ResearchPad - development https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Predictors of change of health workers’ knowledge and skills after the Helping Mothers Survive Bleeding after Birth (HMS BAB) in-facility training in Tanzania]]> https://www.researchpad.co/article/elastic_article_15768 Our study aimed to assess the effect of Helping Mothers Survive Bleeding after Birth on knowledge and skills of health workers and whether such effect varies by health workers characteristics.MethodsNested in a cluster-randomised trial to assess the effect of the training on health outcomes, we assessed changes in knowledge and simulated skills in 61 facilities. The assessments were done i) before, ii) immediately-after training session and iii) at 10-month follow-up for subset of health-workers of implementation facilities as defined by the trial. We used a self-administered questionnaire and Objective Structures Clinical Examinations to assess three skill sets: Active Management of Third Stage of Labour, removal of retained placenta and management of severe postpartum haemorrhage. We computed summary statistics and used the paired t-test to assess change of knowledge and skills immediately post-training and at 10-month follow-up. Linear regression was done to assess association of scores and health worker characteristics.ResultsOf the 636 health workers included, 606 (96.7%) and 591 (91.4%) completed the knowledge and skills assessments, respectively. Majority of the participants (68%) were nurse-midwives. Knowledge scores increased by 15 percentage-points from 77.5% to 93% (95% CI 14.3, 16.3, p-value <0.000), and skills scores by 47 percentage-points (95% CI 46.5, 49.2, p-value <0.000) from 37.5% to 83%. There was a 4.0% decline of skills at 10-month follow-up. The decline was higher in auxiliary staff (-11.8%) and least in nurse-midwives (-2.1%) p-value <0.001. Health workers who assisted less than 5 deliveries in the last month, those who never attended postpartum haemorrhage in-service training and profession experience >8 years were associated with lower mean skill change immediately post-training.ConclusionOur study supports the potential of the Helping Mothers Survive Bleeding after Birth training to increase knowledge and skills of postpartum haemorrhage among all professional groups. Auxiliary staff benefited most from the training but also showed higher skill decline at 10-month. Our study highlights the importance to disaggregate knowledge and skills by health workers characteristics. ]]> <![CDATA[Naringenin mitigates autoimmune features in lupus-prone mice by modulation of T-cell subsets and cytokines profile]]> https://www.researchpad.co/article/elastic_article_15753 Naringenin is flavonoid mainly found in citrus fruits which has shown several biological properties. In this work, we evaluated the therapeutic potential of the flavonoid Naringenin. Five-month-old B6.MRL-Faslpr/J lupus-prone mice were administered daily orally with Naringenin for seven months. We showed that Naringenin treatment at 50 or 100 mg/kg inhibited the splenomegaly and decreased the levels of anti-nuclear and anti-dsDNA autoantibodies. Furthermore, a reduction in serum concentration of TNF-α, IFN-γ and IL-6 was observed in the mice provided with Naringenin. Interestingly, serum levels of IL-10 increased. Naringenin decreased the frequency and absolute numbers of splenic effector memory T cells. Additionally, in order to be able to evaluate whether Naringenin prevented kidney damage, twelve-week-old MRL/MpJ-Faslpr/J mice, an accelerated lupus model, were orally administered with Naringenin at 100 mg/kg for six weeks. Surprisingly, Naringenin treatment prevented kidney damage and reduced the development of fibrosis similar to cyclophosphamide group. Moreover, Naringenin treatment increased the percentage of regulatory T cells in this aggressive model of lupus. Together, these results suggest a potential ability of Naringenin to reduce the autoimmunity in lupus-prone mice by modulation of T-cell subsets and cytokines profile that mitigate the development of important lupus clinical manifestations.

