Mysticism, millenarianism and the visions of Sophia in the works of Jane Lead (1624-1704)

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Perspectives on the Use of Technology as a Home–School Communication and Parent Partnership Tool

Effective communication between home and school is known to increase student achievement. Although technology has the potential to change how schools communicate with parents, most existing research focuses on how schools use technology as a pedagogical tool. The purpose of this generic qualitative study was to address the identified gap in the literature by exploring parent and educator perspectives on how schools and parents could use technology to encourage home–school communication and parent partnership. The conceptual framework included work in parent involvement, student achievement, and using technology as a communication tool. Epstein et al.’s six types of involvement framework was used to develop interview questions and provide a priori coding. Data were collected through semi structured interviews with 10 K-8 educators and five K-12 parents from public schools in Southern California. Yin’s five-stage analytical process was used to compile, disassemble, reassemble, interpret, and present the findings from the data. Four cycles of coding were used: in vivo, descriptive, a priori, and emergent. Key findings include (a) the pandemic has increased the use of technology for teaching, learning, communicating, and parent partnership; (b) parents prefer two-way communication methods; (c) issues of equity are of great concern; and (d) technology can enhance parenting, communicating, volunteering, learning from home, decision making, community collaboration, relationships, and participation at events. This study’s results may effect positive social change by providing data to inform policy and decision making in the areas of technology, communication, and parent partnership. Understanding how educators and parents use technology to foster communication is essential to increasing student achievement through better parent partnership

Performance of point-of-care HbA1c test devices: implications for use in clinical practice – a systematic review and meta-analysis

Regular monitoring of glycated hemoglobin subfraction A1c (HbA1c) in people with diabetes and treatment with glucose-lowering medications to improve glycaemic control can reduce the risk of developing complications [1]. In 2011, a World Health Organization consultation concluded that HbA1cat a threshold of 6.5% (48 mmol/mol) can be used as a diagnostic test for diabetes [2]. HbA1c monitoring often requires the patient to attend the health center twice: once to have blood taken and then returning to get test results and receive adjustments to medication. Point-of-care (POC) analysers are bench-top instruments that use a finger-prick blood sample and are designed for use in a treatment room or at the bed-side. They provide a test result within a few minutes allowing clinical decisions and medication changes to take place immediately. The suitability of many of these devices for the accurate measurement of HbA1c has been questioned, with some POC HbA1c test devices reported not to meet accepted accuracy and precision criteria [3]. Ideal imprecision goals for HbA1c should be coefficient of variation (CV) of <2% for HbA1c reported in % units (or <3% in SI units, mmol/mol) [4], [5], [6]. Most evaluations of POC HbA1c devices have taken place in laboratory settings [7], [8]; fewer studies have assessed device performance in a POC setting or with clinicians performing the tests [9], [10]. The only published review that has attempted to combine data from accuracy studies identified five studies covering three devices and compared correlation coefficients [11]. Systematically reporting and pooling data estimates of bias and precision between POC HbA1c devices and laboratory measurements would enable end users to assess which analysers best meet their analytical performance needs. This may be of particular importance for clinicians in primary care settings where much of the management of diabetes patients takes place. The comparison of accuracy between devices over the entire therapeutic range would need to be carried out by combining data on measurement error (bias) between POC and laboratory tests [12]. The aim of this study was to compare accuracy and precision of POC HbA1c devices with the local laboratory method based on data from published studies and discuss the clinical implications of the findings

Cytosine methylation is a conserved epigenetic feature found throughout the phylum Platyhelminthes

BACKGROUND: The phylum Platyhelminthes (flatworms) contains an important group of bilaterian organisms responsible for many debilitating and chronic infectious diseases of human and animal populations inhabiting the planet today. In addition to their biomedical and veterinary relevance, some platyhelminths are also frequently used models for understanding tissue regeneration and stem cell biology. Therefore, the molecular (genetic and epigenetic) characteristics that underlie trophic specialism, pathogenicity or developmental maturation are likely to be pivotal in our continued studies of this important metazoan group. Indeed, in contrast to earlier studies that failed to detect evidence of cytosine or adenine methylation in parasitic flatworm taxa, our laboratory has recently defined a critical role for cytosine methylation in Schistosoma mansoni oviposition, egg maturation and ovarian development. Thus, in order to identify whether this epigenetic modification features in other platyhelminth species or is a novelty of S. mansoni, we conducted a study simultaneously surveying for DNA methylation machinery components and DNA methylation marks throughout the phylum using both parasitic and non-parasitic representatives. RESULTS: Firstly, using both S. mansoni DNA methyltransferase 2 (SmDNMT2) and methyl-CpG binding domain protein (SmMBD) as query sequences, we illustrate that essential DNA methylation machinery components are well conserved throughout the phylum. Secondly, using both molecular (methylation specific amplification polymorphism, MSAP) and immunological (enzyme-linked immunoabsorbent assay, ELISA) methodologies, we demonstrate that representative species (Echinococcus multilocularis, Protopolystoma xenopodis, Schistosoma haematobium, Schistosoma japonicum, Fasciola hepatica and Polycelis nigra) within all four platyhelminth classes (Cestoda, Monogenea, Trematoda and ‘Turbellaria’) contain methylated cytosines within their genome compartments. CONCLUSIONS: Collectively, these findings provide the first direct evidence for a functionally conserved and enzymatically active DNA methylation system throughout the Platyhelminthes. Defining how this epigenetic feature shapes phenotypic diversity and development within the phylum represents an exciting new area of metazoan biology

