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IntroductionParkinson’s disease (PD) is an incurable, progressive, neurodegenerative disorder. As PD advances and symptoms progress, patients become increasingly dependent on family and carers. Traditional cost-effectiveness analyses (CEA) only consider patient and payer-related outcomes, failing to acknowledge impacts on families, carers, and broader society. This novel Social Return on Investment (SROI) analysis aimed to evaluate the broader impact created by improving access to levodopa (LD) device-aided therapies (DATs) for people living with advanced PD (aPD) in Australia.MethodsA forecast SROI analysis over a three-year time horizon was conducted. People living with aPD and their families were recruited for qualitative interviews or a quantitative survey. Secondary research and clinical trial data was used to supplement the primary research. Outcomes were valued and assessed in a SROI value map in Microsoft Excel™. Financial proxies were assigned to each final outcome based on willingness-to-pay, economic valuation, and replacement value. Treatment cost inputs were sourced from Pharmaceutical Benefits Schedule (PBS) and Medicare Benefits Scheme (MBS) published prices.ResultsTwenty-four interviews were conducted, and 55 survey responses were received. For every $1 invested in access to LD-based DATs in Australia, an estimated $1.79 of social value is created. Over 3 years, it was estimated $277.16 million will be invested and $406.77 million of social return will be created. This value is shared between people living with aPD (27%), their partners (22%), children (36%), and the Australian Government (15%). Most of the value created is social and emotional in nature, including reduced worry, increased connection to family and friends, and increased hope for the future.DiscussionInvestment in LD-based DATs is expected to generate a positive social return. Over 50% of the value is created for the partners and children of people living with aPD. This value would not be captured in traditional CEA. The SROI methodology highlights the importance of investing in aPD treatment, capturing the social value created by improved access to LD-based DATs.

Background Intraplaque angiogenesis occurs in response to atherosclerotic plaque hypoxia, which is driven mainly by highly metabolically active macrophages. Improving plaque oxygenation by increasing macrophage hypoxic signaling, thus stimulating intraplaque angiogenesis, could restore cellular function and neovessel maturation, and decrease plaque formation. Prolyl hydroxylases (PHDs) regulate cellular responses to hypoxia. We therefore aimed to elucidate the role of myeloid PHD2, the dominant PHD isoform, on intraplaque angiogenesis in a murine model for venous bypass grafting. Methods and Results Myeloid PHD2 conditional knockout (PHD2cko) and PHD2 wild type mice on an Ldlr−/− background underwent vein graft surgery (n=11–15/group) by interpositioning donor caval veins into the carotid artery of genotype‐matched mice. At postoperative day 28, vein grafts were harvested for morphometric and compositional analysis, and blood was collected for flow cytometry. Myeloid PHD2cko induced and improved intraplaque angiogenesis by improving neovessel maturation, which reduced intraplaque hemorrhage. Intima/media ratio was decreased in myeloid PHD2cko vein grafts. In addition, PHD2 deficiency prevented dissection of vein grafts and resulted in an increase in vessel wall collagen content. Moreover, the macrophage proinflammatory phenotype in the vein graft wall was attenuated in myeloid PHD2cko mice. In vitro cultured PHD2cko bone marrow–derived macrophages exhibited an increased proangiogenic phenotype compared with control. Conclusions Myeloid PHD2cko reduces vein graft disease and ameliorates vein graft lesion stability by improving intraplaque angiogenesis.

The native extracellular matrix (ECM) contains a host of matricellular proteins and bioactive factors that regulate cell behavior, and many ECM components have been leveraged to guide cell fate. However, the large size and chemical characteristics of these constituents complicate their incorporation into biomaterials without interfering with material properties, motivating the need for alternative approaches to regulate cellular responses. Mesenchymal stromal cells (MSCs) can promote osseous regeneration in vivo directly or indirectly through multiple means including (1) secretion of proangiogenic and mitogenic factors to initiate formation of a vascular template and recruit host cells into the tissue site or (2) direct differentiation into osteoblasts. As MSC behavior is influenced by the properties of engineered hydrogels, we hypothesized that the biochemical and biophysical properties of alginate could be manipulated to promote the dual contributions of encapsulated MSCs toward bone formation. We functionalized alginate with QK peptide to enhance proangiogenic factor secretion and RGD to promote adhesion, while biomechanical-mediated osteogenic cues were controlled by modulating viscoelastic properties of the alginate substrate. A 1:1 ratio of QK:RGD resulted in the highest levels of both proangiogenic factor secretion and mineralization in vitro. Viscoelastic alginate outperformed purely elastic gels in both categories, and this effect was enhanced by stiffness up to 20 kPa. Furthermore, viscoelastic constructs promoted vessel infiltration and bone regeneration in a rat calvarial defect over 12 weeks. These data suggest that modulating viscoelastic properties of biomaterials, in conjunction with dual peptide functionalization, can simultaneously enhance multiple aspects of MSC regenerative potential and improve neovascularization of engineered tissues.