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<![CDATA[Association between single nucleotide polymorphisms (SNPs) of IL1, IL12, IL28 and TLR4 and symptoms of congenital cytomegalovirus infection]]> https://www.researchpad.co/article/elastic_article_15749 Congenital cytomegalovirus (cCMV) infection is the most common intrauterine infection. A non-specific immune response is the first line of host defense mechanism against human cytomegalovirus (HCMV). There is limited data on associations between Single Nucleotide Polymorphisms (SNPs) in genes involving innate immunity and the risk and clinical manifestation of cCMV infection. The aim of the study was to investigate association between selected SNPs in genes encoding cytokines and cytokine receptors, and predisposition to cCMV infection including symptomatic course of disease and symptoms. A panel of eight SNPs: IL1B rs16944, IL12B rs3212227, IL28B rs12979860, CCL2 rs1024611, DC-SIGN rs735240, TLR2 rs5743708, TLR4 rs4986791, TLR9 rs352140 was analyzed in 233 infants (92 cCMV-infected and 141 healthy controls). Associations between genotyped SNPs and predisposition to cCMV infection and symptoms were analyzed. The association analysis was performed using SNPStats software. No statistically significant association was found between any genotyped SNPs and predisposition to cCMV infection and symptomatic course of disease. In relation to particular symptoms, polymorphism of IL12B rs3212227 was linked to decreased risk of prematurity (OR = 0.37;95%CI,0.14–0.98;p = 0.025), while polymorphism of IL1B rs16944 was linked to reduced risk of splenomegaly (OR = 0.36;95%CI,0.14–0.98; p = 0.034) in infants with cCMV infection. An increased risk of thrombocytopenia was associated with IL28B rs12979860 polymorphism (OR = 2.55;95%CI,1.03–6.32;p = 0.042), while hepatitis was associated with SNP of TLR4rs4986791 (OR = 7.80;95%CI,1.49–40,81; p = 0.024). This is the first study to demonstrate four new associations between SNPs in selected genes (IL1B, IL12B, IL28B, TLR4) and particular symptoms in cCMV disease. Further studies on the role of SNPs in the pathogenesis of cCMV infection and incorporation of selected SNPs in the clinical practice might be considered in the future.

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<![CDATA[Meta-analysis of the correlation between dietary copper supply and broiler performance]]> https://www.researchpad.co/article/elastic_article_15740 To conduct a meta-analysis assessing the correlation between dietary copper supply and broiler performanceMethodsStudies that were published prior to January 2019 and reported the dietary copper supply and broiler growth performance were identified using search functions in the Web of Science, Springer, Elsevier, Science Direct, and Taylor & Francis Online databases; the Journal of Dairy Research; and China National Knowledge Infrastructure (CNKI). We performed stratified analyses on the possible sources of bias, including differences in the study locations and years of publication. The publication bias was assessed with Egger’s test method.ResultsA total of 12 randomized controlled trial (RCT) studies were eligible for inclusion. The pooled WMDs of the ADG, ADFI and FCR were -0.166 (95% CI: -1.587 to 1.254), -0.844 (95% CI: -1.536 to -0.152) and -0.029 (95% CI: -0.057 to 0.000), respectively. In the Israeli and Indian studies, the ADG and ADFI data in the experimental group were higher than those in the control group; however, in America, a relatively high FCR value was found in the experimental group compared to that in the control group. The analysis of the study period showed that for the 1980s and 2010s, the ADG and ADFI of the experimental group were lower than those of the control group, while, in the 1990s and 2010s, the FCR of the experimental group were lower than those of the control group. The observed values were adjusted for study effects, and a model was used to obtain the copper supplementation under the optimal production performance. The results showed that the adjusted average daily gain (ADG), average daily feed intake (ADFI), and feed to gain ratio (FCR) presented a quadratic relationship with Cu supplementation (P<0.05). The maximum value of ADG (31.84 g/d) is reached when Cu is added at amount of 158 mg/kg, and the minimum value of FCR (1.53) is reached when Cu is added at amount of 217 mg/kg. No significant publication bias existed in the studies (Egger's test: P value were 0.81, 0.71 and 0.14).ConclusionFrom this study, it can be concluded that the traditional copper addition is no longer suitable for modern broiler breeding; the higher copper content may be beneficial for the production performance of broilers. ]]> <![CDATA[ToyArchitecture: Unsupervised learning of interpretable models of the environment]]> https://www.researchpad.co/article/elastic_article_15730 Research in Artificial Intelligence (AI) has focused mostly on two extremes: either on small improvements in narrow AI domains, or on universal theoretical frameworks which are often uncomputable, or lack practical implementations. In this paper we attempt to follow a big picture view while also providing a particular theory and its implementation to present a novel, purposely simple, and interpretable hierarchical architecture. This architecture incorporates the unsupervised learning of a model of the environment, learning the influence of one’s own actions, model-based reinforcement learning, hierarchical planning, and symbolic/sub-symbolic integration in general. The learned model is stored in the form of hierarchical representations which are increasingly more abstract, but can retain details when needed. We demonstrate the universality of the architecture by testing it on a series of diverse environments ranging from audio/visual compression to discrete and continuous action spaces, to learning disentangled representations.

