bluuebunny/crossref_metadata_2025 huggingface dataset:
NETs By-products and Extracellular DNA May Play a Key Role in COVID-19 Pathogenesis: Incidence on Patient Monitoring and Therapy
Authors: Thierry Alain , ROCH Benoit
Published: April 2020

Neutrophils play an important role as the first line of innate immune defense. One function of neutrophils, called neutrophil extracellular traps (NETs), has been discovered recently. NETs are extensive fibrous structures released extracellularly from activated neutrophils in response to infection. They are composed of cytosolic protein assembled on a scaffold of released chromatin. These structures suppress the dissemination of micro-organisms in blood by trapping them mechanically, and by exploiting coagulant function to segregate them within the circulation. In addition, NET components (DNA, histone, and granule proteins) also contribute to the triggering of an inflammatory process. NET function, however, can be regarded as a double-edged sword. On one hand, NET formation is an efficient strategy for neutralizing invading micro-organisms. On the other hand, NET can be harmful to the host, as its exposed by-products that are toxic to endothelial cells and parenchymal tissue. We present here the analogous biological and physiological features of the harmful positive amplification loop between inflammation and tissue damage induced by NETosis dysregulation and Coronavirus Disease-2019 (COVID-19) pathogenesis. Considering the rapid evolution of this disease symptoms and its lethality, we hypothesize that COVID-19 progresses under an amplifier loop, leading to an massive, uncontrolled inflammation process. We also describe the correlations of COVID-19 symptoms and biological features with those consecutive to uncontrolled NET formation causing various sterile or infectious diseases. General clinical conditions, and numerous pathological and biological features, are analogous with NETs deleterious effects. We postulate that Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) induces a disproportionate virus-induced NET release, and that this plays a key role in COVID-19 pathogenesis. While neutrophils are the principal starting point for extracellular and circulating DNA release, targeting NETs rather than neutrophils themselves may stand for an effective strategy. This paper offers an in-depth review of NET formation, function and pathogenic dysregulation, as well as of current and future therapies to control NET unbalance. As such, it enables us also to suggest new therapeutic strategies to fight COVID-19. In combination with or independent of the latest tested approaches, we propose that, in the short term, deoxyribonuclease I (DNase-1) treatment should be evaluated; we also advocate a significant increase in research on the development of toll-like receptors (TLR) and C-type Lectin like receptors (CLEC) inhibitors, and on anti-IL26 therapies.
Partial Unlock Caseload Management for COVID-19 Can Save 1-2 Million Lives Worldwide
Authors: Shuler Robert , Koukouvitis Theodore
Published: April 2020

This paper analyzes the stability and usefulness of a human-in-the-loop caseload management method for COVID-19. This can control the balance between medical resource utilization and economic shutdown duration across significant scenario variation. It reduce the total cases by controlling the rate of spreading as groups cross the herd immunity threshold, and suggests late intervention has more effect on total cases than early intervention once containment has failed. Data as of April 11, 2020 show that “flattening” strategy for COVID-19 in both the world and the U.S. is working so well that a significantly effective removal of social distancing (aka “unlock”) at any time in the next few years, other than after widespread and effective vaccination, will produce a rebound overloading the healthcare system. For the world, by early April flattening was working so well that a world rebound could be projected in 2021 that would exceed in critical demand even the additional million or so ventilators requested by world governments. In the U.S., whose trajectory is somewhat ahead of the world, the projected rebound of a late year unlock is already greater than the current crisis projected peak. Most citizens are tacitly expecting much sooner rather than much later unlocks. Leaving economies locked down for a long time is its own catastrophe, especially for countries that cannot provide substantial economic aid to their citizens. An SIR-type model was used with clear parameters suitable for public information, and both tracking and predictive capabilities, and an additional simulation of a decision-maker on selected-day partial unlock designed mainly to manage ventilator or other critical resource utilization, to make sure they are neither idle nor over committed. Using certain days of the week, already practiced by some countries, is not a necessary part of the method, but was used in the simulation to give a highly quantified unlock scheme. It also helps restore economic activity. While the model shows total cumulative cases, and therefore deaths, declining initially with flattening, when flattening begins to produce large rebounds the death rate goes back up. Partial unlock to manage critical resources brings the cumulative cases down about 8-12% between now and the second half of 2021, and therefore saves lives with some degree of certainty.
Extracellular Vesicles: The New Frontier of Stem Cell Regenerative Medicine?
Authors: Barreca Maria Magdalena , Cancemi Patrizia , Geraci Fabiana
Published: April 2020

Regenerative medicine aims to repair damaged or missing cells, tissues or organs for the treatment of various diseases, poorly managed with conventional drugs and medical procedures. To date there are different approaches to obtain these results. Multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells and derived products are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote tissue and organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects in damaged tissue restore are not depending on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release Extracellular Vesicles (EVs). EVs play a fundamental role in cell-to cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms trough which EVs carry out their therapeutic action and their possible application for the treatment of several diseases.
Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress
Authors: Carr Anitra C. , Spencer Emma , Dixon Liane , Chambers Steve
Published: April 2020

Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the intensive care unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and haematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, a marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs 56 ± 24 µmol/L, P <0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs 24 ± 14 µmol/L, P = 0.02). The total pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (P < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples form 28% of the cohort (mean 2.7 ± 1.7 days; range 1-7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (P = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Due to the important roles that vitamin C plays in the immune system, low vitamin C status is possibly both a cause and a consequence of the disease. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease oxidative stress and aid in their recovery.
Self-Regulated Learning Microanalysis For The Study Of The Performance Of Clinical Examinations By Physiotherapy Students
Authors: Medina Raquel , Álamo-Arce Daniel David , de Castro Felipe Rodríguez , Fernandez Dario Cecilio , Sandars John , Costa Manuel João
Published: April 2020

Background Students require feedback on their self-regulated learning (SRL) processes to improve the performance of clinical examinations. The key SRL processes used by students can be identified by SRL-micro-analysis but, this method has not been previously applied to physiotherapy students. The aim of this pilot study was to test a research design that might allow the evaluation of the potential usefulness of SRL microanalysis for the identification of key SRL processes used by physiotherapy students during the performance of a clinical examination skill.. The objectives of the pilot study were: 1) to evaluate whether SRL-microanalysis could identify differences in the use of SRL processes between successful and unsuccessful students; 2) to evaluate the reliability of SRL microanalysis ratings produced by different assessors.Methods SRL-microanalysis was used with second year physiotherapy students of a Spanish university (n= 26) as they performed a goniometric task. The task required students to obtain a goniometric measurement of the shoulder joint of a peer. Two assessors evaluated student performance and conducted the SRL- microanalysis with all students. An analysis of inter-rater reliability was performed to evaluate the degree of agreement between assessors. Results The SRL-microanalysis revealed differences in the use of key SRL processes between successful (n= 15: 57.0%) and unsuccessful performers (n= 11: 43.0%): The differences were particularly evident in strategic planning and self-monitoring skills. There was good inter-rater reliability for scoring of strategic planning (k=0.792), self-monitoring (k=0.946) and self-evaluation (k=0.846).Conclusion The use of SRL microanalysis characterized the key SRL processes of physiotherapy students performing a clinical skill with reliability between the assessors. This pilot study supports the potential usefulness of SRL-microanalysis for the identification of key SRL processes in physiotherapy education. Therefore, this study paves the way to the development of a full study, with a larger number of students and more diverse clinical tasks, to evaluate the SRL processes in successful and unsuccessful students.
Smokeless tobacco use: its prevalence and relationships with dental symptoms, nutritional status and blood pressure among rural women in Burkina Faso
Authors: Diendéré Jeoffray , Zeba Augustin Nawidimbasba , Nikiéma Leon , Kaboré Ahmed , Savadogo Paul Windinpsidi , Tougouma Somnoma Jean Baptiste , Tinto Halidou , Ouédraogo Arouna
Published: April 2020

Background: Sub-Saharan women use smokeless tobacco (SLT) more than smoked tobacco. Among Western African countries, the estimated weighted prevalence of SLT use in rural women was found to be the highest in Burkina Faso (after Sierra Leone). This study aimed to assess the prevalence of SLT use and its associated factors among rural women in Burkina Faso by using nationally representative data.Methods: We used data from the 2013 STEPwise approach to Surveillance (STEPS) study, which provided sociodemographic, clinical (anthropometric, systolic blood pressure [SBP], diastolic blood pressure [DBP] and dental symptoms), biological (total and high-density lipoprotein cholesterol and fasting blood sugar), and tobacco and alcohol consumption data. Data for 1730 rural women were used, and we performed Student’s chi-squared and logistic regression analyses.Results: The prevalence of current SLT use was 13.8% (95% CI: 12.2-15.5). Significant risks for SLT use were the presence of dental symptoms (adjusted odds ratio [aOR] = 2.59; p<0.001), undernourishment (aOR = 1.78; p<0.01), decreased waist circumference (aOR = 0.98; p<0.05), decreased DBP (aOR = 0.97; p<0.01), increased SBP (aOR = 1.01; p<0.05), and increased differential blood pressure (aOR = 1.01; p<0.05). The co-use of alcohol was also a significant risk factor (aOR = 2.80; p<0.001).Conclusion: The prevalence of current SLT use was high among rural women in Burkina Faso, and significant concerns for users included alcohol co-use, the occurrence of dental symptoms, undernourishment, and an increase in differential blood pressure. National Public Health interventions are needed to reduce SLT use and its health-related concerns.
The influence of balanced complex chromosomal rearrangements on preimplantation embryonic development potential and molecular karyotype
Authors: Li Gang , Shi Weiyi , Niu Wenbin , Xu Jiawei , Guo Yihong , Su Yingchun , Sun Yingpu
Published: April 2020

