie
Published: January 2020

Background Subacromial shoulder pain is the most common shoulder diagnosis, and should preferably be treated non-operatively. Previous studies have shown promising results of Heavy Slow Resistance training (HSR) in patellar and Achilles tendinopathy, but few studies have evaluated the effect of HSR for shoulder pain. The purpose of this pilot trial was to evaluate if HSR training is feasible for patients with subacromial shoulder pain, and to compare the effect of HSR to traditional supervised exercises on pain and function of the shoulder. Methods Twenty-two patients with subacromial shoulder pain lasting at least three months were recruited and randomized to HSR (n=11) or traditional supervised exercises (n=11) by computer-generated randomization in blocks of four. Patients received HSR once a week, in addition to home-training twice a week, or supervised exercises twice a week for 12 weeks, in addition to daily home-training. The primary outcome measure was the Shoulder Pain and Disability Index (SPADI). Linear regression analysis was applied to evaluate the between group differences after 12 weeks. Outcome assessors were masked.Results After 12 weeks, patients in both groups had improved significantly from baseline in SPADI score (P=0.001) but no group difference was found (mean difference 1.3; 95% CI, -21.9 to 24.5, P=0.91). Similar non-significant results between groups were seen for pain in activity and rest, and the DASH score. Conclusion This pilot-study observed no difference in effectiveness of HSR compared to supervised exercises for patients with subacromial shoulder pain and both groups improved significantly from baseline. Based on this, HSR appears to be as feasible and effective as supervised exercises for this patient group, but studies with larger sample size is required.
Influence of genetic polymorphisms in homocysteine and lipid metabolism systems on antidepressant drug response
Authors: Yuan Baoyu , Sun Xiaoyan , Xu Zhi , Pu Mengjia , Yuan Yonggui , Zhang Zhijun
Published: January 2020

Background Chronic lesions of small blood vessels and capillaries may play a role in the pathogenesis of depression. As the genes associated with these vascular risk factors may be involved in depression, these genetic polymorphisms may affect the efficacy of antidepressants. This study was performed to investigate the roles of methylenetetrahydrofolate reductase (MTHFR), apolipoprotein E (ApoE), and apolipoprotein A4 (ApoA4) genetic polymorphisms in antidepressant response in depressive patients.Methods A total of 281 Han Chinese patients received a single antidepressant drug for at least 6 weeks. The Hamilton Depression Rating Scale (HAMD-17) was used to evaluate the severity of depressive symptoms and the therapeutic effects of the drug administered. Eight single nucleotide polymorphisms (SNPs) of MTHFR, ApoE, and ApoA4 genes were detected using gene chips. Differences in clinical variables between the responders and non-responders, as well as between remission and non-remission groups, were examined using the independent samples t test and Pearson’s χ 2 test. In addition, the associations of single loci and haplotypes with treatment response were analyzed.Results Among the eight SNPs in four genes, two SNPs (ApoA4 rs5101 and rs675) were eliminated as they had a MAF < 5%.Haplotype(C-A) in MTHFR (rsl801133 and rs1801131) was significantly associated with better antidepressant response in the 8-week antidepressant group overall ( P = 0.0007), and in the male subgroup ( P = 0.003), and serotonin norepinephrine reuptake inhibitor (SNRI) subgroup ( P = 0.001). The ApoE rs405509 C allele was significantly associated with poorer antidepressant response in the 6-week male subgroup ( P = 0.004), while the 405509 AA genotype was associated with better antidepressant efficacy in the 6-week antidepressant group overall ( P = 0.006) and male subgroup ( P = 0.002).Conclusions Genetic polymorphisms of MTHFR, ApoE, and ApoA4 may be associated with the efficacy of antidepressants, in which the haplotype (rs1801131-rs1801133) A–C type was associated with better antidepressant efficacy, especially in males and in patients using SNRIs. The efficacy of antidepressants may be better in ApoE rs405509 A allele and AA genotype carriers, but worse in ApoA4 rs5092 G allele and GG genotype carriers.
Validity and Item Response Theory Properties of the Patient Health Questionnaire-9 for Primary Care Depression Screening in Mozambique (PHQ-9-MZ)
Authors: Cumbe Vasco Francisco Japissane , Muanido Alberto Gabriel , Manaca Maria Nélia , Fumo Hélder , Chiruca Pedro , Hicks Leecreesha , Mari Jair de Jesus , Wagenaar Bradley H
Published: January 2020

