Fifth-grade students’ digital retellings and the Common Core: Modal use and design intentionality

Multimodal composing is part of the Common Core vision of the twenty-first-century student. Two descriptive studies were conducted of fifth-grade students’ digital folktale retellings. Study 1 analyzed 83 retellings in relation to the types and frequencies of modal use, such as image, sound, movement, and written text, as well as their retelling accuracy. Students composed within a scaffolded digital composing environment which comprised the PowerPoint authoring/presentation tool and a researcher-developed story frame. All students’ retellings included writing and visual design, 80% included animation, and 70% included sound. Retelling accuracy scores averaged 54%. Study 2 was conducted with a new group of 14 fifth-grade students who had previous digital retelling experience. The retellings included the same types of modal use, but at a higher level of frequency. In their retrospective design interviews, students expressed design intentionality and a metamodal awareness of how modes work together to create an appealing story

Mutations in the Non-Helical Linker Segment L1-2 of Keratin 5 in Patients with Weber-Cockayne Epidermolysis Bullosa Simplex

Keratins are the major structural proteins of the epidermis. Analyzing keratin gene sequences, appreciating the switch in keratin gene expression that takes place as epidermal cells commit to terminally differentiate, and elucidating how keratins assemble into 10 nm filaments, have provided the foundation that has led to the discoveries of the genetic bases of two major classes of human skin diseases, epidermolysis bullosa simplex (EBS) and epidermolytic hyperkeratosis (EH). These diseases involve point mutations in either the basal epidermal keratin pair, K5 and K14 (EBS), or the suprabasal pair, K1 and K10 (EH). In severe cases of EBS and EH, mutations are found in the highly conserved ends of the α-helical rod domain, regions that, by random mutagenesis, had already been found to be important for 10 nm filament assembly. In order to identify regions of the keratin polypeptides that might be more subtly involved in 10 nm filament assembly and to explore the diversity in mutations within milder cases of these diseases, we have focused on Weber-Cockayne EBS, where mild blistering occurs primarily on the hands and feet in response to mechanical stress. In this report, we show that affected members of two different W-C EBS families have point mutations within 1 residue of each other in the non-helical linker segment of the K5 polypeptide. Genetic linkage analyses, the absence of this mutation in \u3e150 wild-type alleles and filament assembly studies suggest that these mutations are responsible for the W-C EBS phenotype. These findings provide the best evidence to date that the non-helical linker region in the middle of the keratin polypeptides plays a subtle but significant role in intermediate filament structure and/or intermediate filament cytoskeletal architecture

An enhanced CRISPR repressor for targeted mammalian gene regulation.

The RNA-guided endonuclease Cas9 can be converted into a programmable transcriptional repressor, but inefficiencies in target-gene silencing have limited its utility. Here we describe an improved Cas9 repressor based on the C-terminal fusion of a rationally designed bipartite repressor domain, KRAB-MeCP2, to nuclease-dead Cas9. We demonstrate the system's superiority in silencing coding and noncoding genes, simultaneously repressing a series of target genes, improving the results of single and dual guide RNA library screens, and enabling new architectures of synthetic genetic circuits

Genetic relationships between Candida albicans strains isolated from dental plaque, trachea, and bronchoalveolar lavage fluid from mechanically ventilated intensive care unit patients

Candida albicans often resides in the oral cavity of healthy humans as a harmless commensal organism. This opportunistic fungus can cause significant disease in critically ill patients, such as those undergoing mechanical ventilation in the intensive care unit (ICU) having compromised local airway defense mechanisms. The goal of this study was to determine the intra- and inter-patient genetic relationship between strains of C. albicans recovered from dental plaque, tracheal secretions, and the lower airway by bronchoalveolar lavage of patients undergoing mechanical ventilation. Three pulsed-field gel electrophoresis (PFGE) typing methods were used to determine the genetic relatedness of the C. albicans strains, including electrophoretic karyotyping (EK) and restriction endonuclease analysis of the genome using SfiI (REAG-S) and BssHII (REAG-B). The C. albicans isolates from dental plaque and tracheo-bronchial sites from the same patient were genetically indistinguishable and retained over time, whereas strains from different patients usually separated into different genotypes. Among the three methods, REAG-B proved to be the most discriminatory method to differentiate isolates. The finding of genetically similar strains from the oral and tracheo-bronchial sites from the same patient supports the notion that the oral cavity may serve as an important source for C. albicans spread to the trachea and lung of mechanically ventilated patients

Non-traditional support workers delivering a brief psychosocial intervention for older people with anxiety and depression: the NOTEPAD feasibility study

