Background Amniotic fluid-derived mesenchymal stromal cells (AFMSCs) are promising stem cells for regeneration medicine. However, AFMSCs isolated at different stages of pregnancy have different biological characteristics, and the therapeutic effects can differ in vivo and in vitro. The mechanisms underlying these differences have not been defined. Methods Bioinformatics analysis of the AFMSC transcriptome identified Chrdl1 as one of the differentially expressed genes. We evaluated the effects of Chrdl1 overexpression or knockdown on the proliferation and migration of AFMSCs. Target prediction was performed using miRanda software to identify the upstream microRNA of Chrdl1. The interaction between Chrdl1 mRNA and its upstream microRNA was evaluated using a dual-luciferase reporter gene assay. Results Chrdl1 was expressed at lower levels in AFMSCs derived from the early stages of pregnancy. It could suppress AFMSC proliferation and migration. miR-532-3p promoted AFMSC proliferation and migration by targeting the 3' UTR of Chrdl1 and downregulating its expression.The roles of the extracellular biophysical environment in cancer are barely studied. This study considers the possibility that cell-like topography of a cancer cell environment may influence chemo-responses. Here, a novel bioimprinting technique was employed to produce cell-like topography on the polystyrene substrates used for cell culture. In this work, we have shown that extracellular biophysical cues generated from the topography alter the chemosensitivity of ovarian cancer cells. The three-dimensionality of the bioimprinted surface altered the cell-surface interaction, which consequently modulated intracellular signalling and chemoresponses. Sensitivity to platinum was altered more than that to paclitaxel. The effect was largely mediated through the integrin/focal adhesion system and the Rho/ROCK pathway. Moreover, the results provided evidence that biophysical cues also modulate MAPK signalling associated with chemo-resistance in ovarian cancer. Therefore, the novel findings from of this study revealed for the first time that the effects of the biophysical environment, such as substrate topography, influences ovarian cancer cell responses to clinical drugs. These observations suggest that a full clinical understanding of ovarian cancer will include biophysical aspects of tumour microenvironment.UC is a chronic inflammatory disease of the colonic mucosa and lacks effective treatments because of unclear pathogenesis. Excessive apoptosis of IECs damages the intestinal epithelial barrier and is involved in the progression of UC, but the mechanism is unknown. HSPs are important in maintaining homeostasis and regulate apoptosis through the mitochondrial pathway. In our previous studies, HSF2, an important regulator of HSPs, was highly expressed in UC patients and negatively correlated with inflammation in mice and IECs. Therefore, we hypothesized that HSF2 may protect against intestinal mucositis by regulating the apoptosis of IECs. In this study, a DSS-induced colitis model of hsf2-/- mice was used to explore the relationship between HSF2 and apoptosis in IECs for the first time. The expression of HSF2 increased in the WT + DSS group compared with that in the WT + H2O group. Moreover, the extent of apoptosis was more severe in the KO + DSS group than in the WT + DSS group. The results showed that HSF2 was negatively correlated with apoptosis in vivo. The expression of HSF2 in Caco-2 cells was changed by lentiviral transfection, and the expression of Bax, cytoplasmic Cyto-C, Cleaved Caspase-9 and Cleaved Caspase-3 were negatively correlated with the different levels of HSF2. These results suggest that HSF2 negatively regulates apoptosis of IECs through the mitochondrial pathway. This may be one of the potential mechanisms to explain the protective role of HSF2 in UC.Human Immunodeficiency Virus (HIV), the etiological agent for Acquired Immunodeficiency Syndrome (AIDS), continues to kill humans despite stupendous advances in antiviral research. With the presently available combination antiretroviral therapeutic arsenal, AIDS is now a manageable disease but with no cure available till date. The development of novel antivirals consumes an extensive amount of time and resources. Hence, repurposing of the established gold standard molecules for their anti-HIV application is enormously advantageous. In this study, we report that N-p-Tosyl-L-phenylalanine chloromethyl ketone (TPCK) inhibits HIV-1 replication in a highly-conserved manner. Further, TPCK inhibits HIV-1 replication at the late stages of its life cycle by impeding viral protease (PR) enzyme activity. Additionally, our results demonstrate that the combination of TPCK with established HIV-1 PR inhibitors shows significant synergistic inhibitory potential, suggesting the potential use of TPCK in cART regimen. Collectively, we report the anti-HIV activity of TPCK, which should be further characterized for its translational applications.Dicarboxylic fatty acids, taken as a nutritional supplement or produced endogenously via omega oxidation of monocarboxylic fatty acids, may have therapeutic potential for rare inborn errors of metabolism as well as common metabolic diseases such as type 2 diabetes. Breakdown of dicarboxylic acids yields acetyl-CoA and succinyl-CoA as products, the latter of which is anaplerotic for the TCA cycle. However, little is known about the metabolic pathways responsible for degradation of dicarboxylic acids. Here, we demonstrated with whole-cell fatty acid oxidation assays that both mitochondria and peroxisomes contribute to dicarboxylic acid degradation. Several mitochondrial acyl-CoA dehydrogenases were tested for activity against dicarboxylyl-CoAs. https://www.selleckchem.com/products/sw-100.html Medium-chain acyl-CoA dehydrogenase (MCAD) exhibited activity with both six and 12 carbon dicarboxylyl-CoAs, and the capacity for dehydrogenation of these substrates was significantly reduced in MCAD knockout mouse liver. However, when dicarboxylic acids were fed to normal mice, the expression of MCAD did not change, while expression of peroxisomal fatty acid oxidation enzymes was greatly upregulated. In conclusion, mitochondrial fatty acid oxidation, and in particular MCAD, contributes to dicarboxylic acid degradation, but feeding dicarboxylic acids induces only the peroxisomal pathway.