Helicobacter pylori (H. pylori) infects>50% of the world’s population, leading to gastric cancer if left untreated. An estimated 26,000 gastric cancer cases will occur in the US in 2023, with 40% of cases becoming the primary cause of death. Invasive and noninvasive techniques are used to diagnose H. pylori infection; however, controversy exists regarding the “gold standard” for diagnosis. We sought to evaluate the efficacy of H. pylori invasive detection methods: stained biopsy and rapid urease test (RUT) at a single institution. For the study, 200 patients (100 H. pylori + and 100 H. pylori -) from a single institution that underwent gastric biopsies were selected and retrospectively evaluated for H. pylori status. Demographics and clinicopathologic data were collected, including diagnostic tests performed, treatment, and outcomes. Histology and RUT were highly positively and negatively correlative; however, disparate results occurred in 7% of samples which was significant (p95%) and the ability to identify other gastropathies, it should be considered the “gold standard,” for the identification of H. pylori.

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations.

White drupelet disorder (WDD) in blackberry (Rubus subgenus Rubus) is an abiotic condition resulting from a cultivar and environment interaction. Although high temperatures and light intensities have been implicated, little is known why this disorder manifests. Other factors, such as overall plant stress, may be contributing influences. In this study, three treatments were applied to examine whether the addition of nitrogen (N) can reduce WDD on ‘Sweetie Pie’ erect blackberry over three seasons. An initial 50 lb/acre (56.0 kg⋅ha–1) N was applied to all plots at budbreak. Two additional N application treatments of 100 kg⋅ha–1 were applied at one time (1×) or five, 20-kg⋅ha–1 applications (5×), spaced 1 week apart for 5 weeks starting at bloom. One control treatment of no additional N (0×) was also included. Berries were harvested and weighed as a total, then berries with white drupelets were separated out and weighed. The two values were divided to create a proportion and were then multiplied by 100 to determine the percentage. Nitrogen application decreased the percentage of white drupelet berries from 13.0% (control) to 10.0% (one additional application) and 9.1% (five additional applications). WDD for the 0× treatment correlated negatively to maximum high daytime temperatures during May (r = –0.58, P = 0.03) over the three seasons. Occurrence of white drupelets by treatments 0×, 1×, and 5× correlated significantly with the cumulative number of rainfall events (r = 0.49, 0.47, and 0.46, respectively). Leaf chlorophyll index and photosynthesis measurements were unaffected by treatment. Although it is likely that multiple factors are involved in the development of white drupelets, additional N may reduce the problem.

Abstract Background Patients with end-stage kidney disease who receive haemodialysis experience a protracted treatment regimen that can result in an increased risk of depression and anxiety. Arts-based interventions could address this unique issue; however, no arts-based interventions have been developed for delivery within a haemodialysis unit and evaluation within a randomised controlled trials (RCTs). Aim To develop a complex arts-based intervention for patients with end-stage kidney disease whilst receiving haemodialysis. Methods The development process utilised the Arts in Health framework (Fancourt, 2017). The framework was addressed through the establishment of an interdisciplinary advisory group, collaboration and consultation with stakeholders, a scoping and realist review, shadowing of artists-in-residence, personal arts practice and logic modelling. Results The intervention involved six 1-h long, one-to-one facilitated sessions focused on creative writing and visual art. Patients could choose between art form and self-select a subject matter. The sessions had a primary focus on skill development and were delivered using principles derived from the psychological theory of flow. Conclusion The Arts in Health framework provided an appropriate and pragmatic approach to intervention development. Complex arts-based interventions can be developed for the purpose of evaluation within a trial framework. This intervention was designed to strike a balance between standardised components, and a person-centred approach necessary to address existential boredom.

Targeted delivery of anti-inflammatory osteoarthritis treatments have the potential to significantly decrease undesirable systemic side effects and reduce required therapeutic dosage. Here we present a targeted, non-invasive drug delivery system to decrease inflammation in an osteoarthritis model. Hollow thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) nanoparticles have been synthesized via degradation of a N,N'-bis(acryloyl)cystamine (BAC) cross-linked core out of a non-degradable pNIPAM shell. Sulfated 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) was copolymerized in the shell to increase passive loading of an anti-inflammatory mitogen-activated protein kinase-activated protein kinase 2 (MK2)-inhibiting cell-penetrating peptide (KAFAK). The drug-loaded hollow nanoparticles were effective at delivering a therapeutically active dose of KAFAK to bovine cartilage explants, suppressing pro-inflammatory interleukin-6 (IL-6) expression after interleukin-1 beta (IL-1β) stimulation. This thermosensitive hollow nanoparticle system provides an excellent platform for the delivery of peptide therapeutics into highly proteolytic environments such as osteoarthritis.

