The soybean Rpp3 gene encodes a TIR-NBS-LRR protein that confers resistance to Phakopsora pachyrhizi.

Soybean rust is an economically significant disease caused by the fungus Phakopsora pachyrhizi that negatively impacts soybean (Glycine max (L.) Merr.) production throughout the world. Susceptible plants infected by P. pachyrhizi develop tan-colored lesions on the leaf surface that give rise to funnel-shaped uredinia as the disease progresses. While most soybean germplasm is susceptible, seven genetic loci (Rpp1 to Rpp7) that provide race-specific resistance to P. pachyrhizi (Rpp) have been identified. Rpp3 was first discovered and characterized in the soybean accession PI 462312 (Ankur), and it was also determined to be one of two Rpp genes present in PI 506764 (Hyuuga). Genetic crosses with PI 506764 were later used to fine-map the Rpp3 locus to a 371 kb region on chromosome 6. The corresponding region in the susceptible Williams 82 (Wm82) reference genome contains several homologous nucleotide binding site-leucine rich repeat (NBS-LRR) genes. To identify Rpp3, we designed oligonucleotide primers to amplify Rpp3 candidate (Rpp3C) NBS-LRR genes at this locus from PI 462312, PI 506764, and Wm82 using polymerase chain reaction (PCR). Five Rpp3C genes were identified in both Rpp3-resistant soybean lines, and co-silencing these genes compromised resistance to P. pachyrhizi. Gene expression analysis and sequence comparisons of the Rpp3C genes in PI 462312 and PI 506764 suggest that a single candidate gene, Rpp3C3, is responsible for Rpp3-mediated resistance.

Administration methods and dosage of poly(lactic acid)-glycol intervention to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalitis mice.

BACKGROUND: Myelin oligodendrocyte glycoprotein-associated disorders (MOGAD) is an autoimmune central nervous system disease. Antigen-specific immune tolerance using nanoparticles such as Polylactic-co-glycolic acid (PLGA) have recently been used as a new therapeutic tolerization approach for CNS autoimmune diseases. We examined whether MOG1-125 conjugated with PLGA could induce MOG-specific immune tolerance in an experimental autoimmune encephalitis (EAE) mouse model. EAE was induced in sixty C57BL/6 J wild-type mice using MOG1-125 peptide with complete Freund's Adjuvant. The mice were divided into 12 groups (n = 5 each) to test the ability of MOG1-125 conjugated PLGA intervention to mitigate the severity or improve the outcomes from EAE with and without rapamycin compared to antigen alone or PLGA alone. EAE score and serum MOG-IgG titers were compared among the interventions.Kindly check and confirm the processed Affiliation “4” is appropriate.I confirmed the Aff 4.Affiliation: Corresponding author information have been changed to present affiliation. Kindly check and confirm.I checked and confirmed the Corresponding author's information. RESULTS: Mice with EAE that were injected intraperitoneally with MOG1-125 conjugated PLGA + rapamycin complex showed dose-dependent mitigation of EAE score. Intraperitoneal and intravenous administration resulted in similar clinical outcomes, whereas 80% of mice treated with subcutaneous injection had a recurrence of clinical score worsening after approximately 1 week. Although there was no significant difference in EAE scores between unconjugated-PLGA and MOG-conjugated PLGA, serum MOG-IgG tended to decrease in the MOG-conjugated PLGA group compared to controls. CONCLUSION: Intraperitoneal administration of PLGA resulted in dose-dependent and longer-lasting immune tolerance than subcutaneous administration. The induction of immune tolerance using PLGA may represent a future therapeutic option for patients with MOGAD.

Expressions of pandemic fatigue on digital platforms: a thematic analysis of sentiment and narratives for infodemic insights.