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<![CDATA[The influenza replication blocking inhibitor LASAG does not sensitize human epithelial cells for bacterial infections]]> https://www.researchpad.co/article/elastic_article_14740 Severe influenza virus (IV) infections still represent a major challenge to public health. To combat IV infections, vaccines and antiviral compounds are available. However, vaccine efficacies vary with very limited to no protection against newly emerging zoonotic IV introductions. In addition, the development of resistant virus variants against currently available antivirals can be rapidly detected, in consequence demanding the design of novel antiviral strategies. Virus supportive cellular signaling cascades, such as the NF-κB pathway, have been identified to be promising antiviral targets against IV in in vitro and in vivo studies and clinical trials. While administration of NF-κB pathway inhibiting agents, such as LASAG results in decreased IV replication, it remained unclear whether blocking of NF-κB might sensitize cells to secondary bacterial infections, which often come along with viral infections. Thus, we examined IV and Staphylococcus aureus growth during LASAG treatment. Interestingly, our data reveal that the presence of LASAG during superinfection still leads to reduced IV titers. Furthermore, the inhibition of the NF-κB pathway resulted in decreased intracellular Staphylococcus aureus loads within epithelial cells, indicating a dependency on the pathway for bacterial uptake. Unfortunately, so far it is not entirely clear if this phenomenon might be a drawback in bacterial clearance during infection.

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<![CDATA[Cessation of breastfeeding in mothers of preterm infants—A mixed method study]]> https://www.researchpad.co/article/elastic_article_14739 Many women cease breastfeeding earlier than desired. This study examined the cessation of breastfeeding among mothers of preterm infants. Thus, the aim was to describe the cessation of breastfeeding in mothers of preterm infants up to 12 months after birth.MethodThis mixed methods study used a convergent design with both qualitative data, consisting of written comments, and quantitative data, on breastfeeding status and breastfeeding satisfaction. The data were collected from questionnaires sent to the mothers at three points during the first year after birth. In total, 270 mothers of preterm infants who breastfed at the time of discharge from the neonatal unit provided data for the study. The quantitative and qualitative data were analysed separately with statistical tests and hermeneutical analysis, respectively and then together according to the convergent mixed methods design.ResultsFour themes of the meanings of the cessation of breastfeeding were identified in the qualitative analysis: “Desire to regain the mother’s and the infant’s well-being”, “The mothers interpretation that the infants actively ceased breastfeeding”, “The mother’s body and/or the infants’ signals showing the way” and “The mother's own will and perceived external obstacles”. Mothers who did not breastfeed as long as they wanted were more likely to report less satisfaction with breastfeeding, a shorter breastfeeding period, and less activity when ceasing breastfeeding. In comparison, mothers who breastfed as long as they wanted were more satisfied with breastfeeding, breastfed for a longer period of time and were more active in decision making in breastfeeding cessation.ConclusionMaternal passivity or activity influenced the cessation of breastfeeding in mothers of preterm infants who breastfed at the time of discharge from the neonatal unit. Passive behaviour related to breastfeeding may result in early cessation of breastfeeding, and low breastfeeding satisfaction while active behaviour may increase breastfeeding length and satisfaction. ]]> <![CDATA[The influence of spouses and their driving roles in self-regulation: A qualitative exploration of driving reduction and cessation practices amongst married older adults]]> https://www.researchpad.co/article/elastic_article_14735 There is growing evidence to suggest the importance of self-regulatory practices amongst older adults to sustain mobility. However, the decision to self-regulate driving is a complex interplay between an individual’s preference and the influence of their social networks including spouse. To our best knowledge, the influence of an older adult’s spouse on their decisions during driving transition has not been explored.Materials and methodsThis qualitative descriptive study was conducted amongst married older adults aged 60 years and above. All interview responses were transcribed verbatim and examined using thematic approach and interpretative description method.ResultsA total of 11 married couples were interviewed. Three major themes emerged: [1] Our roles in driving; [2] Challenges to continue driving; and, [3] Our driving strategies to ensure continued driving. Older couples adopted driving