Background: Depression is one of the leading causes of disability in Mozambique; however, few patients with depression are identified in primary care. To our knowledge, there are no validated tools for depression screening in Mozambique. The aim of this study was to validate the Patient Health Questionnaire-9 (PHQ-9) for use in primary care settings in Mozambique.
Methods: The PHQ-9 was adapted using a structured multi-phase process led by a team of bilingual experts followed by a review by lay individuals and pilot-testing including cognitive interviews. The final Mozambican PHQ-9 (PHQ-9-MZ) was applied among 503 individuals randomly selected from antenatal, postpartum, and general outpatient consultations in three Ministry of Health primary healthcare clinics in Sofala Province, Mozambique. The PHQ-9-MZ was evaluated against the MINI 5.0-MZ as a gold standard diagnostic tool.
Results: The majority of participants were female (74%), with a mean age of 28. Using the MINI 5.0-MZ, 43 (9%) of the sample tested positive for major depressive disorder. Items of the PHQ-9-MZ showed good discrimination and factor loadings. One latent factor of depression explained 54% of the variance in scores. Questions 3 (sleep) and 5 (appetite) had the lowest item discrimination and factor loadings. The PHQ-9-MZ showed good internal consistency, with a Cronbach’s alpha of 0.84, and an area under the receiver operating characteristic curve (AUROC) of 0.81 (95% CI: 0.73, 0.89). The PHQ-2-MZ had an AUROC of 0.78 (95% CI: 0.70, 0.85). Using a cut-point of ≥9, the PHQ-9-MZ had a sensitivity of 46.5% and a specificity of 93.5%. Using a cut-point of ≥2, the PHQ-2-MZ had a sensitivity of 74.4% and a specificity of 71.7%. Increasing the cut-point to ≥3, the PHQ-2-MZ has a sensitivity of 32.6% and a specificity of 94.6%.
Conclusions: The PHQ-9-MZ and PHQ-2-MZ emerge as two valid alternatives for screening for depression in primary health care settings in Mozambique. Depending on program needs and weighing the value of minimizing false positives and false negatives, the PHQ-9-MZ can be employed with cut-points ranging from ≥8 to ≥11, and the PHQ-2-MZ with cut-points ranging from ≥2 to ≥3.
The analysis of groundwater nitrate pollution and health risk assessment in Rural Areas of Yantai
Authors: Yu Guimei , Wang Song song , Wang Jiu , Liu Lei , Li Yun , Zhang Yi
Published: January 2020

Background: Nitrate is one of the most common chemical contaminants of groundwater, and it is an important unqualified factor of rural groundwater in Yantai. In order to assess the risk of exposure to drinking water nitrate for adults and juveniles, in recent years, we monitored the nitrate concentrations in rural drinking water, the HHRA model was also used to assess the human health risk of nitrate pollution in groundwater. Methods : From the year 2015 to 2018, the drinking water in rural areas of Yantai was tested according to the "Sanitary Standard for Drinking Water" (GB5749-2006). The principal component analysis was used to analyze the relationship between groundwater chemicals and nitrate. The HHRA model was used to assess human health risks of groundwater nitrate through the drinking water and skin contact. Results : A total of 2348 samples were tested during the year 2015-2018.Nitrate and total dissolved solids, total hardness, chloride are all relevant, the above indicators may come from the same source of pollution; The median nitrate content (C EXP50 ) was 17.8 mg / L; the C EXP95 was 53.4 mg / L; the risk of exposure in each group was ranked as: Juveniles > Adult female > Adult male;hazard quotient HQ 50 and HQ 95 for minors and adults exceed 1. Conclusions :The concentrations of nitrate is stable and does not change over time.The high concentration of nitrate in rural areas of Yantai may be the result of the interaction of fertilizers and geological factors. The risk of exposure to nitrate in juveniles and adults is above the limit, and HQ is over 1, so it is necessary to be on the alert for the high levels of nitrate.
Transcriptome analysis and molecular mechanism of linseed (Linum usitatissimum L.) drought tolerance under repeated drought using single-molecule long-read sequencing
Authors: Wang Wei , Wang Lei , Wang Ling , Tan Meilian , Ogutu Collins O. , Yin Ziyan , Zhou Jian , Wang Jiaomei , Wang Lijun , Yan Xingchu
Published: January 2020