Background: Balanced complex chromosome rearrangements (BCCR) are balanced chromosomal structural aberrations that involve two or more chromosomes and at least three breakpoints. It is very rare in the population.The objective is to explore the difference of influence of three types of BCCR on early embryonic development and molecular karyotype.Results:Twelve couples were recruited including four couples of three-way rearrangements carriers (group A), three couples of double two-way translocations carriers (group B) and five couples of exceptional CCR carriers (group C). A total of 243 oocytes were retrievedin the seventeen preimplantation genetic testing (PGT) cycles, and 207 of these were available for fertilization.After intracytoplasmic sperm injection, 181oocytes normally fertilized. The rates of embryos forming on day3 in three groups were 87.88%, 97.78% and77.14%, which was significantly different (P=0.01). Compared with group B, the rate of embryo formation was statistically significantly lower in group C(P=0.01).Furthermore, the rates of high-quality blastocysts in three group were 14.71%, 48.15% and 62.96%, respectively, which was significantly different (P=0.00). Compared with group B andC, the rate of high-quality blastocysts in group A was statistically significantly lower (P=0.00;P=0.00). Comprehensive chromosome analysis was performed on 83 embryos, including 75 trophectodermcellsand 8 blastomeres. Except 7 embryos failed to amplify, 9.01%embryos were diagnosed as euploidy, and 90.91% were diagnosed as abnormal. As for group A, the euploid embryo rate was 10.71%and the abnormal embryo rate was 89.29%. In group B,the euploid embryo rate was 3.85%, the abnormal embryo rate was 96.15%. The euploid embryo rate was 13.04%, the abnormal embryo rate was 86.96% in group C.There were no significant differences among the three groups (P = 0.55).Conclusions:The lowest rate of high quality blastocysts has been for three-way rearrangements and the lowest rate of euploidy has been for double two-way translocations, although no significant difference. Different types of BCCR maybe have little effect on the embryonic molecular karyotype. The difference of influence of BCCR on early embryonic developmentandmolecular karyotypeshould be further studied.
Lonely places or lonely people? Investigating the relationship between loneliness and place of residence
Authors: Victor Christina R , Pikhartova Jitka
Published: April 2020

Background: Loneliness in later life is largely presented as a problem of the individual focusing upon antecedents such as demographic or health factors. Research examining the role of the broader living environments is much rarer. We examined the relationship between loneliness and three dimensions of the lived environment: geographical region, deprivation, and area classification (urban or rural).Methods: Our sample consisted of 4,663 core members (44% males) aged 50+ (wave 7 mean age 72.8, S.D.= 7.1) present both in waves 3 (2006) and 7 (2014) of the English Longitudinal Study of Ageing (ELSA). Loneliness was measured using two approaches, individual and area-based, and both waves included these questions. Individual-based (self-reported) loneliness was assessed using the three item University of California Los Angeles (UCLA) scale (ranging from 3 =not lonely to 9= lonely with a score of 6+ defining loneliness. We also used a novel question which asked participants to evaluate how often they felt lonely in their area of residence (area-based; ranging from 1=often to 7=never, using cut off 4+ to define loneliness). The lived environment was classified in three different ways: the Index of Multiple Deprivation (IMD), Government Office Regions (GOR), and area classification (urban or rural). Covariates with established relationship with loneliness including demographic factors, social engagement and health, were included in the analyses. Results: In wave 7, the prevalence of individual-based loneliness was 18% and area-based was 25%. There was limited congruence between measures: 68% participants reported no individual- or area-based loneliness and 9% reported loneliness for both measures. After adjusting for individual co-variates only one significant relationship was observed between loneliness and area -based characteristics. A significant association was observed between area-based loneliness and deprivation score, with higher levels of loneliness in more deprived areas (OR=1.4 for highest quintile of deprivation). Conclusions: Our results indicate that loneliness in older adults is higher in the most deprived areas independent of individual-level factors. In order to develop appropriate interventions further research is required to investigate how area-level factors combine with individual-level loneliness vulnerability measures to generate increased levels of loneliness in deprived areas.
Different profiles of body mass index variation among patients with multidrug-resistant tuberculosis: a retrospective cohort study.
Authors: Diallo Alhassane , Diallo Boubacar Djelo , Camara Lansana Mady , Kounoudji Lucrèce Ahouéfa Nadège , Bah Boubacar , N’Zabintawali Fulgence , Carlos-Bolumbu Miguel , Diallo Mamadou Hassimiou , Sow Oumou Younoussa
Published: April 2020