strategies and regulated their driving patterns to ensure they continued to drive safely. Male partners often took the active driving role as the principal drivers, while the females adopted a more passive role, including being the passenger to accompany the principal drivers or becoming the co-driver to help in navigation. Other coping strategies include sharing the driving duties as well as using public transportation or mixed mode transportation.DiscussionOur findings suggest spouse play a significant role in their partners’ decision to self-regulate driving. This underscores a need to recognise the importance of interdependency amongst couples and its impact on their driving decisions and outcomes. ]]> <![CDATA[Influence of total western diet on docosahexaenoic acid suppression of silica-triggered lupus flaring in NZBWF1 mice]]> https://www.researchpad.co/article/elastic_article_14732 Lupus is a debilitating multi-organ autoimmune disease clinically typified by periods of flare and remission. Exposing lupus-prone female NZBWF1 mice to crystalline silica (cSiO2), a known human autoimmune trigger, mimics flaring by inducing interferon-related gene (IRG) expression, inflammation, ectopic lymphoid structure (ELS) development, and autoantibody production in the lung that collectively accelerate glomerulonephritis. cSiO2-triggered flaring in this model can be prevented by supplementing mouse diet with the ω-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). A limitation of previous studies was the use of purified diet that, although optimized for rodent health, does not reflect the high American intake of saturated fatty acid (SFA), ω-6 PUFAs, and total fat. To address this, we employed here a modified Total Western Diet (mTWD) emulating the 50th percentile U.S. macronutrient distribution to discern how DHA supplementation and/or SFA and ω-6 reduction influences cSiO2-triggered lupus flaring in female NZBWF1 mice. Six-week-old mice were fed isocaloric experimental diets for 2 wks, intranasally instilled with cSiO2 or saline vehicle weekly for 4 wks, and tissues assessed for lupus endpoints 11 wks following cSiO2 instillation. In mice fed basal mTWD, cSiO2 induced robust IRG expression, proinflammatory cytokine and chemokine elevation, leukocyte infiltration, ELS neogenesis, and autoantibody production in the lung, as well as early kidney nephritis onset compared to vehicle-treated mice fed mTWD. Consumption of mTWD containing DHA at the caloric equivalent to a human dose of 5 g/day dramatically suppressed induction of all lupus-associated endpoints. While decreasing SFA and ω-6 in mTWD modestly inhibited some disease markers, DHA addition to this diet was required for maximal protection against lupus development. Taken together, DHA supplementation at a translationally relevant dose was highly effective in preventing cSiO2-triggered lupus flaring in NZBWF1 mice, even against the background of a typical Western diet.

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<![CDATA[Modulation of T helper 1 and T helper 2 immune balance in a murine stress model during <i>Chlamydia muridarum</i> genital infection]]> https://www.researchpad.co/article/elastic_article_14727 A murine model to study the effect of cold-induced stress (CIS) on Chlamydia muridarum genital infection and immune response has been developed in our laboratory. Previous results in the lab show that CIS increases the intensity of chlamydia genital infection, but little is known about the effects and mechanisms of CIS on the differentiation and activities of CD4+ T cell subpopulations and bone marrow-derived dendritic cells (BMDCs). The factors that regulate the production of T helper 1 (Th1) or T helper 2 (Th2) cytokines are not well defined. In this study, we examined whether CIS modulates the expressions of beta-adrenergic receptor (β-AR), transcription factors, hallmark cytokines of Th1 and Th2, and differentiation of BMDCs during C. muridarum genital infection in the murine model. Our results show that the mRNA level of the beta2-adrenergic receptor (β2-AR) compared to β1-AR and β3-AR was high in the mixed populations of CD4+ T cells and BMDCs. Furthermore, we observed decreased expression of T-bet, low level of Interferon-gamma (IFN-γ) production, increased expression of GATA-3, and Interleukin-4 (IL-4) production in CD4+ T cells of stressed mice. Exposure of BMDCs to Fenoterol, β2-AR agonist, or ICI118,551, β2-AR antagonist, revealed significant β2-AR stimulation or inhibition, respectively, in stressed mice. Moreover, co-culturing of mature BMDCs and naïve CD4+ T cells increased the production of IL-4, IL-10, L-17, and IL-23 cytokines, suggesting that stimulation of β2-AR leads to the increased production of Th2 cytokines. Overall, our results show for the first time that CIS promotes the switching from a Th1 to Th2 cytokine environment. This was evidenced in the murine stress model by the overexpression of GATA-3 concurrent with elevated IL-4 production, reduced T-bet expression, and IFN-γ secretion.

