bluuebunny/crossref_metadata_2025 huggingface dataset:
In-depth immune cellular profiling reveals sex-specific associations with frailty
Authors: Samson Leonard Daniël , Boots A. Mieke H. , Ferreira José A. , Picavet H. Susan J. , de Rond Lia G. H. , de Zeeuw-Brouwer Mary-lène , Verschuren W. M. Monique , Buisman Anne-Marie , Engelfriet Peter
Published: January 2020

Background: With advancing age, the composition of leukocyte subpopulations in peripheral blood is known to change, but how this change differs between men and women and how it relates to frailty is poorly understood. Thus, our aim in this exploratory study was to investigate whether frailty is associated with changes in immune cell subpopulations and whether associations differed between men and women. Therefore, we performed in-depth immune cell phenotyping by enumerating subsets of T cells, B cells, NK cells, monocytes, and neutrophils in peripheral blood of 289 elderly people between 60-87 years of age. Associations between frailty and each immune cell subpopulation were tested separately in men and women and were adjusted for age and CMV serostatus. In addition, a random forest algorithm was used to predict a participant’s frailty score based on enumeration of immune cell subpopulations. Results: Frailty was observed to be associated with numerical increases in neutrophils in men and in women. Furthermore, sex-specific associations were found with frailer men, but not women, showing higher numbers of non-classical monocytes and transitional B cells. In addition, frailer women, but not men, showed higher numbers of classical monocytes and lower numbers of NK-T cells. Interestingly, we did not detect an association between frailty and late differentiated memory T-cell subsets. Although the accuracy of the predictions of frailty from information on the immune subpopulations was low (10.7% explained variance in men and 10.5% in women), the prediction model confirmed our findings in the association study. Conclusions: We here report on observed associations of frailty with elevated neutrophil numbers, but not with late stage memory T cell subsets. Furthermore, in-depth immune cellular profiling revealed sex specific associations of frailty with several immune subpopulations. We hope that our study will prompt further investigation into the immune mechanisms associated with the development of frailty in men and women.
Proteomic analysis of human synovial fluid reveals potential diagnostic biomarkers for ankylosing spondylitis
Authors: Lee Ji Hyun , Jung Jae Hun , Kim Jeesoo , Baek Won-Ki , Rhee Jinseol , Kim Tae-Hwan , Kim Sang-Hyon , Kim Kwang Pyo , Kim Jong-Seo , Son Chang-Nam
Published: January 2020

Background Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease affecting the axial skeleton and peripheral joints. The etiology of this disease remains poorly understood, but interactions between genetic and environmental factors have been implicated. The present study identified differentially expressed proteins in the synovial fluid (SF) of AS patients to elucidate the underlying cause of AS. Methods A cohort of 40 SF samples from 10 AS and 10 each of rheumatoid arthritis (RA), gout, and osteoarthritis (OA) patients were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins specific to AS. The label-free LC-MS/MS results were verified by western blotting. Results We identified 8 proteins that were >1.5-fold upregulated in the SF of AS patients compared to that of the disease control groups, including HP, MMP1, MMP3, serum amyloid P-component (APCS), complement factor H-related protein 5 (CFHR5), mannose-binding lectin 2 (MBL2), complement component C9 (C9), and complement C4-A (C4A). CFHR5 and C9 were previously found in serum from AS patients, while APCS was previously found in SF as well as in serum. However, the present study has identified C4A, and MBL2 as potential AS biomarkers for the first time. The expression levels of MMP3, C9, and CFHR5 were verified in AS SF using western blotting. Conclusion We performed quantitative comparative proteomic analysis using by LC-MS/MS of the SF from four disease states: RA, gout, and OA. This systematic comparison revealed novel differentially expressed proteins in AS SF, as well as two previously reported candidate biomarkers. We further verified the expression of MMP3, C9 and CFHR5 by western blot. These proteins may serve as diagnostic or prognostic biomarkers in patients with AS, and may thus improve the clinical outcomes of this serious disease.
Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex
Authors: Mandell Kira Perzel , Price Amanda , Wilton Richard , Collado-Torres Leonardo , Tao Ran , Eagles Nicholas , Szalay Alexander , Hyde Thomas , Weinberger Daniel , Kleinman Joel , Jaffe Andrew
Published: January 2020

Background: DNA methylation (DNAm) is a key epigenetic regulator of gene expression across development. The developing prenatal brain is a highly dynamic tissue, but our understanding of key drivers of epigenetic variability across development is limited. Results: We therefore assessed genomic methylation at over 39 million sites in the prenatal cortex using whole genome bisulfite sequencing and found loci and regions in which methylation levels are dynamic across development. We saw that DNAm at these loci was associated with nearby gene expression and enriched for enhancer chromatin states in prenatal brain tissue. Additionally, these loci were enriched for genes associated with psychiatric disorders and genes involved with neurogenesis. We also found autosomal differences in DNAm between the sexes during prenatal development, though these have less clear functional consequences. We lastly confirmed that the dynamic methylation at this critical period is specifically CpG methylation, with very low levels of CpH methylation. Conclusion: Our findings provide detailed insight into prenatal brain development as well as clues to the pathogenesis of psychiatric traits seen later in life.
Mobile Emergency Care Service For Pregnant Adolescents: A Population-Based Study
Authors: de Freitas Cijara Leonice , EleutérioJr. José , Gonçalves Ana K.
Published: January 2020