© 2020 The Author(s).This paper describes the additional data to our research article "Bacterial line of defense in Dirinaria lichen from two different ecosystems First genomic insights of its mycobiont Diriniria sp. GBRC AP01" by Puvar et al. [1]. In this manuscript we are presenting the data obtained during the annotation of the genome enriched from metagenomic data from the lichen samples. © 2020 The Author(s).This article contains data on the concentration of heavy metals and metalloids in the water of seven rivers in the Mantaro river watershed in the central Andes of Peru, collected during the autumn of 2019. The concentrations of Cu, Fe, Pb, Zn and As were determined by flame atomic absorption spectrophotometry to assess human risk. The concentration of heavy metals and arsenic varied according to the sector of the rivers evaluated. The cluster analysis identified four different groups among the observation sectors. The risk assessment for humans was conducted on the basis of exposure doses to heavy metals and arsenic in water by ingestion and dermal pathways, using standard methods established by USEPA. These data can be reused as a basis for estimating the cancer risk or as a comparison group for future risk studies. They can also be useful to public health policy makers when proposing surveillance and control programmes using remedial technologies. © 2020 The Author(s).In this document, the photocatalytic activity of TiO2/Fe3O4, prepared by the mixing of the pure oxides, was studied. The photocatalytic degradation of aqueous Methylene Blue (MB) solutions (10 and 30 ppm) was performed, the TiO2/Fe3O4 catalysts in 80/20, 50/50 and 20/80 mass ratios were used during the test, artificial sunlight and natural solar radiation were tested at laboratory and pilot plant scale respectively. Besides, the kinetic reactions were evaluated according to the Langmuir-Hinshelwood model, the apparent velocity constants (kapp) were obtained for the TiO2/Fe3O4 catalysts. In the laboratory test, the TiO2/Fe3O4 catalyst (80/20) had a performance for 93.04% of discoloration, kapp = 0.0238 min-1, while for TiO2/Fe3O4 (50/50, 20/80) had an 83.46%, 65.00% for discoloration of MB and the kapp values were 0.0154 min-1 and 0.0098 min-1, respectively. In the solar test at pilot scale, the percentages of discoloration of 24.32%, and 57.78%, with kapp values of 0.00037 min-1, 0.00121 min-1 respectively were obtained for TiO2/Fe3O4 (80/20), a MB solution of 30 ppm, a load of 0.1 g/L and 0.3 g/L of the catalyst respectively. © 2020 The Author(s).Measurement of background radiations (BRs) as the sources of cancer risk, is important. The aim of this study was to measure the BR, as well as its cancer risk and mortalities in Kohgiluyeh and Boyer-Ahmad province (KBAp). Indoors and outdoors BRs were measured in eight cities utilizing a Geiger-Muller detector. Five main locations (north, east, west, south, and center) were chosen for measuring outdoor and indoor BRs in each city of KBAp. The BEIR VII-Phase 2 model was used to calculate the BRs induced cancer risks and mortalities of various cancer types at different ages. The average dose rates of outdoor and indoor were 136.9 ± 12.5 and 149.3 ± 19.8 nSv.h-1, respectively. The average annual effective doses (AEDs) for adults, children, and infants were 0.17, 0.19, and 0.22 mSv.y-1 due to the outdoor, and 0.73, 0.84, and 0.94 mSv.y-1 resulting from the indoor exposure, respectively. The average lifetime risk for one year BRs induced cancers was 164.8 ± 15.7 and 307.1 ± 32.3 (in 100,000 people) for new-borns male and female, in that order. This risk decreased with age and reached 11.2 ± 1.6 and 13.8 ± 1.6 (in 100,000 people) for men and women at the age of 80, respectively. The average lifetime risk of mortality due to cancers induced by annual BRs was 70.7 ± 8.3 and 113.8 ± 10.6 (incidence probability in 100,000 people) for new-borns male and female respectively. This risk decreased with age and reached 9.8 ± 1.3 and 12.2 ± 1.3 (in 100,000 people) for men and women at the age of 80 years, respectively. https://www.selleckchem.com/products/r16.html © 2020 The Author(s).This research was conducted to determine trends in the career interests of high school students in Surabaya, East Java, Indonesia. The sample size was 981 consisting of 488 men and 493 women. The instrument used was a career interest scale that was compiled based on Holland's theory with six RIASEC domains (Realistic, Investigative, Artistic, Social, Enterprising, and Conventional). The study design uses non-experimental, data collection through questionnaires given directly. Data were analyzed descriptively without using an explicit theoretical model. The career fields that are in high demand by high school students are the conventional fields that reach 42.30%, while the less desirable areas are the investigative fields which are only 3.98%. There are differences in career interests between men and women. Men prefer more realistic, artistic and enterprising fields, while women prefer social and conventional fields. © 2020 The Author(s).Gellan gum incorporating titanium dioxide nanoparticles biofilm was synthesized and characterized using UV, FTIR and XRD to study their physical and chemical properties. The mechanical properties were measured using universal mechanical testing. Meanwhile, the biological properties were investigated towards for antibacterial and cell proliferation. This comprehensive data are relevant with the research article entitled "Gellan gum incorporating titanium dioxide nanoparticles biofilm as wound dressing Physicochemical, mechanical, antibacterial properties and wound healing studies" [1]. © 2020 The Author(s).This article makes available a dataset that was used for the development of an automatic recognition system of peripheral blood cell images using convolutional neural networks [1]. The dataset contains a total of 17,092 images of individual normal cells, which were acquired using the analyzer CellaVision DM96 in the Core Laboratory at the Hospital Clinic of Barcelona. The dataset is organized in the following eight groups neutrophils, eosinophils, basophils, lymphocytes, monocytes, immature granulocytes (promyelocytes, myelocytes, and metamyelocytes), erythroblasts and platelets or thrombocytes. The size of the images is 360 × 363 pixels, in format jpg, and they were annotated by expert clinical pathologists. The images were captured from individuals without infection, hematologic or oncologic disease and free of any pharmacologic treatment at the moment of blood collection. This high-quality labelled dataset may be used to train and test machine learning and deep learning models to recognize different types of normal peripheral blood cells.