Background Oil flax (Linum usitatissimum L.) also as known as linseed is one of the most important oil crops in the world. Although linseed was reported to show better tolerance to abiotic stress conditions compared to other oil crops, the molecular mechanisms underlying linseed tolerance to drought stress are largely unknown. Moreover, as a result of climate change, drought dramatically reduces linseed yield and quality, but so far very little is known about how linseed coordinates the drought-resistant genes expression of response to different level of drought stress on the genome-wide level. Results To explore the transcriptional response of linseed to drought stress (DS) and repeated drought stress (RD), we first determined the drought tolerance of different linseed varieties. Then we performed full-length transcriptome sequencing of drought-resistant variety (Z141) and drought-sensitive variety (NY-17) using single-molecule real-time sequencing and RNA-sequencing under drought stress (DS) and repeated drought stress (RD) at the seedling stage. Gene Ontology (GO) enrichment analysis showed that compared with NY-17, the up-regulated genes of Z141 were enriched in more functional pathways related to plant drought tolerance under drought stress. In addition, the number of up-regulated genes in linseed under RD was more 30% than it under DS. In addition, a total of, 4,436 linseed transcription factors were identified, of these, 1,190 genes were responsive to stress treatments. Finally, the expression patterns of proline biosynthesis and DNA repair structural genes were verified by RT- PCR. Conclusions Drought tolerance of Z141 may be related to its specifically up-regulated drought tolerance genes under drought stress. Several variable physiological responses occurred in repeated than in sustained drought treatment. Sum up, this study provides a new perspective to understand the drought adaptability of linseed.
Downregulation of Calreticulin and Annexin A2 in Cholesteatoma by 2-DE Analysis
Authors: Ho Kuen-Yao , Hung Kuo-Feng , Chien Chen-Yu , Chai Chee-Yin , Chen Wan-Tzu , Wang Hsun-Mo , Tsai Shih-Meng , Chan Leong-Perng , Chang Ning-Chia , Wu Yu-Jen
Published: January 2020

Background:
Many factors are thought to be associated with the development of cholesteatoma, while the mechanisms of its formation remain unclear. This study aimed to identify the potential mechanisms of the proliferation and growth of cholesteatoma by analysis of the differential expressions of proteins in cholesteatoma and retroauricular skin tissue collected from patients.
Methods:
Comparative proteomics analyses using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), in addition to immunohistochemical analysis, were conducted to identify differentially-expressed proteins in cholesteatoma tissue as compared with retroauricular skin tissue. Western blotting was also employed to verify the expression patterns of the specific proteins identified by 2-DE and to measure the changes in potential modulators related to cholesteatoma proliferation and growth.
Results:
Calreticulin (CRT) and annexin A2 (AnxA2) were identified as being differentially-expressed in cholesteatoma by 2-DE and LC-MS/MS, the results of which were in agreement with the results of immunohistochemical analysis and western blotting. Downregulation of CRT and AnxA2 were observed in cholesteatoma.
Conclusion:
Our data suggested that CRT and AnxA2 were associated with cholesteatoma. We speculated that the reduced expression of CRT and the persistent inflammatory response play important roles in the epithelial proliferation of cholesteatoma.
Loss of HtrA2/Omi protease activity induces mitonuclear imbalance and sarcopenia via differential regulation of mitochondrial biogenesis
Authors: Zhou Haohan , Yuan Danni , Gao Weinan , Tian Jiayi , Sun Hongyu , Yu Shuang , Sun Liankun , Wang Jincheng
Published: January 2020