Background MECS (Mobile Emergency Care Services) are used worldwide as an effective means to increase the chances of good prognosis in emergency cases, working with anything from trauma cases to unusual risk situations; they enablea reduction in mortality ratesand length of hospital stay. This study aimed to investigate obstetric occurrences in adolescents performed by MECS. Methods This is a population-based study with 352 adolescent pregnant women (10 - 19 years old) treated by the public emergency mobile care system in a medium-sized city, Brazil. Descriptive analysis was performed using measurements of central tendency and dispersion of the numerical variables and the categorical variables, and using these measurements the frequency of occurrences was verified. Additionally, a two-stage cluster analysis was performed to identify divisions in the starting group based on the obstetric characteristics of pregnant women. Results The prevalence of occurrences with adolescents was 28%, corresponding to 352 of the 1258 pregnant women. Among the services provided to pregnant women, the average age of the patients was 17 yearsold (± 1.53). The cluster analysis identified a segmentation of the sample divided into two groups, the first consisting of adolescents with gestational age (GA) over 36 weeks and presenting as main complaints: childbirth, inter-hospital transfer and hypertensive syndromes; and the second composed of patients with less than 36 weeks of GA who complained of hemorrhagic syndromes, premature birth and lower abdominal pain. Conclusion MECS enable adequate and prompt care, which can reduce the consequences of complications for adolescent pregnant women and their babies, reducing mortality rates in developing countries.
A Novel Rind Puncture Technique to Measure Rind Thickness and Diameter in Plant Stalks
Authors: Seegmiller Will H , Graves Jadzia , Robertson Daniel J
Published: January 2020

Background Measurements of rind / culm thickness and stem radius / diameter are important to biomechanical, ecological and physiological plant studies. However, many methods of measuring rind thickness and diameter are labor intensive and induce plant fatality. A novel rind puncture methodology for obtaining measurements of rind thickness and diameter has been developed. The suitability of the new method for implementation in plant studies is presented. Results The novel rind puncture technique was used to obtain measurements of rind thickness and diameter for samples of Poison Hemlock (Conium maculatum). The rind puncture measurements were strongly correlated with caliper measurements (R 2 > 0.97) and photographic image analysis measurements (R 2 > 0.84). The capacity for high throughput measurements using the rind puncture technique was determined to exceed that of caliper measurements and image analysis techniques. Conclusions The rind puncture technique shows promise as a high throughput method for determining rind thickness and diameter as it is cost effective and non-lethal. The authors are currently working to develop a custom handheld apparatus to allow the novel rind puncture method to be used in field work.
A rapid and simple method for routine determination of antibiotic sensitivity to biofilm populations of Pseudomonas aeruginosa
Authors: Wannigama Dhammika Leshan , Hurst Cameron , Hongsing Parichart , Pearson Lachlan , Saethang Thammakorn , Chantaravisoot Naphat , Singkham-in Uthaibhorn , Luk-in Sirirat , Storer Robin James , Chatsuwan Tanittha
Published: January 2020

Treatment of infections of Pseudomonas aeruginosa forming biofilms after antimicrobial testing on planktonic bacteria can result in substantial failure. Therefore, we offer a robust and simple experimental platform to test the impact of antimicrobials on biofilms. Antibiotic response patterns varied uniquely within biofilm formation capacity and minimal biofilm eradication concentrations (MBECs) has a significantly better discriminatory power than minimum inhibitory concentrations (MICs) to differentiate the overall efficiency of antibiotics to eradicate biofilm. Our resazurin-based 96-well-plate platform is able to emulate bacterial responses to antibiotics under biofilm conditions in a fast, simple, and cost-effective screening method adaptable to automation, and warrants trials in the clinic.
A comparison of the Indian Diet with the EAT-Lancet Reference Diet
Authors: Sharma Manika , Kishore Avinash , Roy Devesh
Published: January 2020

Background The 2019 EAT-Lancet Commission report recommends healthy diets that can feed 10 billion people by 2050 from environmentally sustainable food systems. This study compares food consumption patterns in India, from different income groups and regions and sectors(rural/urban), with the EAT-Lancet reference diet and highlights the deviations.Methods The analysis was done using data from consumption expenditure survey of a nationally representative sample of 0.102 million households from 7469 villages and 5268 urban blocks of India by the National Sample Survey Organization (NSSO) in 2011-12. This is the most recent nationally representative data on household consumption in India. Calorie intake (kcal/capita/day) of food groups was calculated using quantity of consumption and nutritional values of food items from the NSSO report. Diet across rural and urban, poor and rich households across different regions were compared with EAT-Lancet reference diet.Results Average daily calorie consumption in India is below the recommended 2503 kcal/capita/day across all groups compared, except for the richest 5% of the population. Calorie share of whole grains is significantly higher than the EAT-Lancet recommendations while those of fruits, vegetables, legumes, and meat, fish & eggs are significantly lower. The share of calories from protein sources is only 6-8% in India compared to 29% in the reference diet. The imbalance is highest for the households in the lowest decile of consumption expenditure, but even the richest households in India do not consume adequate amounts of fruits, vegetables and non-cereal proteins in their diets. An average Indian household consumes more calories from processed foods than fruits.Conclusions Indian diets, across states and income groups, are unhealthy. Indians also consume excessive cereals and not enough proteins, fruits and vegetables. Importantly, unlike many countries, excess consumption of animal protein is not a problem in India. Indian policy-makers need to accelerate food system wide efforts to make healthier and sustainable diets more affordable, accessible and acceptable.
Comparison of three methods for calculation of sacroiliac joint index in different age groups in bone scintigraphy
Authors: Salmanoglu Ebru
Published: January 2020