The treatment of Graves' hyperthyroidism (GD) complicated with malignancy is challenging, as anti-thyroid thionamide drugs (ATDs) and anti-cancer chemotherapy are both associated with a risk of neutropenia. Treatment with conventional ATDs, radioactive iodine (RAI) or potassium iodide (KI) was attempted in 8 patients with malignancy (34-80 years of age; 2 males and 6 females) in whom GD had been fortuitously diagnosed during a detailed systematic examination. Three patients requiring surgery were initially treated conventionally with methylmercaptoimidazole (MMI), MMI and KI or RAI (group A; one patient each). The patients became euthyroid on days 17-31 and underwent surgery on days 25-47. RAI therapy was administered to one patient after surgery. The patients were then treated with KI during chemotherapy. https://www.selleckchem.com/products/l-arginine-l-glutamate.html Five other patients who did not require surgery were initially treated with 100 mg KI monotherapy (group B). The serum free T4 level declined immediately in all of these patients, and they became euthyroid on days 7-18, remaining almost entirely euthyroid for more than 120 days. Anti-cancer chemotherapy was successfully completed for three of the patients while taking KI, despite the patients experiencing repeated episodes of anti-cancer chemotherapy-induced neutropenia. Our present findings suggest that, in patients with GD and malignancy, MMI + KI or RAI may be required if immediate surgery is scheduled, but KI monotherapy may be worth trying, if anti-cancer chemotherapy is scheduled, thus avoiding the possibility of thionamide-induced neutropenia.Vertebral fracture is the most common type of osteoporotic fracture. However, the prevalence of osteoporosis and osteoporotic vertebral fractures were not explored previously in the United Arab Emirates (UAE). This study aims to describe for the first time the demographic and morphological characteristics of patients with fragility vertebral fractures in the UAE through a retrospective review of the medical records of patients with low-trauma vertebral fractures who visited two tertiary centers during 2011-2016. The sex, age at the time of fracture, nationality, body mass index (BMI), and anatomical fracture location were recorded for each patient. Overall, 143 subjects were diagnosed with low-trauma vertebral fractures in the Emirate of Abu Dhabi during 2011-2016. Of these, 98 were women (68.5%) and 45 were men (31.5%). The overall mean patient age at diagnosis was 62.5 years, and almost half were younger than 65 years. Approximately 60% of the patients were UAE nationals. Fifty-one patients (36.7%) were obese (mean BMI 35.3 kg/m2), and women with vertebral fractures had a significantly higher mean BMI compared with men (p = 0.041). Nearly 40% of men had a normal BMI, compared with 20% of women. Most fractures were compression fractures (77.6%) in the thoracolumbar transition region. In conclusion, patients with fragility vertebral fractures were predominantly female and tended to be overweight or obese, although male patients tended to have a lower BMI than female patients.BACKGROUND The Harmonization By Doing (HBD) program was established in 2003 as a partnership among stakeholders of academia, industry and regulatory agencies in Japan and the United States, with a primary focus on streamlining processes of global medical device development for cardiovascular medical devices. While HBD has traditionally focused on development of devices intended to treat conditions prevalent in adults, in 2016, HBD established the "HBD-for-Children" program, which focuses on the development of pediatric devices as the development of medical devices for pediatric use lags behind that of medical devices for adults in both countries.Methods and ResultsActivities of the program have included (1) conducting a survey with industry to better understand the challenges that constrain the development of pediatric medical devices; (2) categorizing pediatric medical devices into five categories based on global availability and exploring concrete solutions for the early application and regulatory approval in both geographies; and (3) facilitating global clinical trials of pediatric medical devices in both countries. CONCLUSIONS The establishment of the HBD-for-Children program is significant because it represents a global initiative for the introduction of pediatric medical devices for patients in a timely manner. Through the program, academia, industry and regulatory agencies can work together to facilitate innovative pediatric device development from a multi-stakeholder perspective. This activity could also encourage industry partners to pursue the development of pediatric medical devices.BACKGROUND Thromboembolic complications such as ischemic stroke or peripheral arterial thromboembolism are known complications in hypertrophic cardiomyopathy (HCM). We sought to assess the clinical and cardiovascular magnetic resonance (CMR) characteristics of patients with HCM suffering from thromboembolic events and analyzed the predictors of these unfavorable outcomes.Methods and ResultsThe 115 HCM patients underwent late gadolinium enhanced (LGE) CMR and were included in the study. Follow-up was 5.6±3.6 years. The primary endpoint was the occurrence of thromboembolic events (ischemic stroke or peripheral arterial thromboembolism). It occurred in 17 (14.8%) patients (event group, EG), of whom 64.7% (11) were men. During follow-up, 10 (8.7%) patients died. Patients in the EG showed more comorbidities, such as heart failure (EG 41.2% vs. NEG (non-event group) 14.3%, P14.4%) is an independent predictor for thromboembolic complications in patients with HCM and might therefore be considered as an important risk marker. The risk for thromboembolic events is significantly elevated if accompanied by AF.The goal of this study was to review relevant randomized controlled trials in order to determine the clinical efficacy of levothyroxine in the treatment of overt or subclinical hypothyroidism. Using appropriate keywords, we identified relevant studies using PubMed, the Cochrane library, and Embase. Key pertinent sources in the literature were also reviewed, and all articles published through December 2019 were considered for inclusion. For each study, we assessed odds ratios (ORs), mean difference (MD), and 95% confidence interval (95%CI) to assess and synthesize outcomes. We included 25 studies with totally 1,735 patients in the meta-analysis. In the patients with hypothyroidism, compared with L-T4, L-T4 plus L-T3 significantly decreased TSH levels and increased FT3 levels. Compared with placebo, L-T4 significantly increased FT4 levels and decreased TSH levels. In patients with subclinical hypothyroidism, compared with placebo, L-T4 significantly decreased SBP, TSH, T3 and TC and increased FT3 and FT4.