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<![CDATA[Prolyl hydroxylase domain 2 reduction enhances skeletal muscle tissue regeneration after soft tissue trauma in mice]]> https://www.researchpad.co/article/elastic_article_14698 The transcription factor Hypoxia-inducible factor 1 (HIF-1) plays a pivotal role in tissue regeneration. HIF-1 is negatively controlled by O2-dependent prolyl hydroxylases with a predominant role of prolyl hydroxylase 2 isoform (Phd2). Transgenic mice, hypomorphic for this isoform, accumulate more HIF-1 under normoxic conditions. Using these mice, we investigated the influence of Phd2 and HIF-1 on the regenerative capability of skeletal muscle tissue after myotrauma. Phd2-hypomorphic and wild type mice (on C57Bl/6 background) were grouped with regeneration times from 6 to 168 hours after closed mechanic muscle trauma to the hind limb. Tissue samples were analysed by immuno-staining and real-time PCR. Bone marrow derived macrophages of wild type and Phd2-hypomorphic mice were isolated and analysed via flow cytometry and quantitative real-time PCR. Phd2 reduction led to a higher regenerative capability due to enhanced activation of myogenic factors accompanied by induction of genes responsible for glucose and lactate metabolism in Phd2-hypomorphic mice. Macrophage infiltration into the trauma areas in hypomorphic mice started earlier and was more pronounced compared to wild type mice. Phd2-hypomorphic mice also showed higher numbers of macrophages in areas with sustained trauma 72 hours after myotrauma application. In conclusion, we postulate that the HIF-1 pathway is activated secondary to a Phd2 reduction which may lead to i) higher activation of myogenic factors, ii) increased number of positive stem cell proliferation markers, and iii) accelerated macrophage recruitment to areas of trauma, resulting in faster muscle tissue regeneration after myotrauma. With the current development of prolyl hydroxylase domain inhibitors, our findings point towards a potential clinical benefit after myotrauma.

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<![CDATA[Cultural aging stereotypes in European Countries: Are they a risk to Active Aging?]]> https://www.researchpad.co/article/elastic_article_14695 A growing body of literature acknowledges the association between negative stereotypes and individual components of active aging, but very few studies have tested this association, at both individual and population levels. The Stereotypes Content Model (SCM) states that the cultural aging stereotyping of higher warmth than competence (called paternalistic or ambivalent prejudice) is universal. Our aims in this study are to test the extent to which the universality of this stereotype is confirmed in European Countries as well as how far "positive", "negative" or "ambivalent" views towards older people, and other negative attitudes such as prejudice and behaviours such as discrimination, predict active aging assessed both at individual and population levels. We have analyzed data from the European Social Survey-2008 (ESS-2008), containing SCM stereotypical and other appraisal items (such as direct prejudice and perceived discrimination) about adults aged over-70 from 29 European countries. First, SCM cultural stereotypes about older adults (“friendly”, “competent”, and “ambivalent”) were calculated; secondly, after developing a typology of countries based on their “negative”, “ambivalent” and “positive” views about older adults, the universality of cultural stereotypes was tested; thirdly, taking into consideration ESS data of those older persons (over 70s) who self-reported indicators of active aging (health, happiness, satisfaction and social participation), multilevel analyses were performed, taking our inter-individual measure of active aging as dependent variable and our stereotypical classification (positive/negative/ambivalent), direct prejudice and perceived discrimination as predictors; finally, relationships between stereotypical and appraisal items on older adults were examined at population level with country data from Active Aging Indexes. Our results show cultural stereotypes about older people (more friendly than competent) are widespread in most European countries, and negative cultural views of older adults are negatively associated with active aging both at individual and population level, supporting that negative cultural views of older adults could be considered as a threat to active aging.