BACKGROUND: The infodemic accompanying the COVID-19 pandemic has led to an overwhelming amount of information, including questions, concerns and misinformation. Pandemic fatigue has been identified as a concern from early in the pandemic. With new and ongoing health emergencies in 2022, it is important to understand how pandemic fatigue is being discussed and expressed by users on digital channels. This study aims to explore and report on key narrative themes associated with expressions of pandemic fatigue by users on digital platforms. METHODS: This paper describes the collection of publicly available data over a 3-month period from multiple online sources using the Meltwater and CrowdTangle platforms to source data from Twitter, Facebook, Instagram, YouTube, TikTok, Pinterest, Product Reviews, Twitch, blogs & forums. A comprehensive search strategy was developed and tested. A total of 1,484,042 social media posts were identified during the time-period that included the defined search terms for pandemic fatigue. These data were initially sorted by highest levels of engagement and from this dataset, analysts reviewed the identified posts to isolate and remove irrelevant content and identify dominant narratives. A thematic analysis was carried out on these narratives to identify themes related to expression of pandemic fatigue. Two researchers reviewed the data and themes. RESULTS: The thematic analysis of narratives identified six main themes relating to expression of pandemic fatigue, and one theme of counter narratives against pandemic fatigue. Data volume increased concurrent with the time of the mpox emergency announcement. Emergent themes showed the different ways users expressed pandemic fatigue and how it was interlaced with issues of trust, preventative measure acceptance and uptake, misinformation, and being overwhelmed with multiple or sustained emergencies. CONCLUSIONS: This paper has identified the different ways users express pandemic fatigue on digital channels over a 3-month period. Better understanding the implications of the information environment on user's perceptions, questions, and concerns regarding pandemic and more broadly emergency fatigue is vital in identifying relevant interventions and, in the longer term, strengthening the global architecture for health emergency preparedness, prevention, readiness and resilience, as evidenced in this paper. There are clear pathways for further research, including incorporating additional languages and reviewing these themes over longer time periods.

The experiences of gender and sexually diverse parents using support and services for their young children: An integrative review.

AIM: To address: What are the experiences of 2SLGBTQQIA+ parents using parenting supports and services to meet their children's early childhood development needs (<5 years of age)? DESIGN: Whittemore and Knafl's (2005) integrative review methodology. METHODS: Electronic databases were searched from 2000 to October 14, 2022 for empirical studies or reviews addressing the research question. The title and abstract of 12,158 articles were screened for inclusion in the review by two independent researchers; 175 of these articles underwent full-text review. Studies selected were critically appraised using a Joanna Briggs Institute Critical Appraisal tool. Relevant key findings were extracted from each study and entered into N-VIVO-12. Thematic content analysis was employed and PRISMA guidelines were adhered to. RESULTS: A total of 18 articles (15 qualitative and three multi-method studies) met the inclusion criteria and were selected for the review. Seven themes were revealed from analysis of the studies: (1) 2SLGBTQQIA+ Status kept a secret; (2) Forced to come out; (3) Heteronormative messaging; (4) Feeling excluded; (5) Stigmatised; (6) Parents act as educators; and (7) Positive experiences. CONCLUSION: This integrative review provides nurses with insight into the experiences of 2SLGBTQQIA+ parents using health care services for their young child. IMPLICATIONS FOR THE PROFESSION: This article highlights what changes nurses need to make to their practice to ensure appropriate, inclusive care for clients of diverse sexual and gender identities and their families. IMPACT: Health care providers, especially nurses, have an opportunity to improve the experiences of these families and positively impact their health and well-being. Additionally, there is a need for research with the 2SLGBTQQIA+ parent community and the use of rigorous methodological techniques, including clearly linking participants' gender and sexual identities with study findings, to improve our understanding of 2SLGBTQQIA+ parent experiences. PATIENT OR PUBLIC CONTRIBUTION: Although there was no direct patient contribution to the work since it was an integrative review of the literature, indirectly patient contributions are incorporated from the original research results of studies incorporated into this review.

Migrating Mobile Applications to the Web: Adult Crash Cart Training.