progression compared with patients with HbA1c level below 6.5% (HR=2.838, 95%CI 1.505-5.349, P=0.001). Compared with non-diabetic patients, diabetic patients with HbA1c below 6.5% also had lower risk of lesion progression (HR=0.469, 95%CI 0.252-0.872, P=0.012). ST-segment elevated myocardial infarction was an independent predictor for revascularization of non-target lesions in diabetic patients. Conclusion Type 2 diabetes mellitus is not an independent predictor for progression and revascularization of coronary non-target lesions in patients with coronary heart disease. However, elevated HbA1c level is a risk factor for progression of non-target lesion in patients with type 2 diabetes mellitus.Objective To compare left ventricular myocardial mechanics detected by cardiac magnetic resonance tissue tracking(CMR-TT) between patients with constrictive pericarditis(CP) and restrictive cardiomyopathy(RCM),and see if those can be used to differentiate CP from RCM patients. Methods A total of 23 patients with CP, 20 patients with RCM, who hospitalized in Beijing Anzhen Hospital from January 2014 to April 2019 were included in this study and 25 healthy subjects served as control group, all subjects underwent cardiac magnetic resonance examination. Myocardial mechanics were evaluated by 2-dimensional(2D) and 3-dimensional(3D) CMR-TT in terms of global longitudinal strain(GLS), circumferential strain(GCS), radial strain(GRS) and the lateral wall strain to septal wall strain ratio(lateral/septal ratio) of basal, mid-cavity and apical. The diagnostic area under the receiver operating characteristic curve (ROC) was evaluated for differentiating CP from RCM. Results Age, sex and heart rate were similar between CP and RCM patients(all P>0.05). 2D-GLS, 3D-GLS, GCS and GRS in CP and RCM groups were significantly lower than those in normal control group(all P0.05). Compared with RCM, the circumferential and radial lateral/septal ratios of the basal were significantly lower in CP group than in RCM group(both P less then 0.05), AUC=0.737(sensitivity 70%, specificity 83%) and 0.737 (sensitivity 60%, specificity 87%), respectively. The left ventricular myocardial mechanics strain curve of the CP,RCM and normal control were different. The CP patients presented as " rapidly down-a platform" form, the RCM presented as "slowly down" form, and normal control presented as "rapidly down" form. Conclusion Evaluating the differences in the diastolic process of left ventricular myocardium and left ventricular myocardial mechanics strain curve is helpful to differentiate CP from RCM patients.Objective To investigate the association between smoking and the severity of coronary lesions among young and middle-aged female patients with acute coronary syndrome (ACS). Methods Data of this study were derived from the Improving Care for Cardiovascular Disease in China (CCC)-ACS project, a collaborative study of the Chinese Society of Cardiology and the American Heart Association. Since 2014, the CCC-ACS project consecutively enrolled inpatients with ACS, systematically collected their clinical data and evaluated medical quality of these patients from 158 tertiary hospitals and 82 secondary hospitals across China. This study enrolled female patients less than 60 years old with initial ACS, who received coronary angiography in CCC-ACS project. https://www.selleckchem.com/products/plicamycin.html Patients were divided into two groups according to smoking status. A multivariate logistic regression analysis was used to analyze the association between smoking and the severity of coronary lesions among young and middle-aged female patients with ACS. Results A tot elevated low-density lipoprotein cholesterol, lower high-density lipoprotein cholesterol, elevated triglyceride, renal insufficiency, family history of coronary heart disease and types of ACS, smokers faced a higher risk of coronary multi-vessel lesions, coronary multi-vessel severe lesions and coronary severe lesions with the odds ratios and 95% confidence interval of 1.41 (1.11-1.79), 1.40 (1.10-1.78) and 1.78 (1.11-2.87), compared with non-smokers. Conclusions Smoking is significantly associated with an increased risk of extensive and severe coronary lesions among young and middle-aged female patients with ACS. This study provides crucial evidence for further understanding the harms of smoking and the need to strengthen the tobacco control education and smoking cessation guidance for young and middle-aged women.Objective To investigate the influencing factors of in-stent restenosis (ISR) following successful stent implantation in patients with ablation-associated severe pulmonary vein stenosis (PVS) who undergo atrial fibrillation ablation. Methods Data of patients who underwent pulmonary vein angiography to confirm PVS after radiofrequency ablation for atrial fibrillation (AF) and received pulmonary vein stenting at Shanghai Chest Hospital from March 2010 to December 2017 were retrospectively analysed. All patients were followed up for a long period of time (pulmonary vein contract-enhanced CT within 6 to 12 months after operation was performed, and pulmonary angiography was performed if CT indicated stenosis>50%). The incidence of ISR was recorded. According to angiography, the patients were divided into ISR group and non-ISR group. The clinical and intraoperative imaging characteristics and interventional data were compared between the two groups. Logistic regression was used to analyse the influencing factors ofdistal vessel, stent diameter and post procedural minimal luminal diameter are the protective factors of ISR.Objective To compare clinical efficacy of interventional treatment with graft vessel and native coronary artery for patients with late saphenous vein grafts disease(SVGD) after coronary artery bypass grafting (CABG). Methods A total of 1 608 patients underwent CABG in Tianjin Chest from March 2014 to December 2017 were screened. During the follow-up period, 165 hospitalized patients with recurrence of angina pectoris within one year after CABG, who had at least one narrow vein graft(≥50%) confirmed by the coronary angiography were enrolled. According to the results of angiography and surgeon's clinical experiences, the patients received interventional treatment to vein grafts(grafts group, n=53) or native coronary vessels(native group, n=112). The operation success rate, mortality and incidence of serious complications after interventional treatment in two groups at the time of hospitalization were compared.And the incidence of major adverse cardiovascular events(MACE) in two groups at one year after discharge were also compared.

Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants. Conclusion Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.In the problem where there is not enough data to use Deep Learning, Bag-of-Visual-Words (BoVW) is still a good alternative for image classification. In BoVW model, many pooling methods are proposed to incorporate the spatial information of local feature into the image representation vector, but none of the methods devote to making each visual word have its own pooling regions. The practice of designing the same pooling regions for all the words restrains the discriminability of image representation, since the spatial distributions of the local features indexed by different visual words are not same. In this paper, we propose to make each visual word have its own pooling regions, and raise a simple yet effective method for learning pooling region. Concretely, a kind of small window named observation window is used to obtain its responses to each word over the whole image region. The pooling regions of each word are organized by a kind of tree structure, in which each node indicates a pooling region. For each word, its pooling regions are learned by constructing a tree with its labelled coordinate data. The labelled coordinate data consist of the coordinates of responses and image class labels. The effectiveness of our method is validated by observing if there is an obvious classification accuracy improvement after applying our method. Our experimental results on four small datasets (i.e., Scene-15, Caltech-101, Caltech-256 and Corel-10) show that, the classification accuracy is improved by about 1% to 2.5%. We experimentally demonstrate that the practice of making each word have its own pooling regions is beneficial to image classification task, which is the significance of our work.Introduction To prevent the 2.6 million newborn deaths occurring worldwide every year, health system improvements and changes in care-taker behaviour are necessary. Mothers are commonly assumed to be of particular importance in care-seeking for ill babies; however, few studies have investigated their participation in these processes. This study explores mothers' roles in decision making and strategies in care-seeking for newborns falling ill in Ethiopia. Methods A qualitative study was conducted in Butajira, Ethiopia. Data were collected during the autumn of 2015 and comprised 41 interviews and seven focus group discussions. Participants included primary care-takers who had experienced recent newborn illness or death, health care workers and community members. Data were analysed using thematic analysis. Results Choices about whether, where and how to seek care for ill newborns were made through cooperation and negotiation among household members. Mothers were considered the ones that initially identified or rcluding the head of households and extended family.Although identified to be at a higher risk of relapse, no consensus exists on the treatment of breast cancer (BC) patients with no pathological complete response after neoadjuvant chemotherapy (NAC). The benefit of adjuvant chemotherapy (ADJ) in this context has scarcely been studied. We evaluated the benefit of administrating adjuvant chemotherapy in a real life cohort of BC patients with invasive residual disease after NAC. 1199 female BC patients with T1-3NxM0 invasive tumors receiving NAC at Institut Curie from 2002 to 2012 were included in the analysis. 