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<![CDATA[Cytokine signatures of <i>Plasmodium vivax</i> infection during pregnancy and delivery outcomes]]> https://www.researchpad.co/article/elastic_article_14648 Cytokine and growth factor plasma concentrations were evaluated in women from five countries endemic for malaria vivax, at different moments and blood compartments during pregnancy. P. vivax infection during pregnancy was associated with a pro-inflammatory and TH1 response, together with an antiinflammatory response. Nevertheless, at delivery most associations between cytokines and infection were lost. Of note, CCL11/eotaxin, a chemokine not generally analyzed in malaria studies, presented a lower concentration in P. vivax-infected women and a protective association with hemoglobin levels at delivery. Moreover, IL-4 levels had a negative association with birth weight. Data suggest that a compensated inflammatory/antiinflammatory response in P. vivax infection during pregnancy might avoid poor delivery outcomes, while a predominance of TH2 responses may be detrimental for birth weight. Further research is warranted to unravel the role of CCL11 in malaria infection or exposure.

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<![CDATA[Production location of the gelling agent Phytagel has a significant impact on <i>Arabidopsis thaliana</i> seedling phenotypic analysis]]> https://www.researchpad.co/article/elastic_article_14611 Recently, it was found that 1% Phytagel plates used to conduct Arabidopsis thaliana seedling phenotypic analysis no longer reproduced previously published results. This Phytagel, which is produced in China (Phytagel C), has replace American-made Phytagel (Phytagel), which is no longer commercially available. In this study, we present the impact of Phytagel produced in the United States vs. China on seedling phenotypic analysis. As a part of this study, an alternative gelling agent has been identified that is capable of reproducing previously published seedling morphometrics.ResultsPhytagel and Phytagel C were investigated based on their ability to reproduce the subtle phenotype of the sob3-4 esc-8 double mutant. Fluence-rate-response analysis of seedlings grown on 1% Phytagel C plates failed to replicate the sob3-4 esc-8 subtle phenotype seen on 1% Phytagel. Furthermore, root penetrance analysis showed a significant difference between sob3-4 esc-8 seedlings grown on 1% Phytagel and 1% Phytagel C. It was also found that 1% Phytagel C was significantly harder than 1% Phytagel. As a replacement for Phytagel C, Gellan was tested. 1% Gellan was able to reproduce the subtle phenotype of sob3-4 esc-8. Furthermore, there was no significant difference in root penetration of the wild type or sob3-4 esc-8 seedlings between 1% Phytagel and 1% Gellan. This may be due to the significant reduction in hardness in 1% Gellan plates compared to 1% Phytagel plates. Finally, we tested additional concentrations of Gellan and found that seedlings on 0.6% Gellan looked more uniform while also being able to reproduce previously published results.ConclusionsPhytagel has been the standard gelling agent for several studies involving the characterization of subtle seedling phenotypes. After production was moved to China, Phytagel C was no longer capable of reproducing these previously published results. An alternative gelling agent, Gellan, was able to reproduce previously published seedling phenotypes at both 1% and 0.6% concentrations. The information provided in this manuscript is beneficial to the scientific community as whole, specifically phenomics labs, as it details key problematic differences between gelling agents that should be performing identically (Phytagel and Phytagel C). ]]> <![CDATA[Antimicrobial resistance associations with national primary care antibiotic stewardship policy: Primary care-based, multilevel analytic study]]> https://www.researchpad.co/article/elastic_article_14609 Recent UK antibiotic stewardship policies have resulted in significant changes in primary care dispensing, but whether this has impacted antimicrobial resistance is unknown.AimTo evaluate associations between changes in primary care dispensing and antimicrobial resistance in community-acquired urinary Escherichia coli infections.MethodsMultilevel logistic regression modelling investigating relationships between primary care practice level antibiotic dispensing for approximately 1.5 million patients in South West England and resistance in 152,704 community-acquired urinary E. coli between 2013 and 2016. Relationships presented for within and subsequent quarter drug-bug pairs, adjusted for patient age, deprivation, and rurality.ResultsIn line with national trends, overall antibiotic dispensing per 1000 registered patients fell 11%. Amoxicillin fell 14%, cefalexin 20%, ciprofloxacin 24%, co-amoxiclav 49% and trimethoprim 8%. Nitrofurantoin increased 7%. Antibiotic reductions were associated with reduced within quarter same-antibiotic resistance to: amoxicillin, ciprofloxacin and trimethoprim. Subsequent quarter reduced resistance was observed for trimethoprim and amoxicillin. Antibiotic dispensing reductions were associated with increased within and subsequent quarter resistance to cefalexin and co-amoxiclav. Increased nitrofurantoin