Background Cellular homeostasis requires tight coordination between nucleus and mitochondria, organelles that each possess their own genomes. Disrupted mitonuclear communication has been found to be implicated in many aging processes. However little is known about mitonuclear signaling regulator in sarcopenia which is a major contributor to the risk of poor health-related quality of life, disability and premature death in older people. HtrA2/Omi is a mitochondrial protease and play an important role in mitochondrial proteostasis. HtrA2 mnd2(-/-) mice harboring protease-deficient HtrA2/Omi Ser276Cys missense mutants exhibit premature aging phenotype. Additionally, HtrA2/Omi has been established as a signaling regulator in nervous system and tumors. We therefore asked whether HtrA2/Omi participates in mitonuclear signaling regulation in aging muscle.Methods Using motor functional, histological and molecular biological methods, we characterized the muscle phenotype of HtrA2 mnd2(-/-) mice. We employed bioinformatics analysis and identified HtrA2/Omi as a gene differentially associated with nDNA/mtDNA gene expression in sarcopenia. Further, we isolated the gastrocnemius muscle of HtrA2 mnd2(-/-) mice and determined expression of genes in UPR mt , mitohormesis, electron transport chain (ETC), and mitochondrial biogenesis.Results Here, we showed that HtrA2/Omi protease deficiency induced denervation-independent skeletal muscle degeneration. Despite of mitochondrial hypofunction, upregulation of UPR mt and mitohormesis related genes and elevated reactive oxygen species (ROS) production were not observed in HtrA2 mnd2(-/-) mice, contrary to previous assumptions that loss of protease activity of HtrA2/Omi would lead to mitochondrial dysfunction as a result of proteostasis disturbance and ROS burst. Instead, we showed that HtrA2/Omi protease deficiency results in different changes between the expression of nDNA and mtDNA encoded ETC subunits, which is in consistent with their transcription factors NRF-1/2 and coactivator PGC-1α, suggesting that HtrA2/Omi protease activity may differentially regulate mitonuclear signaling via mitochondrial biogenesis in sarcopenia. Besides, Akt1 but not GSK3β showed increased expression level in HtrA2 mnd2(-/-) muscles, indicating an involvement of Akt1 in PGC-1α regulation response to HtrA2/Omi protease deficiency.Conclusions HtrA2/Omi protease deficiency induces mitonuclear imbalance and sarcopenia via differential regulation of mitochondrial biogenesis. The novel mechanistic insights may be of importance in developing new therapeutic strategies for sarcopenia.
Automatic group-wise whole-brain short association fiber bundle labeling based on clustering and cortical surface information
Authors: Vázquez Andrea , López-López Narciso , Houenou Josselin , Poupon Cyril , Mangin Jean-François , Ladra Susana , Guevara Pamela
Published: January 2020

Background: Diffusion MRI is the preferred non-invasive in vivo modality for the study of brain white matter connections. Tractography datasets contain 3D streamlines that can be analyzed to study the main brain white matter tracts. Fiber clustering methods have been used to automatically regroup similar fibers into clusters. However, due to inter-subject variability and artifacts, the resulting clusters are difficult to process for finding common connections across subjects, specially for superficial white matter. Methods: We present an automatic method for labeling of short association bundles on a group of subjects. The method is based on an intra-subject fiber clustering that generates compact fiber clusters. Posteriorly, the clusters are labeled based on the cortical connectivity of the fibers, taking as reference the Desikan-Killiany atlas, and named according to their relative position along one axis. Finally, two different strategies were applied and compared for the labeling of inter-subject bundles: a matching with the Hungarian algorithm, and a well-known fiber clustering algorithm, called QuickBundles. Results: Individual labeling was executed over four subjects, with an execution time of 3.6 minutes. An inspection of individual labeling based on a distance measure, showed good correspondence among the four tested subjects. Two inter-subject labeling were successfully implemented and applied to 20 subjects, and compared using a set of distance thresholds, ranging from a conservative value of 10 mm to a moderate value of 21 mm. Hungarian algorithm led to high correspondence, but low reproducibility for all the thresholds, with 96 seconds of execution time. QuickBundles led to better correspondence, reproducibility and short execution time of 9 seconds. Hence, the whole processing for the inter-subject labeling over 20 subjects takes 1.17 hours. Conclusion: We implemented a method for the automatic labeling of short bundles in individuals, based on an intra-subject clustering and the connectivity of the clusters with the cortex. The labels provide useful information for the visualization and analysis of individual connections, what is very difficult without any additional information. Furthermore, we provide two fast inter-subject bundle labeling methods. The obtained clusters could be used for performing manual or automatic connectivity analysis in individuals or across subjects. Keywords: fiber labeling; clustering; fiber bundle; tractography; superficial white matter
Genes gained and lost during the evolution and domestication of Brassica napus
Authors: Zhou Hong , Ye Xueling , Ma Yanling , Hu Haiyan , Wei Yuming , Youliang Zheng , Liu Yaxi , Liu Chunji
Published: January 2020