1061 had been treated by NAC only, whereas 138 had received additional adjuvant chemotherapy after NAC (FUN protocol 5-FU-Vinorelbine). We compared disease-free survival (DFS) and overall survival (OS) rates between patients having received NAC only and patients having received NAC+ADJ. To ensure comparability of our populations, we used a propensity score (which defines the probability of treatment assignment conditional on observed baseline covariates) and matched each patient having received NAC+ADJ (n = 138) with a patient having received NAC only that had a similar propensity score value. Before propensity score matching, DFS and OS rates were significantly lower in the NAC+ADJ group compared to NAC only, after 3 years, 5 years and 10 years follow-up (p less then 0.01). After one-to-one PS matching, the two groups were comparable (n = 276 patients; 138 patients in each group). No significant difference was found regarding DFS (p = 0.87) or OS (p = 0.59) rates, neither in global population, nor by pathological subtype. Although our study did not show a benefit of administrating ADJ with FUN protocol (5-Florouracil- Vinorelbine) to BC patients with residual disease after NAC, further studies are warranted to determine the impact of other adjuvant regimens. Thereby, patients with little chance of responding to particular regimens could avoid the toxicity of futile therapy, and be study participants in evaluations of novel treatment strategies.Background Studies comparing prevalence of alcohol use disorder (AUD) using DSM-IV and DSM-5 diagnostic criteria in college students are limited. This study examines changes in AUD prevalence estimates using DSM-IV versus DSM-5 and characterizes the profile of DSM-5 "diagnostic orphans." Methods and findings A college student sample (n = 1,155; mean age 21 ±1.97) selected conveniently from six large private and public universities in Greater Beirut, Lebanon completed an anonymous survey in May 2016. https://www.selleckchem.com/products/incb28060.html The study response rate was 83.1%. Data on DSM-IV and DSM-5 AUD criteria were gathered from 582 past-year drinkers, of which 377 (65%) were screened to have DSM-IV abuse/dependence, and 203 (35%) to have any DSM-5 AUD (58% mild, 21% moderate, and 21% severe). Overall percent agreement between measures was 68% (kappa = 0.41). One hundred and ninety-one students met one DSM-5 AUD criterion only (i.e. "diagnostic orphans," herein DOs), of which the majority (82%) endorsed "hazardous use." Compared to past-year drinkers with zero-endorsed DSM-5 criteria, DOs were more likely to be aged 21 or above [OR = 1.

Objectives. To assess if historical redlining, the US government's 1930s racially discriminatory grading of neighborhoods' mortgage credit-worthiness, implemented via the federally sponsored Home Owners' Loan Corporation (HOLC) color-coded maps, is associated with contemporary risk of preterm birth ( less then 37 weeks gestation).Methods. We analyzed 2013-2017 birth certificate data for all singleton births in New York City (n = 528 096) linked by maternal residence at time of birth to (1) HOLC grade and (2) current census tract social characteristics.Results. The proportion of preterm births ranged from 5.0% in grade A ("best"-green) to 7.3% in grade D ("hazardous"-red). The odds ratio for HOLC grade D versus A equaled 1.6 and remained significant (1.2; P less then .05) in multilevel models adjusted for maternal sociodemographic characteristics and current census tract poverty, but was 1.07 (95% confidence interval = 0.92, 1.20) after adjustment for current census tract racialized economic segregation.Conclusions. Historical redlining may be a structural determinant of present-day risk of preterm birth.Public Health Implications. Policies for fair housing, economic development, and health equity should consider historical redlining's impacts on present-day residential segregation and health outcomes.Objectives. To examine abortion utilization in Ohio from 2010 to 2018, a period when more than 15 abortion-related laws became effective.Methods. We evaluated changes in abortion rates and ratios examining gestation, geographic distribution, and abortion method in Ohio from 2010 to 2018. We used data from Ohio's Office of Vital Statistics, the Centers for Disease Control and Prevention's Abortion Surveillance Reports, the American Community Survey, and Ohio's Public Health Data Warehouse.Results. During 2010 through 2018, abortion rates declined similarly in Ohio, the Midwest, and the United States. In Ohio, the proportion of early first trimester abortions decreased; the proportion of abortions increased in nearly every later gestation category. Abortion ratios decreased sharply in most rural counties. When clinics closed, abortion ratios dropped in counties in which clinics were located and in surrounding counties.Conclusions. More Ohioans had abortions later in the first trimester, compared with national patterns, suggesting delays to care. Steeper decreases in abortion ratios in rural versus urban counties suggest geographic inequity in abortion access.Public Health Implications. Policies restricting abortion access in Ohio co-occur with delays to care and increasing geographic inequities. Restrictive policies do not improve reproductive health. (Am J Public Health. Published online ahead of print May 21, 2020 e1-e7. doi10.2105/AJPH.2020.305706).Objectives. To understand how the elimination of nonmedical vaccine exemptions through California Senate Bill 277 (SB277) may have resulted in increased spatial clustering of medical exemptions.Methods. We used spatial scan statistics and negative binomial regression models to examine spatial clustering in medical vaccine exemptions in California kindergartens from 2015 to 2018.Results. Spatial clustering of medical exemptions across schools emerged following SB277. https://www.selleckchem.com/products/pf-06952229.html Clusters were located in similar geographic areas to previous clusters of nonmedical vaccine exemptions, suggesting a spatial association between high nonmedical exemption prevalence and increasing rates of medical exemptions. Regression results confirmed this positive association at the local level. The sociodemographic characteristics of the neighborhoods in which schools were located explained some, but not all, of the positive spatial associations between exemptions before and after SB277.Conclusions. Elimination of nonmedical vaccine exemptions via SB277 may have prompted some parents to instead seek medical exemptions to required school vaccines. The spatial association of these 2 types of exemptions has implications for maintaining pockets of low vaccine compliance and increased disease transmission.This study was concerned with a culture-sensitive revision of the Turkish version of the Childhood Trauma Questionnaire (CTQ-28) and expansion of the instrument through integration of a dimension assessing overprotection - overcontrol (OP-OC). Participants (n = 783) were 37 dissociative and 78 non-dissociative and non-psychotic psychiatric outpatients, and 668 non-clinical people. They completed the revised and expanded version of the CTQ, Dissociative Experiences Scale, Beck Depression Scale, and Relationship Scales Questionnaire. A test-retest assessment was conducted on 25 non-clinical individuals. Among twenty-one alternative and the twenty-five original statements, the items of subsections were selected by correlations between item and item deleted total scores for each subset of original and alternative statements. The 33-item final version (CTQ-33) included five statements for each subsection including OP-OC and three denial items. The principal component analysis on items of the CTQ-33 with a varimax rotation yielded six factors including OP-OC. The inner consistency and the test-retest reliability were good. OP-OC correlated particularly with emotional abuse and neglect, and other types of trauma. There were significant correlations between CTQ-33 and depression, dissociation, and fearful attachment scores. The CTQ-33 differentiated psychiatric from non-clinical groups. The Turkish CTQ-33 is a reliable and valid instrument. OP-OC by caregivers may be as traumatic as other types of childhood adversities. Cross-cultural research would illuminate the significance of OP-OC beyond Turkish culture. The possibility of intergenerational transmission of trauma through OP-OC by fearful parents in and after times of cultural upheaval and political oppression should be considered for future research.Objectives The purpose of this study is to ascertain the etiology of bilateral sensorineural hearing loss (SNHL) in children aged ≤ 18 years living in Shandong province. Method Data were taken from a cross-sectional study, which was conducted between 2015 and 2017. The study included children aged ≤ 18 years, recruited from special schools for children with hearing loss and from hearing rehabilitation centers in Shandong province of China. Children were screened for bilateral SNHL through audiological testing. Clinical examination, genetic testing, and structured interviews were conducted for those children who were identified as having hearing loss to identify the potential cause. Results The etiology of bilateral SNHL in our sample was genetic in 874 (39.3%), acquired in 650 (29.3%), and unknown in 697 (31.4%) children. Among children with acquired SNHL, the cause was maternal viral infection in 75 (11.5%); perinatal factors in 238 (36.6%); meningitis, measles, and mumps in 146 (22.5%); and ototoxic exposure in 117 (18%) children.