Background: Despite the predictive role of body weight variation in treatment outcome in multidrug-resistant tuberculosis (MDR-TB), few corroborating data are available. We studied weight variation in patients with MDR-TB to identify groups of weight change and to determine factors that influence these changes. Methods: We analyzed patients with rifampicin resistance who were treated with an MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 at three major drug-resistant TB centers in Guinea. Patients were seen monthly until the end of treatment. Clinical outcome was the body mass index (BMI). We used a linear mixed model to analyze trajectories of BMI and a latent class mixed model to identify groups of BMI trajectories. Results: Of 232 patients treated for MDR-TB during the study period, 165 were analyzed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3 – 8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m 2 . Factors associated with faster BMI progression were success of MDR-TB treatment (0.24 [SE 0.09] per kg/m 2 ; p = 0.0205) and absence of lung cavities on X-ray (0.18 [0.06] per kg/m 2 ; p = 0.0068). Two groups of BMI change were identified: rapid BMI increase (n = 121; 85%) and slow BMI increase (n = 22; 15%). Patients in the slow BMI increase group were mostly female (68%) had no history of TB treatment (41%), had a positive HIV infection (59%), and had a more severe clinical condition at baseline, characterized by a higher frequency of symptoms including depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelet count, and higher SGOT. These patients also had a longer time to initial culture conversion (log-rank test: p = 0.0087). Conclusion: Quantitative BMI data on patients with MDR-TB treated with a short regimen allowed the identification of subgroups of patients with different trajectories of BMI and emphasized the usefulness of BMI as a biomarker for the monitoring of MDR-TB treatment outcome.
Caregiver Burden is Reduced by Personalized Social Support for Non-Dependent Old Persons: a Longitudinal Study of 876 Old Persons and Their Caregivers
Authors: Arlotto Sylvie , Gentile Stéphanie , Durand Anne Claire , Bonin-Guillaume Sylvie
Published: April 2020

Background. Informal care provided by family caregivers to old persons is associated with a high risk of burden and poor health status. This study aimed to analyze the impact of Personalized Social Support (PSS) for non-dependent old persons living in the community on caregiver burden, satisfaction, and frailty. Methods. This non-interventional longitudinal study was performed in the southeast of France: old persons asking for PSS (>70 years of age, with no disability and no severe chronic disease, living at home) and their caregivers were included with a 6-month follow-up. Eligible dyads were visited at home by social workers. Caregiver burden was assessed with Mini-Zarit and frailty status with FiND (Frail Non-Disabled).Results. 876 dyads were eligible for PSS. Old persons were 82.2 ± 5.8 years old and 77.6% were women. Most caregivers were women (64.5%). Most caregivers were the children of the old person (61%), the rest were mostly spouses. Nearly 64% of old persons were frail and 38% were highly dependent. Follow-up was conducted for 686 dyads (78.3%). Of these, only 569 had PSS. The PSS was mainly for housework and meal preparation. At the time of follow-up, 53% of the caregivers for whom the old person had PSS had less difficulty helping their old person. Two-thirds (61.5%) of caregivers were fully satisfied with the PSS. Whether or not they had received the PSS, 73% of caregivers had reduced burden at 6 months, only 6% still had a high burden, 17% were less frail, and 18% felt healthier than at the time of inclusion.Conclusions. Our study highlights that non-dependent old person’s caregivers also experience burden. Implementing social support for activities of daily living had a major impact on their burden but not on their level of frailty. This means that the determinants of caregiver frailty are more complex and further studies are needed.
Relationship between Internet addiction and sleep disturbance in high school students: a cross-sectional study
Authors: Tokiya Mikiko , Itani Osamu , Otsuka Yuichiro , Kaneita Yoshitaka
Published: April 2020

Background: Worldwide, the increase in the number of Internet users has increased Internet dependence. In adolescents, this dependence interferes with sleep, which is important for the development of psychophysiological capabilities. However, few large-scale surveys have descriptively examined the relationship between Internet addiction (IA) and sleep disturbance using standardized questionnaires. We conducted this study to determine the relationship between sleep disturbance in adolescents and IA based on the categories of the Young Diagnostic Questionnaire (YDQ) through a complete survey of one prefecture in Japan. Methods: In 2016, a self-report questionnaire was used to survey high school students (n=10,405, age range: 15–16 years) in all 54 day-boarding high schools in the selected prefecture. We defined “sleep disturbance” by scores greater than 5.5 points on the Japanese version of the Pittsburgh Sleep Quality Index. IA was evaluated using the YDQ: “IA,” when 5 of the 8 YDQ items were present; “at-risk,” when either 3 or 4 YDQ items were reported; and “non-IA,” when less than 2 YDQ items were positive. Multiple logistic regression analysis was undertaken with sleep disturbance as the dependent variable, IA as the explanatory variable, and adjustments for 8 items. Results: High YDQ scores were associated with high prevalence rates of sleep disturbance in both male and female participants. These findings persisted after controlling for other factors in the multiple regression model. Conclusions: Among Japanese adolescents, there exists a significant independent relationship between IA and sleep disturbances.
Prevalence, antimicrobial susceptibility patterns, serotypes and risk factors for group B streptococcus rectovaginal isolates among pregnant women at Kenyatta National Hospital, Kenya; A cross-sectional study
Authors: Salano Jisuvei Clayton , Alfred Osoti , Njeri Maina Anne
Published: April 2020