Background: Brassica napus is one of the most important sources of vegetable oil for human nutrition and biofuel. It is an allotetraploid formed about 7500 years ago by hybridization between B. rapa and B. oleracea. Results from earlier studies show that the allopolyploidization process was accompanied by rapid and intensive changes and abundant homoeologous exchanges between the subgenomes have been accumulated during its short history of evolution. Results: By comparing differences between 19 artificially synthesized and 30 natural genotypes, we assessed possible changes in gene ratio, diversity and functional groups during the evolution and domestication of this species. This comparison revealed that gene ratio and diversity between the two subgenomes have hardly changed. However, large numbers of genes have been lost and many new genes gained. Compared with the artificial genotypes, the natural ones contain much lower proportions of genes conferring resistance and tolerance to biotic and abiotic stresses but much higher proportions of genes associated with seeds development and metabolic processes. The diploid donor for the A subgenome of B. napus contributed more genes involved in agronomic traits and the C subgenome donor contributed more genes related to cellular development and metabolic process. Conclusions: Our results show that genes conditioning resistance and tolerance to both biotic and abiotic stresses have suffered stronger selection during the evolution and domestication of B. napus, and that changes in different aspects including gene content and genome size in the allotetraploid are not random but dictated by its two diploid donors.
Genome-centric metagenomic insights into the impact of alkaline/acid and thermal sludge pre-treatment on digestion sludge microbiome
Authors: Wang Shanquan , Liang Zhiwei , Shi Jiangjian , Wang Chen , Li Junhui , He Zhili
Published: January 2020

Background: Wastewater treatment generates large amounts of waste activated sludge (WAS), which mainly consist of recalcitrant microbial cells and particulate organic matter. WAS pre-treatment is an effective way to destabilize sludge floc structure and release cellular macromolecules and other organic matter for improvement of digestion efficiency. Nonetheless, impacts of WAS pre-treatment on the complex digestion sludge microbiome, as well as mechanistic insight into how sludge pre-treatment improve digestion performance, remain to be elucidated. Results: In this study, genome-centric metagenomic approach was employed to investigate the digestion sludge microbiome in four methanogenic sludge digesters with different feeding sludge: APAD, WAS pre-treated with 0.25 mol/L alkaline/acid; HS-APAD, WAS pre-treated with 0.8 mol/L alkaline/acid; Thermal-AD, thermal pre-treated WAS; Control-AD, fresh WAS. We retrieved 254 metagenomic-assembled genomes (MAGs) to identify the key functional populations involved in methanogenic digestion process. These MAGs span 28 phyla with 69 of them as yet-to-be-cultivated lineages, and 30 novel lineages were characterized with metabolic potential associated with hydrolysis and fermentation. Interestingly, functional populations involving carbohydrate digestion were overrepresented in APAD and HS-APAD, while lineages related to protein and lipid fermentation were overrepresented in Thermal-AD, reflecting different digestion substrates released from alkaline/acid and thermal pre-treatments. Of the three major functional populations, i.e., fermentative bacteria, acetogenic syntrophs and methanogens, significant correlations between genome sizes of the fermentative bacteria and their abundance were observed, particularly in the APAD and HS-APAD with improved digestion performance. Conclusion: These genome-centric metagenomic insights advance our understanding of sludge pre-treatment on digestion sludge microbiomes, shedding light on future optimization of methanogenic sludge digestion and resource recovery.
Hygiene Hypothesis: Association between Hygiene and Asthma among Preschool Children in Lebanon
Authors: Hallit Souheil , Sacre Hala , Kheir Nelly , Hobeika Eva , Hallit Rabih , Waked Mirna , Salameh Pascale
Published: January 2020