Pyrolysis of malt bagasse was carried out to obtain simultaneously a mesoporous biochar and an oil fraction rich in palmitic acid. The best result for biochar production was at 500 °C with holding time of 10 min. The yields of biochar and pyrolytic oil in this condition were, 29.7 and 33.9 wt%, respectively. The pyrolysis temperature and holding time influenced the yields of the products. An increase in pyrolysis temperature (from 500 to 700 °C) and holding time (from 10 to 50 min) caused a decrease in biochar yield, a reduction in the volatile matter content and an increase in the amount of ash. Additionally, in the range studied in this work, the increase of the pyrolysis temperature caused a decrease in the specific surface area and total pore volume of the biochar. Meanwhile, the biochar presented interesting functional groups and a mesoporous character, which can be a precursor to obtain adsorbents, or even, be used as adsorbent. The pyrolytic oil was composed of oxygenated aromatic compounds, the main fraction being palmitic acid (27.3%), which can be used in a number of applications, including biodiesel production. This work demonstrated that an available and problematic waste, malt bagasse, can be converted simultaneously into a mesoporous biochar and, into a pyrolytic oil rich in palmitic acid. Biochar and pyrolytic oil, in turn, are products of great value and can be applied in several fields.An efficient process is proposed for recovery of waste LiMn2O4 cathode material, which is one of the most commonly used cathode materials in LIBs. This report constitutes the precipitation thermodynamic analysis and separation experiments based on the water-leaching solutions during the processes of low-temperature calcination with (NH4)2SO4 and water-leaching. Precipitation thermodynamic analysis is undertaken to investigate the effects of initial concentration of the target solution, [N]T1, excess precipitant, and addition of (NH4)2SO4 on the manganese precipitation in the Mn2+-Li+-SO42--NH3-NH4+-CO32--H2O system. Moreover, the effects of initial concentration of the target solution, [N]T2, and excess precipitant on the lithium precipitation in the Li+-SO42--NH3-NH4+-CO32--H2O system are investigated. All these factors clearly influence the manganese and lithium precipitation, particularly the [N]T and the presence of excess precipitant in the system. The precipitation experimental results demonstrate that the optimal conditions are a precipitation temperature of 35 °C; an excess coefficient of the precipitant of 2.4; the use of NHC-3 to precipitate the ML-3 solution; a maximum precipitation percentage of manganese of 99.96%; and an absence of Li2CO3 precipitation. The double-sulfate salts (Li(NH4)SO4 & (NH4)2SO4) evaporated and crystallised from the Li+/NH4+ solution are mixed with the waste LiMn2O4 cathode material for calcination and water leaching, for which the efficiencies of Li and Mn are 100% and 96.89%, respectively. The double-sulfate salts are calcined at 550 °C for 45 min to obtain the Li2SO4 product. Finally, the complete recovery and separation of Mn and Li in the waste LiMn2O4 cathode material are achieved.Due to no specific symptoms and lack of early diagnosis for ovarian cancer, most diagnosed patients are often in the terminal stage resulting that tumor tissue is unable to be resected completely by operation. So postoperative chemotherapy has become an important and indispensable treatment procedure for them. Up to date, it remains a challenge to treat ovarian cancer by an effective chemotherapy strategy. Recently, the strategy of ADDC has been regarded as a highly effective chemotherapy strategy to treat various cancers without any drug carriers. Here a novel ADDC is synthesized by linking a water-soluble antitumor drug floxuridine (Fud) and a water-insoluble antitumor drug chlorambucil (Cb) through the esterification. Then the Fud-Cb conjugate can form stable nanodrugs in water with an average size around 103.0 nm through molecular self-assembly. After internalization of cells, the ester bonds in nanodrugs can be degraded to release free Fud and Cb at a fixed ratio under the intracellular acid conditions, which exhibits the high synergistic effect on ovarian cancer cells. The cytotoxicity test results show that Fud-Cb nanodrugs can efficiently inhibit the growth of ovarian cancer cells. The apoptosis data exhibit that the cell necrotic and apoptotic rate treated with Fud-Cb nanodrugs is about 73.7 % and 18.76 % within 24 h. These results suggest that Fud-Cb nanodrugs based on ADDC strategy can effectively enhance synergistic anticancer efficacy to ovarian cancer.In natural and engineered settings, bacteria predominantly thrive in biofilms, which are complex microbial communities embedded in a self-produced extracellular polymeric substances (EPSs) matrix. Pellicles are complex macroscopic biofilms floating at air-water interface. Though pellicle formation has been studied in detail in Bacillus subtilis, a soil bacterium, it is not reported in aquatic bacteria, which may use pellicle-growth as survival-strategy. This study shows that Bacillus haynesii isolated from a marine environment forms robust pellicle biofilms at air-water interface. B. haynesii pellicles showed complex architecture, involving dense cell-aggregates with interconnecting thread-like structures in an extracellular matrix. In situ staining by Alcian blue, Concanavalin A and ThioflavinT (ThT), respectively, localized acidic polymers, glycoconjugates and amyloid-like fibers in the pellicle. The pellicle was rigid and not disrupted by common EPS extraction protocols. Hence, a set of reagents and conditions were evaluated for solubilizing the EPS and pellicle. https://www.selleckchem.com/products/avelumab.html Acetic acid was able to effectively solubilize the structural EPS and pellicle structure. Acid soluble structural EPS contained chemical signatures for both proteins and carbohydrates, as revealed by elemental analysis, Fourier Transform Infrared Spectroscopy and Raman Spectroscopy. Ex situ staining of acid soluble EPS by ThT showed recovery of amyloid-forming proteins from pellicle. Results show that structural stability of the pellicle is mainly conferred by amyloid-like fibers of the EPS matrix. The robust pellicle-growth reported here may represent a survival-strategy in the aquatic bacterium. The findings reported here can support future research on biofilm structure, EPS matrix and its formation, which are critical for understanding how microbes thrive in natural and engineered settings.