Nurses and clinicians require knowledge and training of their facilities' code blue response cart to manage emergency scenarios. However, the nurses who access the carts change frequently through turnover and role changes. An augmented reality training solution was built for mobile devices, but encountered distribution and access challenges. This study evaluated the conversion of the mobile application to a desktop-based version deployed via a learning management system. Eight hundred fifty clinicians were assigned the interactive learning product, which collected anonymous usage data and an optional feedback survey within the module. Of 850 assigned users, 468 completed the module, and 338 completed the feedback survey. Respondents indicated a positive difference of 25.3% in retrospective pre/post confidence and an appreciation for the features of the product. Performance measured by decreasing total item search time appeared to level off after three plays. The format transition was successful, allowing the same widespread distribution as the mobile versions of [X]. Feedback gathered will drive improvements in the module.

Supervised, Self-Administered Tablet-Based Cognitive Assessment in Neurodegenerative Disorders and Stroke.

INTRODUCTION: As the population ages, the prevalence of cognitive impairment is expanding. Given the recent pandemic, there is a need for remote testing modalities to assess cognitive deficits in individuals with neurological disorders. Self-administered, remote, tablet-based cognitive assessments would be clinically valuable if they can detect and classify cognitive deficits as effectively as traditional in-person neuropsychological testing. METHODS: We tested whether the Miro application, a tablet-based neurocognitive platform, measured the same cognitive domains as traditional pencil-and-paper neuropsychological tests. Seventy-nine patients were recruited and then randomized to either undergo pencil-and-paper or tablet testing first. Twenty-nine age-matched healthy controls completed the tablet-based assessments. We identified Pearson correlations between Miro tablet-based modules and corresponding neuropsychological tests in patients and compared scores of patients with neurological disorders with those of healthy controls using t tests. RESULTS: Statistically significant Pearson correlations between the neuropsychological tests and their tablet equivalents were found for all domains with moderate (r > 0.3) or strong (r > 0.7) correlations in 16 of 17 tests (p < 0.05). All tablet-based subtests differentiated healthy controls from neurologically impaired patients by t tests except for the spatial span forward and finger tapping modules. Participants reported enjoyment of the tablet-based testing, denied that it provoked anxiety, and noted no preference between modalities. CONCLUSIONS: This tablet-based application was found to be widely acceptable to participants. This study supports the validity of these tablet-based assessments in the differentiation of healthy controls from patients with neurocognitive deficits in a variety of cognitive domains and across multiple neurological disease etiologies.

Professional care workforce: a rapid review of evidence supporting methods of recruitment, retention, safety, and education.

BACKGROUND: Across the care economy there are major shortages in the health and care workforce, as well as high rates of attrition and ill-defined career pathways. The aim of this study was to evaluate current evidence regarding methods to improve care worker recruitment, retention, safety, and education, for the professional care workforce. METHODS: A rapid review of comparative interventions designed to recruit, retain, educate and care for the professional workforce in the following sectors: disability, aged care, health, mental health, family and youth services, and early childhood education and care was conducted. Embase and MEDLINE databases were searched, and studies published between January 2015 and November 2022 were included. We used the Quality Assessment tool for Quantitative Studies and the PEDro tools to evaluate study quality. RESULTS: 5594 articles were initially screened and after applying the inclusion and exclusion criteria, 30 studies were included in the rapid review. Studies most frequently reported on the professional nursing, medical and allied health workforces. Some studies focused on the single domain of care worker education (n = 11) while most focused on multiple domains that combined education with recruitment strategies, retention strategies or a focus on worker safety. Study quality was comparatively low with a median PEDro score of 5/10, and 77% received a weak rating on the Quality Assessment tool for Quantitative Studies. Four new workforce strategies emerged; early career rural recruitment supports rural retention; workload management is essential for workforce well-being; learning must be contextually relevant; and there is a need to differentiate recruitment, retention, and education strategies for different professional health and care workforce categories as needs vary. CONCLUSIONS: Given the critical importance of recruiting and retaining a strong health and care workforce, there is an immediate need to develop a cohesive strategy to address workforce shortfalls. This paper presents initial evidence on different interventions to address this need, and to inform care workforce recruitment and retention. Rapid Review registration PROSPERO 2022 CRD42022371721 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022371721.