BackgroundIt was aimed to compare three methods for calculation of sacroiliac joint (SIJ) index in different age groups. Cases undergone Tc-99m MDP bone scintigraphy and images were evaluated. Cases don’t have pathologic uptake were performed posterior pelvic images for calculation of SIJ index.Normal cases (n:160) were included.Cases were separated into four age groups, group 1(3-20 years), group 2(21-40 years), group 3(41-60 years), group 4(61 years and older). For the first method,irregular region of interest (ROI) was selected,for the second method rectangular ROI was selected.For the third method, profile peak counts were used. Count of each SIJ was divided count of sacrum to calculate right, left and mean SIJ indices.ResultsThere was no statistically significant difference between mean values of right and left SIJ index for three methods(p>0.05).Means of female were lower than male for right, left and and mean SIJ indices.Lowest mean values of right SIJ index, left SIJ index and mean SIJ index were found in ≥61 age group in both genders.All of three methods were significantly different from each other according to four age groups(p<0.05). First method had quite lower mean value than second and third methods for right SIJ index.A negative statistically significant correlation was found between age and SIJ index for all of three methods(p<0.01). Statistically significant difference was found between three methods for each age gropus based on mean SIJ index(p<0.05).ConclusionsEach nuclear medicine center should establish their own threshold value according to their own data set in normal cases and patients.
Oncology and functional prognosis are both vital in the surgical treatment of RGCTs around the knee joint
Authors: Liu Qing , He Hongbo , Hao Zeng , Liu Yupeng , Zhang Can , Luo Wei
Published: January 2020

Aims To explore and provide reasonable surgical options for recurrent giant cell tumors of bone (RGCTs) around the knee joint and compare the pros and cons of extended curettage (EC) and segmental resection (SR). Materials and Methods A retrospective analysis was performed of 22 patients (11 male, 11 female; mean age, 34.1 years) with RGCT around the knee joint treated in our hospital between June 2007 and June 2017. Average recurrence time was 14.2 ± 4.7 months. Basic clinical data, including Campanacci grade, lesion location, filler materials, pathological fracture, were recorded. Based on different reoperation methods, patients were divided into the EC and SR groups. Patients were regularly followed up; and recurrence, metastasis, local complications such as osteoarthritis, infection, prosthesis loosening, were recorded. Patient function and surgical efficacy were evaluated using the musculoskeletal tumor society (MSTS) score and Mankin score, respectively. Results Postoperative recurrence occurred in one patient in both groups, and no difference in the prognosis of oncology was observed between the groups. In the EC group, seven patients developed postoperative complications, but required no surgical treatment, whereas in the SR group, five patients developed postoperative complications and surgical treatment was performed on two patients. There were significant differences in the functional prognosis and surgical efficacy between the two groups; however, the EC group showed more satisfactory results. Conclusion The oncological and functional prognosis of patients with RGCT around the knee joint is vital. EC should be considered as the first-line treatment, unless the tumors severely invade the surrounding soft tissues or are accompanied by complex fractures with significant displacement leading to no surgical curettage boundary.
miR-132 is up-regulated in polycystic ovarian syndrome and inhibits granulosa cells proliferation via targeting Foxa1
Authors: Cui Xiangrong , Jing Xuan , Liu Junfen , Yan Meiqin , Bi Xingyu , Wu Xueqing
Published: January 2020

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders characterized by hyperandrogenism, polycystic ovaries and ovulatory dysfunction. Several studies have suggested that the aberrant expression of miRNAs serves an important role in the pathogenesis of PCOS, though the role and underling mechanism of microRNA-132 (miR-132) in the development of PCOS remain unclear. Methods: The expression of miR-132 in granulosa cells (GCs) derived from 26 PCOS patients and 30 healthy controls was detected through RT-qPCR. And the apoptosis levels of granulosa cells were measured by TUNEL.Granulosa-like tumor cell line (KGN) was cultured for cell counting kit-8 (CCK-8) was assays after over-expression of miR-132 or knockdown TargetScan was applied to analysis the potential targets of miR-132, which was further verified by luciferase assay, RT-qPCR and western blot. Results: The expression of miR-132 was declined in granulosa cells of PCOS patients. Meanwhile, the significantly increased apoptotic nuclei were present GCs of PCOS patients. Furthermore, over-expressed of miR-132 inhibited the proliferation of KCN cells. In addition, our results verified that miR-132 directly targeted Foxa1, knockdown of which suppressed KGN cells proliferation. Conclusion: Our results revealed that miR-132 inhibits the cell viability and induces apoptosis by directly interacting with Foxa1, indicating a role of miR-132 to be a potential target in the PCOS patients.
Sentiment Analysis of Online Product Reviews Using DLMNN and Future Prediction of Online Product Using IANFIS
Authors: p Sasikala , Sheela Mary Immaculate
Published: January 2020