3% and 76.5% in samples diagnosed as suspicious for malignancy (n = 17) and in 57.2% of samples diagnosed with atypia (n = 14). The Odds Ratio for breast malignancy was 4.545 in patients with RASSF1A hypermethylation and 9.167 in patients with RAR-β2 hypermethylation underlying their promoter's methylation positive correlation with breast malignancy. Conclusion To optimize the sensitivity and specificity of this epigenetic setting, more TSGs related to BC should be gradually imported in our evaluated methylation panel and be validated in a larger study sample with the aim that the obtained epigenetic profiles will provide clinicians with valuable tools for management of BC patients in Greece.Background Motor phenotypes in Huntington's disease vary manifold. Phenotype classification is essential to adapt treatment. The aim of this study was to classify a dystonic subtype closer. Methods A total of 7,512 manifest ENROLL-HD participants were subdivided into mainly choreatic (N = 606), dystonic (N = 402), and hypokinetic-rigid (N = 369) subjects. Cognitive (verbal fluency, symbol digit, stroop color, trail making, Mini-Mental State Examination), functional (total functional capacity, Independence Scale), and psychiatric (problem behaviors assessment, Hospital Anxiety and Depression Scale) performance was evaluated at baseline visit. Results Symptoms onset for dystonic were similar to hypokinetic-rigid, but earlier compared to choreatic subjects (p less then .001). Cognition was better in both groups compared to hypokinetic rigid (all p less then .001). Functionality differed between all groups (all p less then .001). Differences remained (all p less then .001) after controlling for CAP score, CAG, age, disease duration, and education. Conclusions Motor subtypes differ in functional and cognitive capacities but less in psychiatric. We identified better cognitive and functional capacities and similar onsets in predominant dystonic compared to hypokinetic-rigid patients.Background Minimal residual disease (MRD) assessment of hematopoietic neoplasia below 10-4 requires more leukocytes than is usually attainable by post-lysis preparation. However, not all laboratories are resourced for consensus Euroflow pre-lysis methodology. Our study aim was to validate a modified pre-lysis protocol against our standard post-lysis method for MRD detection of multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and B-non Hodgkin lymphoma (B-NHL), to meet demand for deeper MRD assessment by flow cytometry. Method Clinical samples for MRD assessment of MM, CLL, and B-NHL (50, 30, and 30 cases, respectively) were prepared in parallel by pre and post-lysis methods for the initial validation. Total leukocytes, MRD, and median fluorescence intensity of antigen expression were compared as measures of sensitivity and antigen stability. Lymphocyte and granulocyte composition were compared, assessing relative sample processing stability. Sensitivity of the pre-lysis assay was monitored post validation for a further 18 months. Results Pre-lysis achieved at least 10-4 sensitivity in 85% MM, 81% CLL, and 90% B-NHL samples versus 24%, 48%, and 26% by post-lysis, respectively, with stable antigen expression and leukocyte composition. Post validation over 18 months with technical expertise improving, pre-lysis permitted 10-5 MRD assessment in 69%, 86%, and 82% of the respective patient groups. https://www.selleckchem.com/products/az-33.html Conclusion This modified pre-lysis procedure provides a sensitive, robust, time efficient, and relatively cost-effective alternative for MRD testing by MFC at 10-5 , facilitating clinically meaningful deeper response assessment for MM, CLL, and B-NHL. This method adaptation may facilitate more widespread adoption of highly sensitive flow cytometry-based MRD assessment.Background The role of retrospective analysis has been evolved greatly in cancer research. We undertook this meta-analysis to evaluate the diagnostic value of Neural networks (NNs) in Fine needle aspiration cytological (FNAC) image of cancer. Methods We systematically retrieved 396 literatures on cytodiagnosis of NNs from Cochrane, PubMed, and EMBASE. After screening, only six studies were included in meta-analysis finally. Data was comprehensively analyzed by RevMan and meta-Disc software. Results A total of 1165 cases were extracted from six articles. Among them, 593 cases were in the abnormal/positive group and 572 cases in the normal/negative group. The pooled estimates for the NNs cytology were Area under ROC curve (AUC) 0.99, Sensitivity 0.85 (95% CI0.82-0.88), Specificity 0.96 (95% CI0.94-0.97), Positive Likelihood Ratio (LR)18.43 (95% CI6.83-49.74), Negative Likelihood Ratio (LR) 0.06 (95% CI0.001-0.58), and Diagnostic odds ratio (DOR) 343.21 (34.41-3422.77). Conclusions This meta-analysis confirms that NNs Automated Classification algorithm can facilitate to some extent the FNCA diagnosis of cancer.Introduction The antenatal diagnosis of sagittal craniosynostosis can be challenging, but there are several published papers describing a traumatic outcome to both the affected fetus and the mother during delivery of a scaphocephalic child. The antenatal imaging from affected children was collected along with the mother's obstetric history. The aim of this study was to identify antenatal ultrasound features that may assist the diagnosis of sagittal synostosis before birth, to enable appropriate delivery planning and avoid both maternal and fetal trauma during birth. Methods Antenatal ultrasound scans in both the second and third trimesters were traced for 36 children with sagittal synostosis. The initially diagnostic CT scans were also sourced. A delivery history was collected from the hospital case notes where available. Results The affected group showed a statistically significant reduction in cephalic index during the second half of pregnancy compared with the normal population which became slightly more brachycephalic (P = 0.001). Regression analysis showed an average reduction in cephalic index of 0.57 units per month. There was also a much higher rate of malpresentation and surgical deliveries in the affected group than the normal population. There was a relationship between sagittal craniosynostosis and breech presentation and an associated higher rate of surgical deliveries. Conclusion It is possible to detect sagittal synostosis in the third trimester of pregnancy which may assist with delivery planning.