dispensing was associated with reduced within and subsequent quarter trimethoprim resistance without affecting nitrofurantoin resistance.ConclusionsThis evaluation of a national primary care stewardship policy on antimicrobial resistance in the community suggests both hoped-for benefits and unexpected harms. Some increase in resistance to cefalexin and co-amoxiclav could result from residual confounding. Randomised controlled trials are urgently required to investigate causality. ]]> <![CDATA[A grape seed extract maternal dietary supplementation improves egg quality and reduces ovarian steroidogenesis without affecting fertility parameters in reproductive hens]]> https://www.researchpad.co/article/elastic_article_14599 In broiler hens, the genetic selection increased susceptibility to metabolic disorders and reproductive dysfunctions. In human ovarian cells, grape seed extracts (GSE) improved steroid production. Here, we investigated the effects of a GSE dietary supplementation on egg production and quality, fertility parameters, Reactive Oxygen Species (ROS) and steroid content in yolk egg associated to plasma adipokines in broiler hens. For this, we designed two in vivo experiments, the first one included three groups of hens: A (control), B and C (supplemented with GSE at 0.5% and 1% of the total diet composition, respectively, since week 4), and the second one used two groups of hens: A (control) and D (supplemented with GSE at 1% of the total diet composition since hatching). We assessed the egg production from 23th to 40th weeks and quality at 33th week. After artificial inseminations, the fertility parameters were calculated. In egg yolk, Reactive Oxygen Species (ROS) level and steroid production were evaluated by Ros-Glo H202 and ELISA assay, respectively. Expression of steroidogenic enzymes and adipokines and their receptors was determined by RT-qPCR in ovarian cells and plasma adipokines (RARRES2, ADIPOQ and NAMPT) were evaluated by specific ELISA assays. The fertility parameters and egg production were unaffected by GSE supplementation whatever the experiment (exp.). However, the rate of double-yolk eggs decreased for all GSE supplemented groups (exp. 1 P <0.01, exp.2, P<0.02). In exp.1, C group eggs were bigger and larger (P<0.0001) and the shell elasticity was higher for both B and C (P<0.0003) as compared to control. In the egg yolk, GSE supplementation in both exp. reduced ROS content and steroidogenesis consistent with a decrease in P450 aromatase and StAR mRNA expression and basal in vitro progesterone secretion in granulosa cells (P<0.001). Interestingly, in both exp. RARRES2 plasma levels were positively correlated while ADIPOQ and NAMPT plasma levels were negatively correlated, with steroids and ROS in yolk (P<0.0001). Taken together, maternal dietary GSE supplementation did not affect egg production and fertility parameters whereas it reduced ROS content and steroidogenesis in yolk egg. Furthermore, it ameliorated egg quality by decreasing the number of double-yolk eggs and by improving the size of normal eggs and the elasticity of the shell. Taken together, our data suggest the possibility of using dietary maternal GSE to improve egg quality.

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<![CDATA[COMBSecretomics: A pragmatic methodological framework for higher-order drug combination analysis using secretomics]]> https://www.researchpad.co/article/elastic_article_14596 Multi drug treatments are increasingly used in the clinic to combat complex and co-occurring diseases. However, most drug combination discovery efforts today are mainly focused on anticancer therapy and rarely examine the potential of using more than two drugs simultaneously. Moreover, there is currently no reported methodology for performing second- and higher-order drug combination analysis of secretomic patterns, meaning protein concentration profiles released by the cells. Here, we introduce COMBSecretomics (https://github.com/EffieChantzi/COMBSecretomics.git), the first pragmatic methodological framework designed to search exhaustively for second- and higher-order mixtures of candidate treatments that can modify, or even reverse malfunctioning secretomic patterns of human cells. This framework comes with two novel model-free combination analysis methods; a tailor-made generalization of the highest single agent principle and a data mining approach based on top-down hierarchical clustering. Quality control procedures to eliminate outliers and non-parametric statistics to quantify uncertainty in the results obtained are also included. COMBSecretomics is based on a standardized reproducible format and could be employed with any experimental platform that provides the required protein release data. Its practical use and functionality are demonstrated by means of a proof-of-principle pharmacological study related to cartilage degradation. COMBSecretomics is the first methodological framework reported to enable secretome-related second- and higher-order drug combination analysis. It could be used in drug discovery and development projects, clinical practice, as well as basic biological understanding of the largely unexplored changes in cell-cell communication that occurs due to disease and/or associated pharmacological treatment conditions.