Sentiment analysis or opinion mining is one of the major tasks of NLP (Natural Language Processing). It captures the user’s opinion, feelings, and belief regarding the respective product especially to determine whether the user’s attitude is positive, negative, or neutral. This analysis greatly helps the companies to make necessary changes in their product which in return can overcome the flaws that the product is facing and targets better customer satisfaction. Existing techniques for the sentiment analysis of online product reviews obtained low accuracy and also took more time for training. To overcome such issues in this paper, a DLMNN is proposed for sentiment analysis of online product review and IANFIS is proposed for future prediction of online product. Here, the sentiment analysis and future predictions are done on the products taken from the food review dataset. First, from the dataset, the data values are partitioned into GB, CB, and CLB scenarios and then the review analysis for each scenario is performed separately using DLMNN and they give the result as positive, negative, and neutral reviews for the product. After the process of review classification based on these three scenarios, the future prediction of the products is done by performing weighting factor and classification using IANFIS. Experimental results are compared with some existing techniques and the results show that the proposed method outperforms other existing algorithms.
Incidence and predictors of mortality among children admitted to the pediatric intensive care unit at the University of Gondar comprehensive specialized hospital, northwest Ethiopia: A prospective observational cohort study
Authors: Teshager Nahom Worku , Amare Ashenafi Tazebew , Tamirat koku
Published: January 2020

Background Pediatric intensive care unit (PICU) tremendously improves the success of saving patients having potentially life-threatening illness. An accurate estimate of lives saved through pediatric critical care intervention is important to evaluate the quality of the health care system. Data on pediatric critical care in developing countries remain scarce yet is much needed to improve clinical practices and outcomes. This study aimed to determine the incidence and predictors of mortality in the pediatric intensive care unit in the study setting.Method An institution based prospective cohort study was conducted from February 2018 to July 2019. We collected data by interview, chart and registration book review. Life table was used to estimate the cumulative survival of patients and Log rank test was used to compare survival curves between different categories of the explanatory variables. Survival trend over the follow up time was described using the Kaplan Meier graph. Bivariate and multivariate Cox proportional hazard model were used to identify predictors.Result Based on the 10 th version of international classifications of disease (ICD) of WHO, neurologic disorders (22.7%) infectious disease (18.8%) and environmental hazards (11.8%) account for the top three diagnoses. The median observation time was 3 days with IQR of 1 to 6 days. Of the total of 313 participants, 102 (32.6%) died during the follow-up time. This gives the incidence of mortality of 6.9 deaths per 100 person day observation. Caregivers’ occupation of government-employed (AHR=0.35, 95%CI: 0.14, 0.89), weekend admission (AHR=1.63, 95%CI: 1.02, 2.62), critical illness (AHR=1.79, 95%CI: 1.13, 2.85) Mechanical ventilation AHR=2.36,95%CI: 1.39, 4.01)and PIM2 score (AHR=1.53, 95%CI: 1.36, 1.72) were predictors of mortality in the pediatric ICU.Conclusion Neurologic disorder was the leading causes of admission followed by infectious diseases, and environmental hazards. Rate of mortality was high and admission over weekends, caregivers' occupation, mechanical ventilation, critical illness diagnosis, and higher PIM2 scores were found to be significant and independent predictors of mortality at the PICU. This suggests that ICU medical equipment, diagnostics, and interventions should be available up to the standard. Intensivist and full staffing around the clock has to be available in the PICU.
Clinical course after identification of new-onset atrial fibrillation in critically ill patients: a multicenter prospective cohort study
Authors: Yoshida Takuo , Uchino Shigehiko , Sasabuchi Yusuke
Published: January 2020

BackgroundNew-onset atrial fibrillation (AF) in critically ill patients is reportedly associated with poor outcomes. However, epidemiological data in intensive care units (ICUs) after new-onset AF identification are lacking. This study aimed to describe the clinical course after the identification of new-onset atrial fibrillation.Methods This prospective cohort study of 32 ICUs in Japan during 2017-2018 enrolled adult patients with new-onset AF. We collected data on patient comorbidities, physiological information before and at the AF onset, interventions, transition of cardiac rhythms, adverse events, and in-hospital death and stroke.Results The incidence of new-onset AF in the ICU was 2.9% (423 patients). At the AF onset, the mean atrial pressure decreased, and the heart rate increased. Sinus rhythm returned spontaneously in 84 patients (20%), and 328 patients (78%) were treated with pharmacological interventions (rate-control drugs, 67%; rhythm-control drugs, 34%). In total, 173 (40%) patients were treated with anticoagulants. Adverse events were more frequent in nonsurvivors than in survivors (bleeding: 14% vs 5%; p = 0.002, arrythmia other than AF: 6% vs 2%; p = 0.048). There were 92 (22%) and 15 patients (4%) patients who continued to have AF at 48 hours and 168 hours after onset, respectively. The hospital mortality rate of those patients were 32% and 60%, respectively. The overall hospital mortality was 26%, and the incidence of in-hospital stroke was 4.5%.Conclusions Although the proportion of patients continued to have AF within 168 hours decreased with various treatments, these patients were at a high risk of death. Moreover, adverse events occurred more frequently in nonsurvivors than in survivors. Further research to assess the management of new-onset AF in critically ill patients is strongly warranted.
Effect of Diabetes Mellitus on Survival in Patients with Gallbladder Cancer: A Systematic Review and Meta-analysis
Authors: Jing Chen , Wang Zhengyi , Fu Xue
Published: January 2020