86). Moreover, the deep learning system succeeded to stratify patients into high-risk and low-risk groups whose hospital-stay time have significant difference (p=0.013 and 0.014). Without human-assistance, the deep learning system automatically focused on abnormal areas that showed consistent characteristics with reported radiological findings.Deep learning provides a convenient tool for fast screening COVID-19 and finding potential high-risk patients, which may be helpful for medical resource optimisation and early prevention before patients show severe symptoms.Purpose HIV infection is an exclusion criterion in lung cancer trials. This multicenter phase II trial aimed to assess feasibility, efficacy and safety of first-line carboplatin plus pemetrexed (CaP) followed by pemetrexed (P) maintenance in people living with HIV (PLHIV) with advanced non-squamous non-small cell lung cancer (NS-NSCLC). https://www.selleckchem.com/products/SB-743921.html Methods Four cycles of CaP were followed by P-maintenance therapy in patients with Eastern Cooperative Oncology Group performance status (PS) ≤2. The primary objective was a disease control rate (DCR) ≥30% after 12 weeks. Results Of the 61 PLHIV enrolled 49 (80%) had a PS 0-1, 19 (31%) brain metastases. Median CD4 lymphocyte count was 418 cells·µL-1 (range 18-1230), median CD4 lymphocyte nadir 169.5 cells·µL-1 (1-822); 48 patients (80%) were virologically controlled. Four-cycle inductions were achieved by 38 patients (62%), and 31 (51%) started P maintenance [median of 4.1 cycles (range 1-19)]. The 12-week DCR was 50.8% (95%CI 38.3;63.4) and partial response rate 21.3%. Median PFS and OS were respectively 3.5 (95%CI 2.7;4.4) and 7.6 months (5.7;12.8). Patients with PS 0-1 had the longest median PFS (4.3 months, 95%CI 3.1;5.2) and OS (11.9 months, 95%CI 6.4;14.3). During induction, CaP doublet was well tolerated apart from grade 3-4 hematologic toxicities (neutropenia, 53.8%; thrombocytopenia, 35.0%; anemia, 30.0%). Two fatal treatment-related sepsis were reported. No opportunistic infections were experienced. Conclusion In PLHIV with advanced NS-NSCLC, first-line 4-cycle CaP induction followed by P maintenance was effective and reasonably well-tolerated. Further studies should evaluate combination strategies of CaP with immunotherapy in PLHIV.Current methods to replace damaged upper airway epithelium with exogenous cells are limited. Existing strategies use grafts that lack mucociliary function, leading to infection and the retention of secretions and keratin debris. Strategies that regenerate airway epithelium with mucociliary function are clearly desirable and would enable new treatments for complex airway disease. Here, we investigated the influence of the extracellular matrix on airway epithelial cell adherence, proliferation and mucociliary function in the context of bioengineered mucosal grafts. In vitro, primary human airway epithelial cells adhere most readily to collagen IV. Biological, biomimetic and synthetic scaffolds were compared in terms of their extracellular matrix protein content and airway epithelial cell adherence. Collagen IV and laminin were preserved on the surface of decellularised dermis and epithelial cell attachment to decellularised dermis was greater than to the biomimetic or synthetic alternatives tested. Blocking epithelial integrin α2 led to decreased adherence to collagen IV and to decellularised dermis scaffolds. At air-liquid interface, bronchial epithelial cells cultured on decellularised dermis scaffolds formed a differentiated respiratory mucosal layer with mucociliary function. Using in vivo chick chorioallantoic membrane and rabbit airway models, we showed short-term preservation of the differentiated cell layer following transplantation. Our results demonstrate the feasibility of generating human airway epithelial cell grafts on clinically applicable decellularised dermis scaffolds and identify matrix proteins and integrins important for this process. The long-term survivability of pre-differentiated epithelia and the relative merits of this approach against transplanting basal cells should be assessed further in pre-clinical airway transplantation models.Background The development of contractile muscle fatigue (CMF) affects training responses in patients with COPD. Downhill walking induces CMF with lower dyspnoea and fatigue than level walking. This study compared the effect of pulmonary rehabilitation (PR) comprising downhill walking training (DT) to PR comprising level walking (conventional training, CT) in patients with COPD. Methods In this randomised controlled trial, thirty five patients (62±8 years; FEV1 50±17%pred) were randomised to DT or CT. Exercise tolerance (6-minute walk test distance, 6MWD [primary outcome]), muscle function, symptoms, quality-of-life and physical activity levels were assessed before and after PR. Absolute training changes and the proportion of patients exceeding the 30 m 6MWD minimally important difference (MID) were compared between groups. Quadriceps muscle biopsies were collected after PR in a subset of patients to examine physiological responses to long-term eccentric training. Results No between-group differences were observed in absolute 6MWD improvement (mean 6MWD Δ77±46 m DT versus 56±47 m CT; p=0.45), however 94% of patients in DT exceeded the 6MWD MID compared to 65% in CT (p=0.03). Patients in DT tended to have larger improvements than CT in other outcomes. Muscle biopsy analyses did not differ between groups. Conclusion PR incorporating downhill walking confers similar magnitudes of effects to PR with conventional walking across clinical outcomes in patients with COPD, however offers a more reliable stimulus to maximise the achievement of clinically relevant gains in functional exercise tolerance in people with COPD.Background In clinical trials, the two anti-IL-5 monoclonal antibodies (mAbs, mepolizumab and reslizumab) that are approved to treat severe eosinophilic asthma, reduce exacerbations by approximately 50-60%. Objective To observe response to anti-IL-5 mAbs in real-life clinical setting, and to evaluate predictors of sub-optimal response. Methods In four Canadian academic centres, pre-defined clinical end-points in 250 carefully characterised moderate-to-severe asthmatics were collected prospectively to assess response to the two anti-IL-5 mAbs. Sub-optimal responses was determined based on failure to reduce maintenance corticosteroid (MCS) or asthma symptoms scores (ACQ) or exacerbations, in addition to persistence of sputum/blood eosinophils. Worsening in suboptimal responders were assessed based on reduced lung function by 25% or any increase in MCS/ACQ. A representative sub-set of 39 patients were evaluated for inflammatory mediators, autoantibodies and complement activation in sputum (by ELISA) and for immune-complex deposition by immunostaining formalin-fixed paraffin-embedded sputum plugs.