Background Estimates of group B streptococcus ( GBS) disease burden, antimicrobial susceptibility, and serotypes in pregnant women are limited for many resource-limited countries including Kenya. These data are required to inform recommendations for prophylaxis and treatment of infections due to GBS. Methods We evaluated the prevalence, antimicrobial susceptibility patterns, serotypes, and risk factors associated with rectovaginal GBS colonization among pregnant women receiving antenatal care at Kenyatta National Hospital (KNH) between August and November 2017. Consenting pregnant women between 12 and 40 weeks of gestation were enrolled. Interview-administered questionnaires were used to assess risk factors associated with GBS colonization. An anorectal swab and a lower vaginal swab were collected and cultured on Granada agar for GBS isolation. Positive colonies were tested for antimicrobial susceptibility to penicillin G, ampicillin, vancomycin, and clindamycin using the disk diffusion method. Serotyping was performed by latex agglutination. Logistic regression was used to identify factors associated with GBS colonization. Results A total of 292 women were enrolled. Median age was 30 years (Interquatile range {IQR} 26-35) with a median gestational age of 35 weeks (IQR 30-37). Overall GBS was identified in 60/292 (20.5%) of participants. Among the positive isolates, resistance was detected for penicillin G in 42/58 (72.4%) isolates, ampicillin in 32/58 (55.2%) isolates, clindamycin in 14/46 (30.4%) isolates, and vancomycin in 14/58 (24.1%) isolates. All ten GBS serotypes were isolated, and 37/53 (69.8%) of GBS positive participants were colonized by more than one serotype. None of the risk factors was associated with GBS colonization. Conclusion The prevalence of GBS colonization was high among mothers attending antenatal clinic at KNH. In addition, a high proportion of GBS isolates were resistant to commonly prescribed intrapartum antibiotics. Hence, other measures like GBS vaccination is a potentially useful approaches to GBS prevention and control in this population. Screening of pregnant mothers for GBS colonization should be introduced and antimicrobial susceptibility test performed on GBS positive samples to guide antibiotic prophylaxis.
Synthesis and biological evaluation of 4-substituted aryl-piperazine derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-azatricyclo [5.2.1.02,6] dec-8-ene-3,5-dione as anti-cancer and anti-angiogenesis agents
Authors: Guo Lifang , Xu Benshan , Wan Zirui , Ren Lulu , Zhang Jie , Zhang Wen , Liu He , Liu Lihong
Published: April 2020

The authors have requested that this preprint be removed from Research Square.
M1 macrophage activation in severe Plasmodium falciparum malaria patients with pulmonary oedema
Authors: Klinkhamhom Aekkarin , Glaharn Supattra , Sris Charit , Ampawong Sumate , Krudsood Srivicha , Ward Stephen A. , Viriyavejakul Parnpen
Published: April 2020

Background Pulmonary oedema (PE) is a serious complication of severe P. falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarisation is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarisation of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients with and without evidence of PE. Methods Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorised into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68- all macrophages, CD40- M1 macrophage and CD163- M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes.Results Lung injury was demonstrated in malaria patients with PE. The expression of CD40 (M1 macrophage) was prominent in the group of severe P. falciparum malaria patients with PE (p < 0.05), whereas there was no difference observed for CD163 (M2 macrophage) between PE and non-PE groups. Conclusions The study demonstrates M1 polarisation in lung tissues from severe P. falciparum malaria infections with PE. Understanding the nature of macrophage characterisation in malaria infection may provide new insights into therapeutic approaches that could be deployed to reduce lung damage in severe P. falciparum malaria.
Maintenance considerations in elderly dependent patients with implants
Authors: Sato Yuji , Koyama Shigeto , Ohkubo Chikahiro , Ogura Shin , Kamijo Ryutaro , Sato Soh , Aida Jun , Izumi Yuichi , Atsum Mihoko , Isobe Akio , Baba Shunsuke , Ikum Noriharu , Watanabe Fumihiko
Published: April 2020

Background Self-care and professional care of implants may prove difficult for elderly people who require nursing care. However, the actual state of care and problems remains unknown. In this study, we investigated the actual state of implant problems in elderly people living in their own home or in a nursing home who received visiting dental treatment. Methods We mailed questionnaire survey forms to 2339 representatives or specialists who were members of the Japanese Society of Oral Implantology, the Japanese Society of Gerodontology or the Japan Prosthodontic Society. We narrowed down the respondents to those who provided visiting dental treatment, and analyzed the actual state of implants observed during visiting dental treatment (type, care, problems, countermeasures, etc.). Results Of the 924 dentists who responded to the questionnaire survey, 291 (22%) provided visiting dental treatment . While the majority of implant types encountered in the previous 12 months were root-form implants, there were still a certain number of blade and subperiosteal implants. Daily implant care involved mostly cleaning with a toothbrush + auxiliary tools. The most frequent implant problems encountered in the past were difficulty in cleaning and peri-implantitis. Medication and antiphlogistic treatment were most frequently adopted as countermeasures to implant problems, followed by observation. When we classified the results into those for the dentists who provided implant treatment and those for the dentists who did not, we found that many of the dentists who did not provide implant treatment opted for observation or medication, while those who provided implant treatment also implemented removal of superstructure, retightening of screws, repair and so forth. Conclusions We found that many of the implant troubles encountered by dentists who provided visiting dental care were difficulty in cleaning or peri-implantitis, and that the actions taken against these troubles varied depending on the experience of the dentist performing the implant treatment. Our study also revealed that dentists who provide visiting dental care need to acquire knowledge and skills of implant treatment, to have actions prepared in case they encounter such cases, or to closely coordinate with dentists who specialize in implants.
Expression of VEGF-C and its association with clinicopathological features among patients with gastric cancer undergoing gastric surgery at Tongji medical hospital, China.
Authors: MAWALLA BRIAN , Luo Xiaoxiao , Xianglin Yuan
Published: April 2020