Background Increasing evidences indicate that diabetes may increase the incidence of gallbladder cancer. However, no sufficient data clarify the effect of diabetes on survival in patients with gallbladder cancer.Methods We comprehensively search PubMed, Embase, and the Cochrane Library databases through July 2019 in order to find sufficient eligible researches. The pooled hazard risks (HRs) and relative risks (RRs) with 95% confidence intervals (CIs) were calculated with either fix-effects or random-effects model.Results Ten eligible studies were included in this meta-analysis. Analysis of eight cohorts found that diabetes was closely associated with the mortality of gallbladder cancer (HR=1.10; 95% CI: 1.06-1.14; P<0.00001). However, no significant differences were found between male and female diabetes patients (RR=1.08, 95%CI=0.57-2.04, P=0.80).Conclusions These findings indicate that diabetes patients have a higher mortality of gallbladder cancer compared with non-diabetes and general population.
Association of glial and neuronal degeneration markers with Alzheimer‘s disease cerebrospinal fluid profile and cognitive functions
Authors: Teitsdottir Unnur D. , Jonsdottir Maria K. , Lund Sigrun H. , Darreh-Shori Taher , Snaedal Jon , Petersen Petur H.
Published: January 2020

Background Neuroinflammation has gained increasing attention as a potential contributing factor in the onset and progression of Alzheimer‘s disease (AD). The objective of this study was to examine the association of selected cerebrospinal fluid (CSF) inflammatory and neuronal degeneration markers with signature CSF AD profile and cognitive functions among subjects at the symptomatic pre- and early dementia stages.Methods In this cross-sectional study, 52 subjects were selected from an Icelandic memory clinic cohort. Subjects were classified as having CSF AD (n=28, age=67, 33% female, Mini-mental state examination [MMSE]=28) or non-AD (n=24, age=70, 39% female, MMSE=27) profile based on the ratio between CSF total-tau (T-tau) and amyloid-β 1‐42 (Aβ 42 ) values (cut-off point chosen as 0.52). Novel CSF biomarkers included Neurofilament light (NFL), YKL-40, S100 calcium-binding protein B (S100B) and Glial fibrillary acidic protein (GFAP), measured with enzyme-linked immunosorbent assay (ELISA). Subjects underwent a neuropsychological assessment for evaluation of different cognitive domains including verbal episodic memory, non-verbal memory, language, processing speed and executive functions.Results Accuracy for distinguishing between the two CSF profiles was calculated for each CSF marker and cognitive domain. Verbal episodic memory performed the best overall (Area under curve [AUC]=0.80), with AUCs for CSF markers ranging from 0.61 to 0.64. For estimation of the relationships between CSF markers and cognitive domains (adjusted for age and education), Pearson‘s correlation and ridge regression analyses were performed. The ratio between NFL and YKL-40 levels correlated higher with verbal episodic memory score (r=-0.51, p <0.001) compared to single protein levels (NFL: r=-0.26, p =0.06; YKL-40: r=0.18, p =0.20). The correlation was also higher among those with CSF AD profile (r=-0.67, p <0.001) compared to those without (r=-0.46, p =0.03). GFAP levels showed weak correlation with executive functions scores (r=-0.37, p =0.007). Among those with a CSF AD profile, both S100B (r=-0.45, p =0.02) and GFAP (0.68, p <0.001) levels correlated with processing speed scores.ConclusionsThe novel CSF markers NFL, YKL-40 and GFAP show potential as markers for cognitive decline among individuals with core AD pathology at the symptomatic pre- and early stages of dementia.
Insect Repellents Mediate Species-Specific Olfactory Behaviors in Mosquitoes
Authors: Afify Ali , Potter Christopher John
Published: January 2020