Considerations for the design of overdose education and naloxone distribution interventions: results of a multi-stakeholder workshop.

INTRODUCTION: Opioid overdose epidemic is a public health crisis that is impacting communities around the world. Overdose education and naloxone distribution programs equip and train lay people to respond in the event of an overdose. We aimed to understand factors to consider for the design of naloxone distribution programs in point-of-care settings from the point of view of community stakeholders. METHODS: We hosted a multi-stakeholder co-design workshop to elicit suggestions for a naloxone distribution program. We recruited people with lived experience of opioid overdose, community representatives, and other stakeholders from family practice, emergency medicine, addictions medicine, and public health to participate in a full-day facilitated co-design discussion wherein large and small group discussions were audio-recorded, transcribed and analysed using thematic approaches. RESULTS: A total of twenty-four participants participated in the multi-stakeholder workshop from five stakeholder groups including geographic and setting diversity. Collaborative dialogue and shared storytelling revealed seven considerations for the design of naloxone distribution programs specific to training needs and the provision of naloxone, these are: recognizing overdose, how much naloxone, impact of stigma, legal risk of responding, position as conventional first aid, friends and family as responders, support to call 911. CONCLUSION: To create an naloxone distribution program in emergency departments, family practice and substance use treatment services, stigma is a central design consideration for training and naloxone kits. Design choices that reference the iconography, type, and form of materials associated with first aid have the potential to satisfy the need to de-stigmatize overdose response.

The Marine Natural Compound Dragmacidin D Selectively Induces Apoptosis in Triple-Negative Breast Cancer Spheroids.

Cancer cells grown in 3D spheroid cultures are considered more predictive for clinical efficacy. The marine natural product dragmacidin D induces apoptosis in MDA-MB-231 and MDA-MB-468 triple-negative breast cancer (TNBC) spheroids within 24 h of treatment while showing no cytotoxicity against the same cells grown in monolayers and treated for 72 h. The IC50 for cytotoxicity based on caspase 3/7 cleavage in the spheroid assay was 8 ± 1 µM in MDA-MB-231 cells and 16 ± 0.6 µM in MDA-MB-468 cells at 24 h. No cytotoxicity was seen at all in 2D, even at the highest concentration tested. Thus, the IC50 for cytotoxicity in the MTT assay (2D) in these cells was found to be >75 µM at 72 h. Dragmacidin D exhibited synergy when used in conjunction with paclitaxel, a current treatment for TNBC. Studies into the signaling changes using a reverse-phase protein array showed that treatment with dragmacidin D caused significant decreases in histones. Differential protein expression was used to hypothesize that its potential mechanism of action involves acting as a protein synthesis inhibitor or a ribonucleotide reductase inhibitor. Further testing is necessary to validate this hypothesis. Dragmacidin D also caused a slight decrease in an invasion assay in the MDA-MB-231 cells, although this failed to be statistically significant. Dragmacidin D shows intriguing selectivity for spheroids and has the potential to be a treatment option for triple-negative breast cancer, which merits further research into understanding this activity.

Involving families in the care of Indigenous infants: A philosophical exploration of Indigenous ways of knowing to inform nursing research and practice in the neonatal intensive care unit.

