Use of a Hybrid Adeno-Associated Viral Vector Transposon System to Deliver the Insulin Gene to Diabetic NOD Mice.

Previously, we used a lentiviral vector to deliver furin-cleavable human insulin (INS-FUR) to the livers in several animal models of diabetes using intervallic infusion in full flow occlusion (FFO), with resultant reversal of diabetes, restoration of glucose tolerance and pancreatic transdifferentiation (PT), due to the expression of beta (β)-cell transcription factors (β-TFs). The present study aimed to determine whether we could similarly reverse diabetes in the non-obese diabetic (NOD) mouse using an adeno-associated viral vector (AAV) to deliver INS-FUR ± the β-TF Pdx1 to the livers of diabetic mice. The traditional AAV8, which provides episomal expression, and the hybrid AAV8/piggyBac that results in transgene integration were used. Diabetic mice that received AAV8-INS-FUR became hypoglycaemic with abnormal intraperitoneal glucose tolerance tests (IPGTTs). Expression of β-TFs was not detected in the livers. Reversal of diabetes was not achieved in mice that received AAV8-INS-FUR and AAV8-Pdx1 and IPGTTs were abnormal. Normoglycaemia and glucose tolerance were achieved in mice that received AAV8/piggyBac-INS-FUR/FFO. Definitive evidence of PT was not observed. This is the first in vivo study using the hybrid AAV8/piggyBac system to treat Type 1 diabetes (T1D). However, further development is required before the system can be used for gene therapy of T1D

Dynamic Angular Petrissage as Treatment for Axillary Web Syndrome Occurring after Surgery for Breast Cancer: a Case Report

Background: In the context of breast cancer, axillary web syndrome (AWS), also called lymphatic cording, typically presents in the weeks after axillary surgery. This painful condition, likely lymphofibrotic in origin, restricts upper extremity range of motion (ROM). There is no established treatment, although physical therapy and other approaches have been used to variable effect. This report describes treatment of a female client with AWS, who had recently undergone a unilateral simple mastectomy with sentinel node biopsy plus axillary dissection.Methods: The client presented with pain upon movement (self-reported as 5 on the 0–10 Oxford Pain Scale), visible cording and restricted use of the ipsilateral upper extremity. Clinical assessment included determining the extent of AWS cording (taut, from axilla to wrist) and measuring glenohumeral joint ROM (140° flexion by goniometer). A therapeutic massage with movement protocol, termed dynamic angular petrissage, was administered over two sessions: Swedish massage combined with dynamically taking the limb through all possible angles of movement (passive ROM), controlling stretch and tension while simultaneously and segmentally applying petrissage and non-petrissage techniques to the underlying soft tissue. Careful attention was taken to not break the cord. Home care consisted of prescribed exercises performed by the patient.Results: After Session One, pain was reduced (to 0/10), ROM improved (to 170° flexion), and cording was visibly reduced. After Session Two the cord was residually apparent only on hyperextension, with no ROM restrictions in glenohumeral joint flexion. Follow-up at three months revealed absence of visual or palpable evidence of cording, unrestricted glenohumeral joint ROM, and absence of movement-associated pain.Conclusion: The signs and symptoms of AWS were quickly and effectively eliminated, without causing any pain or discomfort to the client. We propose that dynamic angular petrissage may be an efficient and safe treatment approach for reducing the pain, mobility restrictions, and cording of AWS

A Quantitative Analytical Method to Test for Salt Effects on Giant Unilamellar Vesicles

Today, free-standing membranes, i.e. liposomes and vesicles, are used in a multitude of applications, e.g. as drug delivery devices and artificial cell models. Because current laboratory techniques do not allow handling of large sample sizes, systematic and quantitative studies on the impact of different effectors, e.g. electrolytes, are limited. In this work, we evaluated the Hofmeister effects of ten alkali metal halides on giant unilamellar vesicles made of palmitoyloleoylphosphatidylcholine for a large sample size by combining the highly parallel water-in-oil emulsion transfer vesicle preparation method with automatic haemocytometry. We found that this new quantitative screening method is highly reliable and consistent with previously reported results. Thus, this method may provide a significant methodological advance in analysis of effects on free-standing model membranes

Dietary zinc and the control of Streptococcus pneumoniae infection

© 2019 Eijkelkamp et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Human zinc deficiency increases susceptibility to bacterial infection. Although zinc supplementation therapies can reduce the impact of disease, the molecular basis for protection remains unclear. Streptococcus pneumoniae is a major cause of bacterial pneumonia, which is prevalent in regions of zinc deficiency. We report that dietary zinc levels dictate the outcome of S. pneumoniae infection in a murine model. Dietary zinc restriction impacts murine tissue zinc levels with distribution post-infection altered, and S. pneumoniae virulence and infection enhanced. Although the activation and infiltration of murine phagocytic cells was not affected by zinc restriction, their efficacy of bacterial control was compromised. S. pneumoniae was shown to be highly sensitive to zinc intoxication, with this process impaired in zinc restricted mice and isolated phagocytic cells. Collectively, these data show how dietary zinc deficiency increases sensitivity to S. pneumoniae infection while revealing a role for zinc as a component of host antimicrobial defences