Background: The species-specific mode of action for DEET and many other mosquito repellents is often unclear. Confusion may arise for many reasons. First, the response of a single mosquito species is often used to represent all mosquito species. Second, behavioral studies usually test the effect of repellents on mosquito attraction towards human odorants, rather than their direct repulsive effect on mosquitoes. Third, the mosquito sensory neuron responses towards repellents are often not directly examined.Methods: Here, we used a close proximity response assay to test the direct repulsive effect of six mosquito repellents on Anopheles coluzzii, Aedes aegypti, and Culex quinquefasciatus mosquitoes. Additionally, we used this behavioral assay and calcium imaging recordings of antennae to test the response of An. coluzzii mosquitoes towards two human odorants (1-octen-3-ol and benzaldehyde) at different concentrations, and mixtures of the repellents lemongrass oil and p-menthane-3,8-diol (PMD) with DEET.Results: We found that An. coluzzii mosquitoes were repelled by lemongrass oil and PMD, while Ae. aegypti and Cx. Quinquefasciatus mosquitoes were repelled by lemongrass oil, PMD, eugenol, and DEET. In addition, we found that high concentrations of 1-octen-3-ol and benzaldehyde were repellent, and activated more olfactory receptor neurons on the An. coluzzii antenna than lower concentrations. Finally, we found that changes in olfactory responses to repellent mixtures reflected changes in repulsive behaviors.Conclusions: Our findings suggest that different species of mosquitoes have different behavioral responses to repellents. We further suggest that high-odor concentrations may recruit repellent-sensing neurons, or generally excite many olfactory neurons, yielding repellent behavioral responses. Finally, we show that DEET can decrease the neuronal and behavioral response of An. coluzzii mosquitoes towards PMD but not towards lemongrass oil. Overall, these studies can help inform mosquito repellent choice by species, guide decisions on effective repellent blends, and could ultimately identify the olfactory neurons and receptors in mosquitoes that mediate repellency.
Antimalarial activity of traditional Kampo medicine Coptis Rhizome extract and its major active compounds
Authors: Teklemichael Awet Alem , Mizukami Shusaku , Toume Kazufumi , Mosaddeque Farhana , Kamel Mohamed Gomaa , Kaneko Osamu , Komatsu Katsuko , Karbwang Juntra , Huy Nguyen Tien , Hirayama Kenji
Published: January 2020

Background: The herbal medicine has been an attractive source of new antimalarial drugs exemplified by quinine and artemisinin, thus we examined a variety of Japanese traditional herbal medicine (Kampo) for their potential antimalarial activities.Methods: We designed a comprehensive screening to identify novel antimalarial drugs from a library of Kampo crude drug extracts (n = 120). The antimalarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and -resistant (Dd2) strains of Plasmodium falciparum. The cytotoxicity was also evaluated using primary Adult Mouse Brain cells. Subsequently, major active components of Kampo crude drug extracts showing high antimalarial activities and low cytotoxicity were further evaluated. Finally, the in vivo antimalarial activities of promising Kampo crude drug extract was investigated using P. yoelii infected mouse model in a seven-day suppressive test (treatment start two hours after challenge infection and continue for seven days).Results: Out of 120 extracts, Coptis Rhizome showed the highest antimalarial activity (IC50 1.9 µg/mL of 3D7 and 4.85 µg/mL of Dd2) with a high selectivity index (SI) > 263 (3D7) and > 103 (Dd2). Three major components in Coptis Rhizome also showed antimalarial activities with IC50 ranging from 1.1 to 6.0 µM (against 3D7) and from 3.1 to 11.8 µM (against Dd2). Among them, coptisine chloride exhibited the highest antimalarial activity (IC50 1.1 µM against 3D7 and 3.1 µM against Dd2) with SI of 37.8 and 13.2, respectively. Furthermore, Coptis Rhizome exhibited significant antimalarial activity in mice infected with P. yoelii 17X strain with respect to its activity on parasite suppression consistently throughout the entire test period (P < 0.05).Conclusion: Coptis Rhizome showed a significant in vivo antimalarial activity in mice infected with P. Yoelii, thus it is a potential natural resource for antimalarials and its component coptisine chloride is a promising antimalarial lead compound.
Thermal effects of monopolar electrosurgery detected by real-time infrared thermography: an experimental appendectomy study
Authors: Nechay Taras , Titkova Svetlana M. , Anurov Mikhail V. , Mikhalchik Elena V. , Melnikov-Makarchyk Kirill Y. , Ivanova Ekaterina A. , Tyagunov Alexander E. , Fingerhut Abe , Sazhin Alexander V.
Published: January 2020

Purposes. Monopolar energy (ME) is routinely used in appendectomy. This study aimed to investigate the degree of lateral thermal spread generated by ME and to evaluate the thermal injury sustained by the close-lying tissues.
Materials and methods. Appendectomy with a monopolar Maryland dissector was performed in 8 rabbits (at 30 and 60 W power settings). A high-resolution infrared camera was used to record tissue heating during the intervention. After autopsy macroscopic changes were evaluated and tissue samples were subjected to myeloperoxidase (MPO) assay and histological examination.
Results. No significant differences in the extent of thermal spread, MPO activity and histological signs of inflammation were observed between groups. Regardless of the power settings, the heat spread exceeded 2 cm laterally along the mesoappendix when application time exceeded 3 s. The spread of heat through tubular structures in both groups caused a significant temperature rise in the nearby intestinal loop, resulting in perforation (n=3) and necrosis (n=1).
Conclusions. Application time is critical in thermal spread during appendectomy aided by ME. Tubular anatomic structures can enhance thermal injury on distant tissues. The observed effects of ME bear clinical relevance that need further investigation.
Real GDP growth rates and health care spending – Comparison between the G7 and the EM7 countries
Authors: Jakovljevic Mihajlo , Timofeyev Yuriy , Ranabhat Chhabi , Fernandes Paula Odete , Teixeira João , Rancic Nemanja , Reshetnikov Vladimir
Published: January 2020