Background Our objective was the validation of a scale to assess the hygiene hypothesis and the link between hygiene, and asthma among 3 to 5 years old Lebanese children in preschool.Methods Between November 2018 and March 2019, this cross-sectional study was carried out, enrolled 515 preschool children’ asthma and potential risk factors, including hygiene, were assessed using a standardized questionnaire. A specific hygiene hypothesis related scale was generated and validated for this purpose.Results Items related to the hygiene hypothesis scale have led to a convergence over a nine factors solution, having over than 1 Eigenvalue, which explains the variance total of 65.86%. Cronbach’s alpha values corresponding to the hygiene hypothesis related scale (0.696) was deemed acceptable. The backward logistic regression, taking as dependent variable the asthma’s presence or absence in child, showed that living in prairie (ORa=2.42), playing outside (ORa=2.80), having respiratory problems (ORa=4.18), attending a kindergarten (ORa=2.76), and having a sister with seasonal allergy (ORa=6.86) had significant association with increased odds of occurrence of children’s asthma. The hygiene hypothesis related score was not found to be associated with increased asthma odds (p=0.663).Conclusion Current findings suggested that home cleaning and personal cleanliness were not correlated with asthma in preschool children. Future studies will require more in-depth analyses of microbial exposure, allowing proper identification of unequivocal species and functional characteristics.
In vitro evaluation of novel Zeolite-hydroxyapatite blended scaffold for dental tissue engineering
Authors: Mohandesnezhad Sanam , Alizadeh Effat , Pilehvar-Soltanahmadi Yunes , Davaran Soodabeh , Goodarzi Arash , Khatamian Masoumeh , Zarghami Nosratollah , Samiei Mohammad , Aghazadeh Marzieh , akbarzadeh abolfazl
Published: January 2020

Main purpose of tissue engineering is creating appropriate conditions for the regeneration of tissues. Dental pulp-derived stem cells due to differentiation capacity and angiogenic properties have potential to regenerate dental pulp tissue. In the current experimental study poly caprolactone and poly L-lactic acid were synthesized by ring-opening polymerization method. The nano-hydroxyapatite and Zeolite were obtained by hydrothermal method. Morphological features and crystals properties of nHA and Zeolite were studied by X-ray diffraction. Nanofibers were fabricated using electrospinning method and investigated by FT-IR spectroscopy. DPSCs obtained from human source and proliferation and viability of them on electrospun scaffolds were evaluated by MTT assay. Also, the adhesion and proliferation of hDPSCs were investigated by SEM. The results showed that hDPSCs have the most viability and proliferation on the 1 st , 7 th , 14 th days on PCL-PLA/Zeolite scaffolds and maximum on the 3 rd day on PCL-PLA/nHA scaffolds. On the days of 7 th and 14 th , cell growth on scaffolds containing both nHA and Zeolite is better than sample that nHA is used alone with PCL-PLA. Briefly, by these results can be understand that Zeolite is a good agent in bone and tooth tissue engineering applications. More studies requires to investigate Zeolite effect on scaffold properties.
Shifting Demographics and Comorbidity Burden in Chinese Urban Patients With Chronic Hepatitis B, 2013 and 2016
Authors: Hou Jinlin , Chen Wendong , Ying Han , Wang Lei , Lee I-Heng Emma , Hsu Ling-I , Xie Dongying , Yin Xueru , Hou Fengqin , Yang Yida
Published: January 2020