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<![CDATA[Exploring non-assembly 3D printing for novel compliant surgical devices]]> https://www.researchpad.co/article/elastic_article_14586 In minimally invasive surgery, maneuverability is usually limited and a large number of degrees of freedom (DOF) is highly demanded. However, increasing the DOF usually means increasing the complexity of the surgical instrument leading to long fabrication and assembly times. In this work, we propose the first fully 3D printed handheld, multi-steerable device. The proposed device is mechanically actuated, and possesses five serially controlled segments. We designed a new compliant segment providing high torsion and axial stiffness as well as a low bending stiffness by merging the functions of four helicoids and a continuum backbone. Compliant segments were combined to form the compliant shaft of the new device. In order to control this compliant shaft, a control handle was designed that mimics the shaft structure. A prototype called the HelicoFlex was built using only three 3D printed parts. HelicoFlex, with its 10 degrees of freedom, showed a fluid motion in performing single and multi-curved paths. The multi-steerable instrument was 3D printed without any support material in the compliant shaft itself. This work contributes to enlarge the body of knowledge regarding how additive manufacturing could be used in the production of multi-steerable surgical instruments for personalized medicine.

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<![CDATA[Impact of fruit orientation and pelleting material on water uptake and germination performance in artificial substrate for sugar beet]]> https://www.researchpad.co/article/elastic_article_14564 Water uptake into seeds is a fundamental prerequisite of germination and commonly influenced by commercial seed enhancement technologies. The effect of fruit orientation and contrasting pelleting materials on germination and biological performance of sugar beet was assessed. The results indicated there was orientation dependent fruit shrinkage of 37% for the operculum side supplied by moisture compared to 4% for the basal pore side. The expansion rate of 5% compared to the original size, which was also observed for non-shrinking seeds, indicated this was a temporary effect. This behaviour has importance for the application pelleting materials to seeds. Pellets composed of materials exhibiting low levels of swelling act as a water distribution layer which increased germination rates. Careful selection of pelleting material is crucial as it has direct implications on germination speed and subsequent establishment rates.

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<![CDATA[Plasma cytokine profiles in very preterm infants with late-onset sepsis]]> https://www.researchpad.co/article/elastic_article_14557 Deficiencies in innate immune responses may contribute to the increased susceptibility to infection in preterm infants. In vivo cytokine profiles in response to sepsis in very preterm infants are not fully understood.AimsTo characterise plasma pro- and anti-inflammatory cytokine concentrations and pre-defined ratios in very preterm infants with late-onset sepsis (LOS).MethodsIn this observational study, peripheral blood samples were collected at the time of evaluation for suspected LOS from 31 preterm infants (<30 weeks gestational age). Plasma cytokine concentrations were determined by 12-plex immunoassay.ResultsIL-10, IFN-γ, IL-12p70, IP-10, IL-6 and CCL2 were elevated in the majority infants with LOS (n = 12) compared to those without LOS (n = 19). There was no difference in TNF-α, IL-1β, IL-17AF, IL-8 and IL-15 concentrations between groups. IL-10/TNF-α ratios were increased, while CCL2/IL-10 and IL-12p70/IL-10 ratios were decreased in infants with LOS compared to those without.ConclusionVery preterm infants have a marked innate inflammatory response at the time of LOS. The increase in IL-10/TNF-α ratio may indicate early immune hypo-responsiveness. Longitudinal studies with a larger number of participants are required to understand immune responses and clinical outcomes following LOS in preterm infants. ]]>