The impact of libraries as creative spaces

Ready access to information through digital media has challenged the perceived societal roles of public libraries. Since the mid 1990s, libraries have reoriented themselves towards public participation beyond lending and reading. Libraries now offer an increasing range of community-focused creative activities.Library spaces are transforming. In addition to housing archival and loan materials, desks and reading spaces, libraries are becoming even more exible and activity-oriented. Given these transformations, understanding and demonstrating the new contributions public libraries make to their communities is critical.In 2015, the State Library of Queensland (SLQ) commissioned researchers at the Digital Media Research Centre at Queensland University of Technology (QUT) to explore the impact of libraries as creative spaces.The objectives of the Libraries as Creative Spaces project were to:• Investigate the community impact of creative spaces in public libraries• Provide clear evidence of this impact• Articulate the opportunities to further embed creative spaces in public libraries or community spaces.The methods used included:• A contextual review of thinking regarding libraries as creative spaces• A literature review on the evaluation of creative activity in libraries and creative spaces more generally• Interviews and observational eld research at selected Queensland libraries• The development and refinement of an evidence-based Creative Spaces Impact Framework• The development of an associated rich media package (including videos, photos and digital stories) showcasing library-based creative activity across Queensland in 2015.The contextual review highlights the attention being paid to makerspaces as a site of creative activity in public libraries. However, the review also points to the many other ways public libraries are facilitating creative activity. It also demonstrates that while libraries have been formally evaluated for more than a hundred years, only recently has there been a concerted e ort to develop frameworks that can qualitatively assess the social impact on individuals and their communities. Moreover, few of these frameworks directly assess libraries as creative spaces.Following the contextual review, an extended literature review was undertaken for two reasons. Firstly, to develop our understanding of how creative spaces are evaluated (outside the library context). And secondly, to develop our understanding of how libraries are evaluated in more general terms. From this initial evidence base, a preliminary Creative Spaces Impact Framework was developed.The framework was used to interrogate creative activity at ve public library sites across Queensland – Ayr, Cleveland, Helensvale, Roma, and Victoria Point. The framework was revised in conjunction with the eldwork and further feedback from a range of stakeholders. The Creative Spaces Impact Framework allows for the evaluation of libraries as creative spaces through the creative activities they enable. These activities may be formally organised by the library, informally enacted by library clients, or involve a combination of both approaches. The contents of the framework represent a range of impact potentials, some of which will be relevant to certain library creative space activities more than others, if at all

A roadmap to advance delirium research: recommendations from the NIDUS Scientific Think Tank

Delirium is an acute disorder of attention and cognition. It occurs across the life span, yet it is particularly common among older adults, and is closely linked with underlying neurocognitive disorders. Evidence is mounting that intervening on delirium may represent an important opportunity for delaying the onset or progression of dementia. To accelerate the current understanding of delirium, the Network for Investigation of Delirium: Unifying Scientists (NIDUS) held a conference “Advancing Delirium Research: A Scientific Think Tank” in June 2019. This White Paper encompasses the major knowledge and research gaps identified at the conference: advancing delirium definition and measurement, understanding delirium pathophysiology, and prevention and treatment of delirium. A roadmap of research priorities is proposed to advance the field in a systematic, interdisciplinary, and coordinated fashion. A call is made for an international consortium and biobank targeted to delirium, as well as a public health campaign to advance the field.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155509/1/alz12076_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155509/2/alz12076.pd

Learning auditory space: generalization and long-term effects

Background: Previous findings have shown that humans can learn to localize with altered auditory space cues. Here we analyze such learning processes and their effects up to one month on both localization accuracy and sound externalization. Subjects were trained and retested, focusing on the effects of stimulus type in learning, stimulus type in localization, stimulus position, previous experience, externalization levels, and time. Method: We trained listeners in azimuth and elevation discrimination in two experiments. Half participated in the azimuth experiment first and half in the elevation first. In each experiment, half were trained in speech sounds and half in white noise. Retests were performed at several time intervals: just after training and one hour, one day, one week and one month later. In a control condition, we tested the effect of systematic retesting over time with post-tests only after training and either one day, one week, or one month later. Results: With training all participants lowered their localization errors. This benefit was still present one month after training. Participants were more accurate in the second training phase, revealing an effect of previous experience on a different task. Training with white noise led to better results than training with speech sounds. Moreover, the training benefit generalized to untrained stimulus-position pairs. Throughout the post-tests externalization levels increased. In the control condition the long-term localization improvement was not lower without additional contact with the trained sounds, but externalization levels were lower. Conclusion: Our findings suggest that humans adapt easily to altered auditory space cues and that such adaptation spreads to untrained positions and sound types. We propose that such learning depends on all available cues, but each cue type might be learned and retrieved differently. The process of localization learning is global, not limited to stimulus-position pairs, and it differs from externalization processes.Foundation for Science and TechnologyFEDE

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

Chronic Leukemias

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66325/1/j.1365-4362.1982.tb03146.x.pd