Objectives: Gastric cancer shows epidemiological variability according to geographic locations, these differences have been demonstrated both regionally and within countries. There is no baseline protocol regarding using VEGF-C as tumor marker in local setting therefore it was necessary to conduct this study, the current study conducted to analyze the correlation exists between VEGF-C and clinicopathological parameters in patients with gastric cancer undergoing a surgical procedure at Tongji medical hospital. Results: 161samples analyzed were from Chinese patients who had undergone either palliative or curative surgical procedure between October 2015 and September 2017 at Tongji medical hospital. I mmunohistochemistry was method was used to analyses presence of VEGF-C in tissues. Among 161 gastric cancer patients, 101 (62.7%) gastric samples showed strong VEGF-C expression and 60 (37.3%) gastric samples showed weak VEGF-C expression. Using multivariate logistic regression analysis, tumor grade, invasion of lymph nodes and TNM staging were statistically significantly found to associate with strong expression of VEGF-C. VEGF-C strong expression was significantly seen more in adenocarcinoma of gastric cancer, and Therefore, VEGF-C may be used as a biological marker for assessing the biological characteristics of gastric.
Comparative transcriptome profiling reveals cold stress responsiveness in two contrasting Chinese jujube cultivars
Authors: Zhou Heying , He Ying , Zhu Yongsheng , Li Meiyu , Song Shuang , Bo Wenhao , Li Yingyue , Pang Xiaoming
Published: April 2020

Background: Low temperature is a major factor influencing the growth and development of Chinese jujube (Ziziphus jujuba Mill.) in cold winter and spring. Little is known about the molecular mechanisms enabling jujube to cope with different freezing stress conditions. To elucidate the freezing-related molecular changes, we conducted comparative transcriptome analyses from the cold-sensitive cultivar ‘Dongzao’ and cold-tolerant cultivar ‘Jinsixiaozao’ using RNA-Seq. Results: In our study, more than 20,000 genes were detected at chilling (4°C) and freezing (-10°C, -20°C, -30°C and -40°C) stress between the two cultivars. The numbers of differentially expressed genes (DEGs) between the two cultivars were 1831, 2030, 1993, 1845 and 2137 under the five treatments. Functional enrichment analysis suggested that the metabolic pathway, response to stimulus and catalytic activity were significantly enriched under stronger freezing stress. Among the DEGs, nine participated in the Ca2+ signal pathway, thirty-two were identified to participate in sucrose metabolism, and others were identified to participate in the regulation of ROS, plant hormones and antifreeze proteins. In addition, important transcription factors (WRKY, AP2/ERF, NAC and bZIP) participating in freezing stress were activated under different degrees of freezing stress. Conclusions: Our research first provides a more comprehensive understanding of DEGs involved in freezing stress at the transcriptome level in two Z. jujuba cultivars with different freezing tolerances. These results may help to elucidate the molecular mechanism of freezing tolerance in jujube and also provides new insights and candidate genes for genetically enhancing freezing stress tolerance.
Genome-wide genetic structure and selection signatures for color in 10 traditional Chinese yellow-feathered chicken breeds
Authors: Huang Xunhe , Otecko Newton O. , Peng Minsheng , Weng Zhuoxian , Li Weina , Chen Jiebo , Zhong Ming , Zhong Fusheng , Jin Sihua , Geng Zhaoyu , Luo Wei , He Danlin , Ma Cheng , Han Jianlin , Ommeh Sheila C. , Zhang Yaping , Zhang Xiquan , Du Bingwang
Published: April 2020