Background: The long-term safety of anti-hepatitis B virus (HBV) therapies is critical to assess, particularly in the context of aging chronic hepatitis B (CHB) populations and accumulating comorbidities. HBV is common and clinically consequential in China; however, the demographics and comorbidity burden of this population have not been fully characterized.Aim: To characterize changes in demographics and comorbidity burden of urban Chinese patients with CHB between 2013 and 2016. Methods: The China Health Insurance Research Association (CHIRA) annual urban health insurance claims database from 2013 and 2016 was used to identify adults with ≥1 ICD-10 code for CHB. Descriptive analyses were conducted to compare age and comorbidities distributions between 2013 and 2016.Results: Median age increased from 40 in 2013 (N=14,545) to 44 in 2016 (N=11,648) (P<0.001). The proportion of patients aged >45 years increased significantly from 40.3% in 2013 to 49% in 2016 (P<0.001). Significant increases in multiple comorbidities were observed, including hypertension (9.4% to 14.5%), hyperlipidemia (4.7% to 7.0%), and cardiovascular disease (5.7% to 10%) (P<0.001 for all comparisons). Increases were also observed in renal impairment (8.8% to 10.0%; P<0.001) and osteoporosis and/or pathologic nontraumatic bone fracture (3.8% to 7.3%; P<0.001). Conclusions: Even over the short interval assessed in this study, there was a significant shift in the characteristics of urban CHB patients in China. Aging of the population was accompanied by significant increases in the percentage of patients having potentially concerning comorbidities. Careful selection of treatment options and comorbidity monitoring should be considered when managing Chinese patients with CHB.
Physiological Effects of the Combined Stresses of Freeze-thaw, Acid Precipitation and Deicing Salt on Alfalfa Seedlings
Authors: Bao Guozhang , Tang Wenyi , An Qirui , Liu Yaoxin , Tian Jiaqi , Zhao Nan , Zhu Saning
Published: January 2020

BackgroundIn the early spring of northern China, the combined stresses of freeze-thaw, deicing salt and acid deposition are the main ecological threats to the urban turf ecosystem. ResultsWe studied changes in the Malondialdehyde (MDA), protein, soluble sugar, proline and chlorophyll contents of DongMu No. 1seedlings of 8 treatment combination groups which are imposed by freeze-thaw (F), acid rain (A) and deicing salt (D). An increasing in MDA content showed that the membrane system of seedlings was damaged under combined stress (F+A+D). The changes indicated that under the adverse conditions, the proline and soluble sugar contents increased obviously with the accumulation of MDA in the plants, while the chlorophyll content decreased significantly.ConclusionPlants can alleviate the damage caused by stress by increasing soluble sugars and by regulating the proline content to maintain osmotic balance.
Identification and analysis of CYP450 supergene family members from the transcriptome of Aralia elata (Miq.) Seem reveal candidate genes for triterpenoid saponins biosynthesis
Authors: Cheng Yao , Liu Hanbing , Tong Xuejiao , Zhang Xin , Li Dalong , Jiang Xinmei , Yu Xihong
Published: January 2020

BackgroundMembers of the cytochrome P450 (CYP450) gene superfamily have been shown to play essential roles in regulating secondary metabolites biosynthesis. However, the systematic identification and bioinformatics analysis of CYP450s have not been reported in Aralia elata (Miq.) Seem, a highly valued medicinal plant. ResultsIn the present study we conducted the RNA-sequencing (RNA-seq) analysis of the leaves, stems, and roots of A. elata, yielding 66,713 total unigenes. Following the annotation and classification of these unigenes, we were able to identify two pathways and 19 putative genes associated with the synthesis of triterpenoid saponins in these plants, with qRT-PCR subsequently being used to validate these gene expression patterns. Scanning with the CYP450 model from Pfam resulted in the identification of 111 full-length and 143 partial-length CYP450s, with the full-length CYP450s being further clustered into 7 clans and 36 families. Through phylogenetic and conserved motif analyses, we were further able to group these CYP450 proteins into two primary branches: A-type (53%) and non-A type (47%). We further conducted representative protein sequence alignment for these CYP450 family members, with secondary elements being assigned in light of the recently published Arabidopsis CYP90B1 structure. Using the available sequence information, we further identified predicted substrate recognition sites (SRSs) and substrate binding sites within these putative proteins.We further assessed the expression patterns of these 111 CYP450 genes across A. elata tissues, with 12 members of this gene family being selected at random for qRT-PCR validation. From these data, we identified CYP716A295 and CYP716A296 as the candidate genes most likely to be associated with oleanolic acid synthesis, while CYP72A763 was identified as being the most likely to play a role in hederagenin biosynthesis. Finally, we assessed the subcellular localization of these CYP450 proteins within Arabidopsis protoplasts, highlighting the fact that they localize to the endoplasmic reticulum.ConclusionsThis study presents a systematic analysis of the CYP450 gene family in A. elata and provided a foundation for further functional characterization of CYP450 genes.