ackground: Anxiety and depression often coexist in older people. These disorders are often underdiagnosed and undertreated, and are associated with increased use of health and social care services, and raised mortality. Barriers to diagnosis include the reluctance of older people to present to their general practitioner (GP) with mood symptoms because of the stigma they perceive about mental health problems, and because the treatments offered are not acceptable to them. Objectives: To refine a community-based psychosocial intervention for older people with anxiety and/or depression so that it can be delivered by non-traditional providers such, as support workers (SWs), in the third sector. To determine whether or not SWs can be trained to deliver this intervention to older people with anxiety and/or depression. To test procedures and determine if it is feasible to recruit and randomise patients, and to conduct a process evaluation to provide essential information to inform a randomised trial. Design: Three phases, all informed by a patient and public involvement and engagement group. Qualitative work with older people and third-sector providers, plus a consensus group to refine the intervention, training, SW manuals and patient participant materials (phase 1). Recruitment and training of SWs (phase 2). Feasibility study to test recruitment procedures and assess fidelity of delivery of the intervention; and interviews with study participants, SWs and GPs to assess acceptability of the intervention and impact on routine care (phase 3). Setting: North Staffordshire, in collaboration with Age UK North Staffordshire. © Queen’s Printer and Controller of HMSO 2019. This work was produced by Burroughs et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. vii ABSTRACT viii Intervention: A psychosocial intervention, comprising one-to-one contact between older people with anxiety and/or depression and a SW employed by Age UK North Staffordshire, based on the principles of behavioural activation (BA), with encouragement to participate in a group activity. Results: Initial qualitative work contributed to refinement of the psychosocial intervention. Recruitment (and retention) of the SWs was possible; the training, support materials and manual were acceptable to them, and they delivered the intervention as intended. Recruitment of practices from which to recruit patients was possible, but the recruitment target (100 patients) was not achieved, with 38 older adults randomised. Retention at 4 months was 86%. The study was not powered to demonstrate differences in outcomes. Older people in the intervention arm found the sessions with SWs acceptable, although signposting to, and attending, groups was not valued by all participants. GPs recognised the need for additional care for older people with anxiety and depression, which they could not provide. Participation in the study did not have an impact on routine care, other than responding to the calls from the study team about risk of self-harm. GPs were not aware of the work done by SWs with patients. Limitations: Target recruitment was not achieved. Conclusions: Support workers recruited from Age UK employees can be recruited and trained to deliver an intervention, based on the principles of BA, to older people with anxiety and/or depression. The training and supervision model used in the study was acceptable to SWs, and the intervention was acceptable to older people. Future work: Further development of recruitment strategies is needed before this intervention can be tested in a fully powered randomised controlled trial. Trial registration: Current Controlled Trials ISRCTN16318986. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 7, No. 25. See the NIHR Journals Library website for further project information

Clinical course, characteristics and prognostic indicators in patients presenting with back and leg pain in primary care. The ATLAS study protocol

Low-back related leg pain with or without nerve root involvement is associated with a poor prognosis compared to low back pain (LBP) alone. Compared to the literature investigating prognostic indicators of outcome for LBP, there is limited evidence on prognostic factors for low back-related leg pain including the group with nerve root pain. This 1 year prospective consultation-based observational cohort study will describe the clinical, imaging, demographic characteristics and health economic outcomes for the whole cohort, will investigate differences and identify prognostic indicators of outcome (i.e. change in disability at 12 months), for the whole cohort and, separately, for those classified with and without nerve root pain. In addition, nested qualitative studies will provide insights on the clinical consultation and the impact of diagnosis and treatment on patients' symptom management and illness trajectory

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Canine distemper virus induces apoptosis in cervical tumor derived cell lines

Apoptosis can be induced or inhibited by viral proteins, it can form part of the host defense against virus infection, or it can be a mechanism for viral spread to neighboring cells. Canine distemper virus (CDV) induces apoptotic cells in lymphoid tissues and in the cerebellum of dogs naturally infected. CDV also produces a cytopathologic effect, leading to apoptosis in Vero cells in tissue culture. We tested canine distemper virus, a member of the Paramyxoviridae family, for the ability to trigger apoptosis in HeLa cells, derived from cervical cancer cells resistant to apoptosis. To study the effect of CDV infection in HeLa cells, we examined apoptotic markers 24 h post infection (pi), by flow cytometry assay for DNA fragmentation, real-time PCR assay for caspase-3 and caspase-8 mRNA expression, and by caspase-3 and -8 immunocytochemistry. Flow cytometry showed that DNA fragmentation was induced in HeLa cells infected by CDV, and immunocytochemistry revealed a significant increase in the levels of the cleaved active form of caspase-3 protein, but did not show any difference in expression of caspase-8, indicating an intrinsic apoptotic pathway. Confirming this observation, expression of caspase-3 mRNA was higher in CDV infected HeLa cells than control cells; however, there was no statistically significant change in caspase-8 mRNA expression profile. Our data suggest that canine distemper virus induced apoptosis in HeLa cells, triggering apoptosis by the intrinsic pathway, with no participation of the initiator caspase -8 from the extrinsic pathway. In conclusion, the cellular stress caused by CDV infection of HeLa cells, leading to apoptosis, can be used as a tool in future research for cervical cancer treatment and control

Sonic Hedgehog and Notch Signaling Can Cooperate to Regulate Neurogenic Divisions of Neocortical Progenitors

Innate lymphoid cells (ILCs) and innate-like lymphocytes have important roles in immune responses in the context of infection, cancer, and autoimmunity. The factors involved in driving the differentiation and function of these cell types remain to be clearly defined. There are several cellular signaling pathways involved in embryogenesis, which continue to function in adult tissue. In particular, the WNT, NOTCH, and Hedgehog signaling pathways are emerging as regulators of hematopoietic cell development and differentiation. This review discusses the currently known roles of WNT, NOTCH, and Hedgehog signaling in the differentiation and function of ILCs and innate-like lymphocytes