AIMS AND OBJECTIVES: To explore the use of Indigenous philosophies and ways of knowing as a means to critique, understand and improve the care of Indigenous infants and families in the neonatal intensive care unit (NICU). BACKGROUND: The ability of health professionals to provide culturally safe and equitable care to Indigenous infants and their families can affect infant development and long-term health outcomes. Research suggests that family involvement in care benefits both the infant and their family, but there is limited research that addresses the experience of Indigenous families in the NICU and advances understanding of how nurses involve Indigenous families in their infants' care. DESIGN: A discursive, critical review will be presented to outline the assumptions of Indigenous philosophies and to explore how the consideration and implementation of Indigenous ways of knowing can improve the nursing care of Indigenous infants and their families in the NICU. METHOD: First, our subjective positioning as Indigenous nurses and as health researchers is described. Second, our understanding of Indigenous philosophical frameworks and how these approaches fit in the context of the philosophy of science is defined. Third, the key elements of an Indigenous philosophical paradigm are described. Fourth, an application of Indigenous paradigms to supporting the care of Indigenous infants and families in the NICU context is made. CONCLUSIONS: An Indigenous philosophical approach to nursing is ideal for understanding and improving the experiences of Indigenous infants and families in the NICU. This approach allows nurses to critically analyse the history and legacy of colonialism and its impact on the health and wellbeing of Indigenous peoples. By prioritising the voices and concerns of Indigenous families in the clinical setting and in nursing research, nurses can better understand the experiences of these families in the NICU and use strengths-based approaches to facilitate family involvement in care. RELEVANCE TO CLINICAL PRACTICE: The application of Indigenous philosophies in the nursing context can be used to inform the care of Indigenous infants and families in the NICU. Potential benefits include improved therapeutic relationships between nurses and Indigenous families, and increased uptake of parent-led interventions in nursing practice, which may lead to improved health outcomes for Indigenous infants in the NICU and throughout their subsequent development.

The Unexpected Benefits of a Decolonized Knowledge Translation Initiative for Indigenous Mother Participants.

Western health research's approach to knowledge translation (KT) has been criticized by Indigenous scholars, leaders, and communities for its misalignment with Indigenous ways of knowing and relational approaches to sharing knowledge. Conversely, Indigenous KT is understood as 'sharing what we know about living a good life' (Kaplan-Myrth & Smylie, 2006). Whereas KT in Euro-Western science contexts focuses on closing the know-do gap implying a separation of knowledge and action, knowledge in the Indigenous context is inherently practical and based on centuries old practices including oral traditions, experiential knowledge, and cross-cultural sharing. This article describes the development of a decolonized KT strategy. This community-engaged KT initiative was developed at the suggestion of Indigenous mothers who participated in a research study in Hamilton, Canada, which examined their experiences using health care to meet the health needs of their infants. Indigenous mothers participated in three main roles related to the KT activities: sharing their story in video, participating as team members on an Advisory Board, and directing the creation of a video series and website educational resource (KT strategy). Five Indigenous mothers participated as members of the Advisory Board. The process of participating had positive impacts on the mothers, namely, empowerment, strength, 'I am not alone', and healing. These unexpected findings, which go beyond the original project purpose to create an educational resource, show the significant and important benefits for research participants, particularly those from Indigenous communities, to be involved in decolonized KT strategies.

Upregulated complement receptors correlate with Fc gamma receptor 3A-positive natural killer and natural killer-T cells in neuromyelitis optica spectrum disorder.

BACKGROUND AND OBJECTIVES: Inhibition of terminal complement in neuromyelitis optica spectrum disorder (NMOSD) using eculizumab helps prevent relapses, but the exact mechanism of action of the drug remains unclear. Similarly, genetic variants in the Fc Gamma receptor 3A (FCGR3A), also known as CD16, are correlated with outcomes in NMOSD, but the immune cells expressing those CD16 are unknown. We compared CD16 expression on immune cells modulated by complement activity in natural killer (NK) cells and natural killer-T (NKT) cells in NMOSD to disease and normal-healthy controls. METHODS: Peripheral blood cell (PBMC) samples from 45 patients with NMOSD with aquaporin 4 (AQP4)-IgG, 18 disease controls, and 19 normal controls were analyzed for CD16 expression and complement receptors in vitro. RESULTS: At baseline, the number of NKT cells was increased in NMOSD (p < 0.001), but the proportion that was CD16 positive was lower compared to normal and disease controls (p = 0.0012). NK cell count was normal, but the ratio that was CD16 positive was also significantly lower (p < 0.001). In both NK cells and NKT cells from NMOSD, C5 complement receptor expression was much higher than normal and disease controls (p < 0.001 for both). We also evaluated activation markers CD69 and CD83, which were also significantly higher in NK and NKT cells from NMOSD patients. FCGR3A p158 V/V genotype group in NMOSD patients showed decreased NK cell proportion with activation, and fewer CD16-expressing NKT cells than the F/F genotype group. DISCUSSION: Our results support an immunopathogenesis model in which complement pathway activation in NK/NKT cells upregulates CD16 expression that binds to antibody/antigen complexes. In the context of NMOSD, these complement-sensitive cells may be responsible for the escalating autoimmune activity.