Systematic review and metaanalysis comparing the bias and accuracy of the modification of diet in renal disease and chronic kidney disease epidemiology collaboration equations in community-based population

BACKGROUND The majority of patients with chronic kidney disease are diagnosed and monitored in primary care. Glomerular filtration rate (GFR) is a key marker of renal function, but direct measurement is invasive; in routine practice, equations are used for estimated GFR (eGFR) from serum creatinine. We systematically assessed bias and accuracy of commonly used eGFR equations in populations relevant to primary care. CONTENT MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing measured GFR (mGFR) with eGFR in adult populations comparable to primary care and reporting both the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on standardized creatinine measurements. We pooled data on mean bias (difference between eGFR and mGFR) and on mean accuracy (proportion of eGFR within 30% of mGFR) using a random-effects inverse-variance weighted metaanalysis. We included 48 studies of 26875 patients that reported data on bias and/or accuracy. Metaanalysis of within-study comparisons in which both formulae were tested on the same patient cohorts using isotope dilution-mass spectrometry-traceable creatinine showed a lower mean bias in eGFR using CKD-EPI of 2.2 mL/min/1.73 m2 (95% CI, 1.1–3.2; 30 studies; I2 = 74.4%) and a higher mean accuracy of CKD-EPI of 2.7% (1.6–3.8; 47 studies; I2 = 55.5%). Metaregression showed that in both equations bias and accuracy favored the CKD-EPI equation at higher mGFR values. SUMMARY Both equations underestimated mGFR, but CKD-EPI gave more accurate estimates of GFR

Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-κB activation.

Pro-inflammatory cytokine-induced activation of nuclear factor, NF-κB has an important role in leukocyte adhesion to, and subsequent migration across, brain endothelial cells (BECs), which is crucial for the development of neuroinflammatory disorders such as multiple sclerosis (MS). In contrast, microRNA-146a (miR-146a) has emerged as an anti-inflammatory molecule by inhibiting NF-κB activity in various cell types, but its effect in BECs during neuroinflammation remains to be evaluated. Here, we show that miR-146a was upregulated in microvessels of MS-active lesions and the spinal cord of mice with experimental autoimmune encephalomyelitis. In vitro, TNFα and IFNγ treatment of human cerebral microvascular endothelial cells (hCMEC/D3) led to upregulation of miR-146a. Brain endothelial overexpression of miR-146a diminished, whereas knockdown of miR-146a augmented cytokine-stimulated adhesion of T cells to hCMEC/D3 cells, nuclear translocation of NF-κB, and expression of adhesion molecules in hCMEC/D3 cells. Furthermore, brain endothelial miR-146a modulates NF-κB activity upon cytokine activation through targeting two novel signaling transducers, RhoA and nuclear factor of activated T cells 5, as well as molecules previously identified, IL-1 receptor-associated kinase 1, and TNF receptor-associated factor 6. We propose brain endothelial miR-146a as an endogenous NF-κB inhibitor in BECs associated with decreased leukocyte adhesion during neuroinflammation

Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+) T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3(+) T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+) T-cells in PBMC cultures required 'classical' CD14(+) monocytes, which enhanced T-cell activation. CD3(+) T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+) T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease

MicroRNA-155 negatively affects blood-brain barrier function during neuroinflammation.

Blood-brain barrier (BBB) dysfunction is a hallmark of neurological conditions such as multiple sclerosis (MS) and stroke. However, the molecular mechanisms underlying neurovascular dysfunction during BBB breakdown remain elusive. MicroRNAs (miRNAs) have recently emerged as key regulators of pathogenic responses, although their role in central nervous system (CNS) microvascular disorders is largely unknown. We have identified miR-155 as a critical miRNA in neuroinflammation at the BBB. miR-155 is expressed at the neurovascular unit of individuals with MS and of mice with experimental autoimmune encephalomyelitis (EAE). In mice, loss of miR-155 reduced CNS extravasation of systemic tracers, both in EAE and in an acute systemic inflammation model induced by lipopolysaccharide. In cultured human brain endothelium, miR-155 was strongly and rapidly upregulated by inflammatory cytokines. miR-155 up-regulation mimicked cytokine-induced alterations in junctional organization and permeability, whereas inhibition of endogenous miR-155 partially prevented a cytokine-induced increase in permeability. Furthermore, miR-155 modulated brain endothelial barrier function by targeting not only cell-cell complex molecules such as annexin-2 and claudin-1, but also focal adhesion components such as DOCK-1 and syntenin-1. We propose that brain endothelial miR-155 is a negative regulator of BBB function that may constitute a novel therapeutic target for CNS neuroinflammatory disorders

Proceedings of the 2nd BEAT-PCD conference and 3rd PCD training school: part 1

Primary ciliary dyskinesia (PCD) is a rare heterogenous condition that causes progressive suppurative lung disease, chronic rhinosinusitis, chronic otitis media, infertility and abnormal situs. 'Better Experimental Approaches to Treat Primary Ciliary Dyskinesia' (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU funded COST Action (BM1407). The second BEAT-PCD conference, and third PCD training school were held jointly in April 2017 in Valencia, Spain. Presentations and workshops focussed on advancing the knowledge and skills relating to PCD in: basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. Three working groups met to plan consensus statements. Progress with BEAT-PCD projects was shared and new collaborations were fostered. In this report, we summarize the meeting, highlighting developments made during the meeting