Background: Yellow-feathered chickens (YFCs) have a long history in China. They are well-known for the nutritional and commercial importance attributable to their yellow color phenotype. Currently, there is a huge paucity in knowledge of the genetic determinants responsible for phenotypic and biochemical properties of these iconic chickens. This study aimed to uncover the genetic structure and the molecular underpinnings of the YFCs trademark coloration.Results: The whole-genomes of 100 YFCs from 10 major traditional breeds and 10 Huaibei partridge chickens from China were re-sequenced. Comparative population genomics based on autosomal single nucleotide polymorphisms (SNPs) revealed three geographically based clusters among the YFCs. Compared to other Chinese indigenous chicken genomes incorporated from previous studies, a closer genetic proximity within YFC breeds than between YFC breeds and other chicken populations is evident. Through genome-wide scans for selective sweeps, we identified RALY heterogeneous nuclear ribonucleoprotein (RALY), leucine rich repeat containing G protein-coupled receptor 4 (LGR4), solute carrier family 23 member 2 (SLC23A2), and solute carrier family 2 member 14 (SLC2A14), besides the classical beta-carotene dioxygenase 2 (BCDO2), as major candidates pigment determining genes in the YFCs.Conclusion: We provide the first comprehensive genomic data of the YFCs. Our analyses show phylogeographical patterns among the YFCs and potential candidate genes giving rise to the yellow color trait of the YFCs. This study lays the foundation for further research on the genome-phenotype cross-talks that define important poultry traits and for formulating genetic breeding and conservation strategies for the YFCs.
Emodin alleviates LPS-induced inflammatory response in lung injury rat by affecting the function of neutrophils
Authors: Mei Hongxia , Tao Ying , Zhang Tianhao , Qi Feng
Published: April 2020

Background: Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are critical life-threatening syndromes characterized by the infiltration of a large number of neutrophils that lead to an excessive inflammatory response. Emodin (Emo) is a naturally occurring anthraquinone derivative and an active ingredient of Chinese medicine. It is believed to have anti-inflammatory effects. In this study, we examined the impact of Emo on the pulmonary inflammatory response and the neutrophil function in a rat model of lipopolysaccharide (LPS)-induced ALI.Results: Treatment with Emo protected rat against LPS-induced ALI. Compared to untreated rat, Emo-treated rat exhibited significantly ameliorated lung pathological changes and decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). However, Emo has no protective effect on the rat model of acute lung injury with neutrophil deficiency. In addition, treatment with Emo enhanced the bactericidal capacity of LPS-induced neutrophils via the up-regulation of the ability of neutrophils to phagocytize bacteria and generate neutrophil extracellular traps (NETs). Emo also downregulated the neutrophil respiratory burst and the expression of reactive oxygen species (ROS) in LPS-stimulated neutrophils, alleviating the damage of neutrophils to surrounding tissues. Finally, Emo can accelerate the resolution of inflammation by promoting apoptosis of neutrophils. Conclusion: Our results provide the evidence that Emo could ameliorates LPS-induced ALI via its anti-inflammatory action by modulating the function of neutrophils. Emo may be a promising preventive and therapeutic agent in the treatment of ALI.
How to recover from a bad start: size at metamorphosis affects growth and survival in a tropical amphibian
Authors: Szekely Diana , Cogalniceanu Dan , Szekely Paul , Armijos-Ojeda Diego , Espinosa-Mogrovejo Valentina , Denoel Mathieu
Published: April 2020

Background: In species with complex life cycles, size at metamorphosis is a key life-history trait which reflects the complex interactions between costs and benefits of life in the aquatic and terrestrial environments. Whereas the effects of a deteriorating larval habitat (e.g. pond desiccation) on triggering an early metamorphosis have been extensively investigated in amphibians, the consequences of the resulting reduced size at metamorphosis on fitness in the post-metamorphic terrestrial stage remain poorly understood. We tested the hypothesis that a smaller size at metamorphosis negatively affects performance and survival in the ensuing terrestrial stage. Using as model a tropical amphibian (Ceratophrys stolzmanni) showing a large phenotypic plasticity in metamorphosing traits, we evaluated the effects of size at metamorphosis on fitness-related trophic and locomotor performance traits, as well as on growth and survival rates. Results: Our results support the hypothesis that a larger size at metamorphosis is correlated with better survival and performance. The survival rate of large metamorphosing individuals was 95%, compared to 60% for those completing metamorphosis at a small size. Locomotor performance and gape size were positively correlated with body size, larger animals being more mobile and capable to ingest larger prey. However, smaller individuals achieved higher growth rates, thus reducing the size gap. Conclusions: Overall, size at metamorphosis affected profoundly the chances of survival in the short term, but smaller surviving individuals partly compensated their initial disadvantages by increasing growth rates.
Adjunct use of mouth rinses with a sonic toothbrush accelerates the detachment of a Streptococcus mutans biofilm: an in vitro study
Authors: Ohsumi Tatsuya , Takenaka Shoji , Sakaue Yuuki , Suzuki Yuki , Nagata Ryoko , Hasegawa Taisuke , Ohshima Hayato , Terao Yutaka , Noiri Yuichiro
Published: April 2020