Background: Accelerated globalization has substantially contributed to the rise of emerging markets worldwide. The G7 and Emerging Markets Seven (EM7) behaved in significantly different macroeconomic ways before, during, and after the 2008 Global Financial Crisis. Average real GDP growth rates remained substantially higher among the EM7, while unemployment rates changed their patterns after the crisis. Worldwide economic growth began to accelerate again, starting from year 2017. However, approximately one half of this growth is attributable to the EM7, while only a quarter to the G7 nations. This paper aims to analyse the association between the health spending and real GDP growth in the G7 and the EM7 countries.Results: In terms of GDP growth, the EM7 exhibited higher degree of resilience during the 2008 Global Crisis, compared to the G7. Unemployment in the G7 nations was rising significantly, compared to pre-recession levels, but, in the EM7, it remained traditionally high. In the G7, the austerity (measured as a percentage of GPD and in PPP basis) significantly decreased the public health expenditure, even so in than in the EM7. Out-of-pocket health expenditure grew at far more concerning pace in the EM7 compared to the G7 during the Crisis, exposing vulnerability of citizens and households living close to poverty line. Regression analysis demonstrated that, in the G7, real GDP growth had positive impact on out-of-pocket expenditure measured as a percentage of current health expenditure expressed as a percentage of GDP (CHE). In the EM7, it affected negatively CHE, CHE per capita in PPP in constant 2011 international USD, and out-of-pocket expenditure per capita in PPP international USD. Conclusion: The EM7 countries showed stronger endurance withstanding the consequences of the global economic crisis as compared to the G7 economies. Evidence of that were most visible in real growth rates and unemployment rates, before, during, and after the crisis. It influenced health spending patterns in both groups, although they tended to diverge instead of converging in several important areas.
Gut microbiota and butyrate contribute to nonalcoholic fatty liver disease in premenopause due to estrogen deficiency
Authors: Liu Limin , Qingsong Fu , Tiantian Li , Kai Shao , Xing Zhu , Yingzi Cong , Xiaoyun Zhao
Published: January 2020

Background：The incidence of nonalcoholic fatty liver disease (NAFLD) in postmenopausal women has increased significantly. NAFLD can be effectively inhibited by estrogen, but the severe side effects, especially the increased risk of malignant tumors, limit its application. Thus, it is of great clinical significance to explore the mechanism by which estrogen inhibits NAFLD. Gut microbiota and its metabolites short chain fatty acids (SCFA) have been shown to play important roles in the development of NAFLD.Objective：In this study, we investigated the impact of estrogen deficiency on the gut microbiome and SCFA in both NAFLD patients and an experimental NAFLD model in premenopause.Methods：The levels of estrogen，insulin and leptin was measured using ELISA. Gut microbiota was analyzed by 16S rRNA gene sequence analysis. Tissue sections were stained with hematoxylin and eosin. SCFAs were determined with Agilent 6890 N gas chromatography (GC). We quantified mRNA levels of genes in our study by quantitative real time-PCR. Additionally, Western Blotting was used to validate protein expression.Results：We showed that female NAFLD patients had much lower estrogen levels. Estrogen deficient mice, due to ovariectomy (OVX), suffered more severe liver steatosis with an elevated body weight, abdominal fat weight, and serum triglycerides with deterioration in histological hepatic steatosis. Altered gut microbiota composition and decreased butyrate content were found in patients with NAFLD and in OVX mice. Furthermore, fecal microbiota transplantation (FMT) or supplementing with butyrate markedly alleviated NAFLD in OVX mice. The production of antimicrobial peptides (AMP) RegIIIg, β-defensins 1, 3 and the expression of intestinal epithelial tight junction, including ZO-1 and occludin5, were decreased in the OVX mice compared to control mice. Upregulation of PPAR-ɣ and VLDLR and downregulation of PPAR-ɑ indicated that OVX mice suffered from abnormal lipid metabolism.Conclusions：These data indicate that changes in the gut microbiota and SCFA caused by estrogen reduction, together with a disorder in AMP production and lipid metabolism, promote NAFLD, thus provide microbiota derived SCFAs as new therapeutic targets for the clinical prevention and treatment of NAFLD.
Determinants of Glycemic Control among Urban Patients with Type 2 Diabetes: A mediation analysis from real-world evidence
Authors: Silva-Tinoco Rubén , Cuatecontzi-Xochitiotzi Teresa , Torre-Saldaña Viridiana De la , León-García Enrique , Serna-Alvarado Javier , Orea-Tejeda Arturo , Castillo-Martínez Lilia , Gay Juan G. , de-León David Cantú , Prada Diddier
Published: January 2020