Validation of a Mobile, Sensor-based Neurobehavioral Assessment With Digital Signal Processing and Machine-learning Analytics.

BACKGROUND: The Miro Health Mobile Assessment Platform consists of self-administered neurobehavioral and cognitive assessments that measure behaviors typically measured by specialized clinicians. OBJECTIVE: To evaluate the Miro Health Mobile Assessment Platform's concurrent validity, test-retest reliability, and mild cognitive impairment (MCI) classification performance. METHOD: Sixty study participants were evaluated with Miro Health version V.2. Healthy controls (HC), amnestic MCI (aMCI), and nonamnestic MCI (naMCI) ages 64-85 were evaluated with version V.3. Additional participants were recruited at Johns Hopkins Hospital to represent clinic patients, with wider ranges of age and diagnosis. In all, 90 HC, 21 aMCI, 17 naMCI, and 15 other cases were evaluated with V.3. Concurrent validity of the Miro Health variables and legacy neuropsychological test scores was assessed with Spearman correlations. Reliability was quantified with the scores' intraclass correlations. A machine-learning algorithm combined Miro Health variable scores into a Risk score to differentiate HC from MCI or MCI subtypes. RESULTS: In HC, correlations of Miro Health variables with legacy test scores ranged 0.27-0.68. Test-retest reliabilities ranged 0.25-0.79, with minimal learning effects. The Risk score differentiated individuals with aMCI from HC with an area under the receiver operator curve (AUROC) of 0.97; naMCI from HC with an AUROC of 0.80; combined MCI from HC with an AUROC of 0.89; and aMCI from naMCI with an AUROC of 0.83. CONCLUSION: The Miro Health Mobile Assessment Platform provides valid and reliable assessment of neurobehavioral and cognitive status, effectively distinguishes between HC and MCI, and differentiates aMCI from naMCI.

Design details for overdose education and take-home naloxone kits: Codesign with family medicine, emergency department, addictions medicine and community.

INTRODUCTION: Overdose education and naloxone distribution (OEND) programmes equip and train people who are likely to witness an opioid overdose to respond with effective first aid interventions. Despite OEND expansion across North America, overdose rates are increasing, raising questions about how to improve OEND programmes. We conducted an iterative series of codesign stakeholder workshops to develop a prototype for take-home naloxone (THN)-kit (i.e., two doses of intranasal naloxone and training on how to administer it). METHODS: We recruited people who use opioids, frontline healthcare providers and public health representatives to participate in codesign workshops covering questions related to THN-kit prototypes, training on how to use it, and implementation, including refinement of design artefacts using personas and journey maps. Completed over 9 months, the workshops were audio-recorded and transcribed with visible results of the workshops (i.e., sticky notes, sketches) archived. We used thematic analyses of these materials to identify design requirements for THN-kits and training. RESULTS: We facilitated 13 codesign workshops to identify and address gaps in existing opioid overdose education training and THN-kits and emphasize timely response and stigma in future THN-kit design. Using an iterative process, we created 15 prototypes, 3 candidate prototypes and a final prototype THN-kit from the synthesis of the codesign workshops. CONCLUSION: The final prototype is available for a variety of implementation and evaluation processes. The THN-kit offers an integrated solution combining ultra-brief training animation and physical packaging of nasal naloxone to be distributed in family practice clinics, emergency departments, addiction medicine clinics and community settings. PATIENT OR PUBLIC CONTRIBUTION: The codesign process was deliberately structured to involve community members (the public), with multiple opportunities for public contribution. In addition, patient/public participation was a principle for the management and structuring of the research team.