Background: The aim of this in vitro study was to examine the possible enhancement of the biofilm peeling effect of a sonic toothbrush following the use of an antimicrobial mouth rinse.Methods: The biofilm at a noncontact site in the interdental area was treated by sound wave convection with the test solution or by immersion in the solution. The biofilm peeling effect was evaluated by determining the bacterial counts and performing morphological observations. A Streptococcus mutans biofilm was allowed to develop on composite resin discs by cultivation with stirring at 50 rpm for 72 hours. The specimens were then placed in recesses located between plastic teeth and divided into an immersion group and a combination group. The immersion group was treated with phosphate buffer, Peridex™ mouth rinse or Listerine® mouth rinse. The combination group was treated with Peridex™ or Listerine® and a sonic toothbrush.Results: The biofilm thickness was reduced by approximately one-half compared with the control group. The combination treatment produced a 1 log reduction in the number of bacteria compared to the Listerine® immersion treatment. No significant difference was observed in the biofilm peeling effect of the immersion group compared to the control group.Conclusions: The combined use of a sonic toothbrush and a mouth rinse enhanced the peeling of the biofilm that proliferates in places that are difficult to reach using mechanical stress.
Serum Fetuin-A levels are increased and associated with insulin resistance in women with polycystic ovary syndrome
Authors: Liu Sha , Hu Wenjing , He Yirui , Li Ling , Liu Hua , Gao Lin , Yang Gangyi , Liao Xin
Published: April 2020

Background: Insulin resistance (IR) is a common characteristic of women with polycystic ovary syndrome (PCOS). It has been reported that circulating Fetuin-A levels were associated with IR and type 2 diabetes mellitus (T2DM). However, previous reports were inconsistent. Methods: 207 subjects were screened for PCOS according to the diagnostic guideline of the Rotterdam consensus criterion. Serum Fetuin-A levels were measured using an ELISA kit. An independent t- test or Nonparametric test was used to detect differences between PCOS and control groups.Spearman’s correlation analysis was used to examine the association of the serum Fetuin-A with other parameters. Results: Our findings showed that circulating Fetuin-A concentration ranged from 196.6 to 418.2 µg/L for most women without PCOS (95 %). Women with PCOS had higher circulating Fetuin-A levels than healthy women (437.9 ± 119.3 vs. 313.8 ± 60.5 μg/L; p < 0.01). Serum Fetuin-A was positively correlated with BMI, WHR, TG, TC, LDL-C, HOMA-IR, LH, T, and DHEA-S. Multivariate regression analysis showed that WHR, TG, HOMA-IR, and DHEA-S were independent predictors of the levels of circulating Fetuin-A. Binary logistic regression revealed that serum Fetuin-A was associated with the occurrence of PCOS. In addition, our ROC curve analysis found that the cutoff values for Fetuin-A to predict PCOS and IR were 366.3 and 412.6 µg/L. Conclusion: Blood Fetuin-A may be a useful biomarker for screening women for PCOS and IR.
Osteopontin promoter polymorphisms and risk of urolithiasis: a candidate gene association and meta-analysis study
Authors: Amar Ali , Afzal Ayesha , Hameed Athar , Ahmad Mumtaz , Khan Abdul Rafay , Najma Humaira , Abid Aiysha , Khaliq Shagufta
Published: April 2020

Background: Urolithiasis is a worldwide urological problem with significant contribution of genetic factors. Pakistan, which resides within the Afro-Asian stone belt, has a high reported prevalence (12%) of urolithiasis. Osteopontin (SPP1) is a urinary macromolecule with a suggested critical role in modulating renal stone formation, genetic polymorphisms of which may determine individual risk of developing urolithiasis. However, results of previous studies regarding SPP1 polymorphisms and susceptibility to urolithiasis have apparent inconsistencies with no data available for local population. Methods: 483 Pakistani subjects, including 235 urolithiasis patients and 248 healthy controls, were genotyped for 6 SPP1 genetic polymorphisms to investigate association with urolithiasis in an indigenous candidate gene association study. Further, a comprehensive meta-analysis following a systematic literature search was also performed to provide evidence based account of any existent association between SPP1 promoter polymorphisms and urolithiasis risk.Results: Three SPP1 promoter polymorphisms, rs2853744:G>T, rs11730582:T>C and rs11439060:delG>G, were found to be significantly associated with risk of urolithiasis in indigenous genetic association study (OR = 3.14; p = 0.006, OR = 1.78; p = 0.006 and OR = 1.60; p = 0.012, respectively). We also observed a 1.68-fold positive association of a tri-allelic haplotype of these SPP1 promoter polymorphisms (G-C-dG) with risk of urolithiasis (OR = 1.68; p = 0.0079). However, no association was evident when data were stratified according to gender, age at first presentation, stone recurrence, family history of urolithiasis, parental consanguinity and stone multiplicity. The overall results from meta-analysis, which included 4 studies, suggested a significant association of SPP1 rs2853744:G>T polymorphism with susceptibility of urolithiasis (OR = 1.37; p = 0.004), but not for other SPP1 polymorphic variants analyzed. Conclusions: In conclusion, we report significant association of 3 SPP1 polymorphisms with urolithiasis for the first time from South Asia, however, this association persisted only for SPP1 rs2853744:G>T polymorphism after meta-analysis of pooled studies. Further studies with a larger sample size will be required to validate this association and assess any potential usefulness in diagnosis and prognosis of renal stone disease.