Aims To explore the determinants of glycemic control (GC) among patients with type 2 diabetes (PwD) to provide insight into the pathways of the effect of diabetes knowledge on GC.Methods A multicenter cross-sectional study was conducted in PwD from 28 primary outpatient centers located in Mexico City. Using the multivariable-adjusted models, we determined the associations between diabetes knowledge, self-care behaviors, and glycemic control. The mediation analyses used linear regression models, where the significance of indirect effects was calculated with bootstrapping.Results The population (N=513) had a mean age of 53.8 years (standard deviation: 11.3 yrs.), and 65.9% were women. Using multivariable-adjusted linear models, we found that diabetes knowledge was associated with glycemic control (β: -0.102, 95% Confidence Interval [95% CI] -0.189, -0.014). Diabetes knowledge was also independently associated with self-care behavior (for physical activity: β: 0.181, 95% CI 0.088, 0.273), and self-care behavior was associated with glycemic control (for physical activity: β: -0.112, 95% CI -0.194, -0.029).The association between diabetes knowledge and glycemic control was lost after adjustment for self-care behaviors, especially physical activity (β: -0.084, 95% CI -0.182, 0.014, p -value: 0.062). Finally, the mediation models showed that the effect of diabetes knowledge on glycemic control was 17% independently mediated by physical activity ( p -value: 0.049).Conclusions Self-care activities, particularly physical activity, mediated the effect of diabetes knowledge on glycemic control. Our results indicate that diabetes knowledge should be reinforced in low-income PwD, with an emphasis on the benefits physical activity has on improving GC.
Chronic Exposure to Diesel Exhaust Particulate Matter Impairs Meiotic Progression during Spermatogenesis in a Mouse Model
Authors: Yang Wei , Xu Yanyi , Pan Hongjie , Tian Fang , Wang Yuzhu , Xia Minjie , Hu Jingying , Yang Mingjun , Tao Shimin , Sun Shenfei , Kan Haidong , Li Runsheng , Ying Zhekang , Li Weihua
Published: January 2020

Background: Exposure to air pollutants represented by diesel exhaust PM2.5 (DEP) correlates with the decline of semen quality, but the underlying biological mechanism has not been fully understood. In the present study, mice were intratracheally instilled with DEP for around 7 months, and the effects of PM2.5 exposure on the spermatogenic process as well as the alterations of testicular gene expression profile were assessed. Results: Our results show that chronic exposure to DEP significantly impairs the fertility of male mice without influencing their libido. Compared with Vehicle-exposed group, the sperm count and motility from DEP-exposed mice were significantly decreased. In addition, immunohistological staining of γH2AX and DMC1, biomarkers for meiotic double strand breaks (DSBs), demonstrated that chronic exposure to DEP comprised the repair of meiotic DSBs, thus disrupts the spermatogenesis. Deep RNA sequencing test shows massive altered expressions of testicular genes including the GnRH signaling pathway. Conclusion: In summary, our research demonstrates that chronic exposure to PM2.5 disrupts spermatogenesis through targeting the meiotic recombination, providing a new perspective for the research on the male reproductive system damage caused by air pollution.
Quantitative assessment of neural elements in rat model using nerve growth factor after remnant-preserving anterior cruciate ligament reconstruction: a hematoxylin and eosin stain and immunohistochemical study
Authors: Lee Sung Hyun , Cho Hyung Gyu , Song Jin Soo , Chun Keun Churl , Chun Churl Hong
Published: January 2020

Background: Immunohistochemical analyses of anterior cruciate ligament (ACL) allografts following remnant-preserving ACL reconstructions using Achilles tendon allografts have provided evidence for the presence of neural elements. In this study, we aimed to examine the expression of neural elements and quantify the presence of neural cells in ACL remnants and Achilles allografts using nerve growth factor (NGF) therapy after remnant-preserving ACL reconstruction. Methods: Experiments were conducted on 5 pairs of rats (approximately 8 weeks old and weighting 320 g at the time of surgery). Longitudinally-split Achilles tendons from the paired rats were freshly frozen and later defrosted with warm saline and allografted onto the right ACL of the other, which was partially detached at the femoral attachment site. A sham operation was conducted on the left knee to be used as Control. NGF was injected in both the knee joints 1 week after surgery. The presence of neural cells in the ACL of the sham-operated knee, allografted Achilles tendon, and ACL remnant was examined 6 weeks post surgery using H and E and immunohistochemical staining. Results: H and E staining did not reveal neural cells in any of the three groups. However, immunohistochemical analysis showed the presence of nestin-positive neural elements in normal ACL as well as ACL remnants. Additionally, neural elements were examined in 7 of the 8 (87.5%) allograft tissues. Quantitative analysis showed no difference in the number and area of nuclei among the three groups. However, the number and area of neural cells in Achilles allograft were significantly lower than in the other two groups (p=0.000 and p=0.001, respectively). Conclusion: Our observations indicate that ACL remnants promote new ingrowth and persistence of neural cells. We suggest that the ingrowth of neural elements could support the persistence and new ingrowth of mechanoreceptors, thereby enhancing the functional stability of knee joints. Moreover, the expression of neural cells in Achilles allograft was lower than that of normal ACL or ACL remnants in the quantitative evaluation, thereby confirming the essential role of ACL remnants in knee joint functionalization. Key terms: anterior cruciate ligament, remnant preservation, immunohistochemistry, nerve growth factor