High-Throughput Screening of a Marine Compound Library Identifies Anti-Cryptosporidium Activity of Leiodolide A.

Cryptosporidium sp. are apicomplexan parasites that cause significant morbidity and possible mortality in humans and valuable livestock. There are no drugs on the market that are effective in the population most severely affected by this parasite. This study is the first high-throughput screen for potent anti-Cryptosporidium natural products sourced from a unique marine compound library. The Harbor Branch Oceanographic Institute at Florida Atlantic University has a collection of diverse marine organisms some of which have been subjected to medium pressure liquid chromatography to create an enriched fraction library. Numerous active compounds have been discovered from this library, but it has not been tested against Cryptosporidium parvum. A high-throughput in vitro growth inhibition assay was used to test 3764 fractions in the library, leading to the identification of 23 fractions that potently inhibited the growth of Cryptosporidium parvum. Bioassay guided fractionation of active fractions from a deep-sea sponge, Leiodermatium sp., resulted in the purification of leiodolide A, the major active compound in the organism. Leiodolide A displayed specific anti-Cryptosporidium activity at a half maximal effective concentration of 103.5 nM with selectivity indexes (SI) of 45.1, 11.9, 19.6 and 14.3 for human ileocecal colorectal adenocarcinoma cells (HCT-8), human hepatocellular carcinoma cells (Hep G2), human neuroblastoma cells (SH-SY5Y) and green monkey kidney cells (Vero), respectively. The unique structure of leiodolide A provides a valuable drug scaffold on which to develop new anti-Cryptosporidium compounds and supports the importance of screening natural product libraries for new chemical scaffolds.

Action research with caseworkers: Responding to and reflecting on the impacts of COVID-19 on birth family contact.

Social distancing due to COVID-19 forced changes to contact with birth relatives for children in out-of-home care. This required a shift to using technologies, which was previously underutilized and viewed as risky. In an action research study, 33 caseworkers in New South Wales, Australia, reflected upon adapting their practices. Three key themes characterized the changes in caseworker practices and how these impacted upon social interactions between children and their birth and carer families: communication, not location; shared not separate spaces and spontaneous not restricted interaction. First, caseworkers described how contact via technologies involved fewer logistical arrangements, shifting the focus on interactions among children and their two families and encouraging these to be flexible and child-centred. Second, caseworkers discussed how spending time together virtually could build trust, as carers and birth relatives could forge relationships around shared commitment to the child's wellbeing. Third, caseworkers noted that technology-facilitated communication enabled greater choice and control for children while requiring renegotiating boundaries. The findings reflect a shift in caseworker perceptions of technology-facilitated contact from a risk to opportunity framework as a result of COVID-19 conditions, consistent with social shaping of technology theory. Beyond the pandemic, contact with birth relatives can be enhanced through technology.

Effect of combined home-based, overground robotic-assisted gait training and usual physiotherapy on clinical functional outcomes in people with chronic stroke: A randomized controlled trial.

OBJECTIVES: To assess the effect of a home-based over-ground robotic-assisted gait training program using the AlterG Bionic Leg orthosis on clinical functional outcomes in people with chronic stroke. DESIGN: Randomized controlled trial. SETTING: Home. PARTICIPANTS: Thirty-four ambulatory chronic stroke patients who recieve usual physiotherapy. INTERVENTION: Usual physiotherapy plus either (1)10-week over-ground robotic-assisted gait training program (n = 16), using the device for ⩾30 minutes per day, or (2) control group (n = 18), 30 minutes of physical activity per day. MEASUREMENTS: The primary outcome was the Six-Minute Walk Test. Secondary outcomes included: Timed-Up-and-Go, Functional Ambulation Categories, Dynamic Gait Index and Berg Balance Scale. Physical activity and sedentary time were assessed using accelerometry. All measurements were completed at baseline, 10 and 22 weeks after baseline. RESULTS: Significant increases in walking distance were observed for the Six-Minute Walk Test between baseline and 10 weeks for over-ground robotic-assisted gait training (135 ± 81 m vs 158 ± 93 m, respectively; P ⩽ 0.001) but not for control (122 ± 92 m vs 119 ± 84 m, respectively). Findings were similar for Functional Ambulation Categories, Dynamic Gait Index and Berg Balance Scale (all P ⩽ 0.01). For over-ground robotic-assisted gait training, there were increases in time spent stepping, number of steps taken, number of sit-to-stand transitions, and reductions in time spent sitting/supine between baseline and 10 weeks (all P < 0.05). The differences observed in all of the aforementioned outcome measures were maintained at 22 weeks, 12 weeks after completing the intervention (all P > 0.05). CONCLUSION: Over-ground robotic-assisted gait training combined with physiotherapy in chronic stroke patients led to significant improvements in clinical functional outcomes and physical activity compared to the control group. Improvements were maintained at 22 weeks.

Improving the uptake of Kangaroo Mother Care in neonatal units: A narrative review and conceptual framework.

Kangaroo Mother Care is a beneficial intervention for high-risk infants; however, global uptake is lacking. Recent systematic reviews have collated the numerous studies that identify diverse barriers and enablers to the use of Kangaroo Mother Care. In this narrative review, we combine the findings of these systematic reviews with more recent studies to propose a conceptual framework, encompassing factors that may affect the initiation and maintenance of Kangaroo Mother Care in neonatal units. CONCLUSION: This conceptual framework includes parental, healthcare professional, and healthcare system factors, and highlights the potential interplay between them. In line with this, we suggest strategies to improve the uptake of Kangaroo Mother Care in neonatal units.

The Marine Natural Product Furospinulosin 1 Induces Apoptosis in MDA-MB-231 Triple Negative Breast Cancer Cell Spheroids, But Not in Cells Grown Traditionally with Longer Treatment.

Cancer cells grown in spheroid conditions interact with each other and the extracellular matrix, providing a better representation of the in vivo environment than two-dimensional cultures and are a more clinically relevant model. A discrete screening of genetically diverse marine samples in the spheroid assay led to the identification of a novel activity for the known compound furospinulosin 1. This compound shows activity against MDA-MB-231 triple negative breast cancer cells grown as spheroids and treated for 24 or 48 h. No cytotoxicity was seen in traditional two-dimensional adherent cultures treated for a longer time (72 h). A reverse phase protein array (RPPA) confirmed the limited activity of the compound in cells grown traditionally and revealed changes in protein expression when cells are grown as spheroids that are associated with better clinical prognosis. Analysis of the RPPA data through the Broad institute's connectivity map suggested the hypothesis that furospinulosin 1 functions as an MEK inhibitor. Analysis of the RPPA data through STRING supports the apoptosis observed. The selectivity exhibited by furospinulosin 1 for triple negative breast cancer cells only when grown as spheroids makes it an interesting compound with strong therapeutic potential that merits further study.

Discovery of Survivin Inhibitors Part 1: Screening the Harbor Branch Pure Compound Library.

Survivin is a 16.5 KDa protein whose functions include promoting cellular mitosis, angiogenesis, and senescence as well as inhibiting apoptosis. Higher survivin expression is found in cancer tissues than normal tissues, and this expression correlates with disease progression and aggressiveness. Survivin has been validated as a clinical target for cancer. Small molecules are important antagonists of survivin levels in cancer cells. A structurally diverse library of genetically encoded small molecules (natural products) derived from marine plants, invertebrates, and microbes was screened for their ability to reduce expression levels of survivin in the DLD-1 colon adenocarcinoma and the A549 nonsmall cell lung carcinoma cell lines. This led to the identification of this novel activity for the known compounds eryloside E, ilicicolin H, tanzawaic acid A, and p-hydroxyphenopyrrozin. Both eryloside E and ilicicolin H showed the ability to reduce survivin expression in the low micromolar range against both cell lines.