Characterized by pain, cartilage degradation, and inflammation, osteoarthritis is often treated with anti-inflammatory therapies that provide short-term relief but can have adverse side effects; intra-articular drug delivery systems with controlled release of anti-inflammatory peptides using degradable poly(N-isopropylacrylamide) (pNIPAM) nanoparticles could prolong relief and minimize these side effects. Nanoparticles provide a biocompatible drug carrier that can protect encapsulated therapeutics from enzymatic degradation and increase payload delivery upon encountering a degradation stimulus. Here we demonstrate passive targeting of inflamed cartilage ex vivo by uptake of PEGylated pNIPAM nanoparticles with degradable disulfide crosslinks (abbreviated as NGPEGSS) into chondrocytes and subsequent intracellular release of an anti-inflammatory peptide KAFAKLAARLYRKALARQLGVAA (KAFAK). The KAFAK-loaded NGPEGSS treatment reduced ex vivo inflammation to a greater extent compared to its non-degradable counterparts. This study highlights a nanoparticle system that delivers therapeutics intracellularly with improved efficacy by triggered degradation and suppresses inflammation in multiple cell types within an inflamed joint.

New introductions necessitate ongoing studies to keep producers updated about current trends. Consumer preference study results for poinsettia cultivars may interest breeders, wholesale producers, and retail consumers. An online consumer preference survey, conducted from 15 December 2020 to 19 January 2021, was posted in the Qualtrics software platform. Email distribution lists and Facebook were both used to promote the online survey. The survey link was accompanied by a description introducing the project’s purpose and expressing gratitude for participation. Qualtrics automatically collected participants’ data. The survey was closed, and the data were collected on 19 January 2021 from 792 respondents. This study aimed to identify consumer preferences for traditional red, white, or pink poinsettia cultivars and novelty selections. The topmost preferred poinsettia cultivars are “Princettia Queen Pink”, “Winter Rose Dark Red”, “Ice Punch”, “Christmas Mouse”, “Princettia Pure White”, and “Princettia Hot Pink”. The color of poinsettia cultivars did not significantly affect the respondents’ willingness to pay. However, pot size substantially impacted their willingness to pay for poinsettias. Respondents were willing to pay USD 4.89, 8.13, 12.11, and 17.14 per pot for the 4-, 6-, 8-, and 10-inch potted poinsettias, respectively. Some of the socioeconomic characteristics of the respondents influenced their decisions on how much they were willing to pay for poinsettias.

Abstract Background Haemodialysis can negatively impact quality of life and mental health. Arts-based interventions used successfully in other settings to improve health and well-being, could help address the impact of haemodialysis. This study aimed to evaluate the feasibility and acceptability of conducting a randomised controlled trial (RCT) of an arts-based intervention for patients receiving haemodialysis. Methods A parallel convergent mixed-methods design was used, including a pilot cluster RCT and qualitative process evaluation. Phase 1 evaluated recruitment and retention rates through a pilot cluster RCT at a single haemodialysis unit in Northern Ireland. Participants included patients who received haemodialysis for ESKD, were over the age of 18 and had the capacity to consent. These participants were randomised to the intervention or control group according to their haemodialysis shift. The intervention involved six one-hour, one-to-one facilitated arts sessions during haemodialysis. Phase 2 explored intervention and trial acceptability through a qualitative process evaluation using semi-structured interviews based on the RE-AIM framework. Participants included 13 patients who participated in phase 1 of the study, including 9 participants from the experimental group and four participants from the control group, and nine healthcare professionals who were present on the unit during implementation. Results Out of 122 outpatient haemodialysis patients, 94 were assessed as eligible for participation. Twenty-four participants were randomised, meaning 80% of the target sample size was recruited and the attrition rate at 3 months was 12.5% (n = 3). Participants viewed the arts as more accessible and enjoyable than anticipated following implementation. All participants who started the intervention (n = 11) completed the full six sessions. Qualitative benefits of the intervention suggest improvements in mental well-being. Patient choice and facilitation were important factors for successful implementation. Conclusion An arts-based intervention for patients receiving haemodialysis is acceptable for both patients and healthcare professionals, and a definitive trial is feasible. The intervention may help improve mental-wellbeing in patients receiving haemodialysis, but this requires further investigation in a definitive trial. Trial registration The trial was prospectively registered on clinicaltrials.gov on 14/8/2018, registration number NCT03629496 .

Production of passion fruit (Passiflora sp.) via cuttings is a way to eliminate genetic variation in the crop and also results in a faster establishment time. This could aid producers in increasing production efficiency while maintaining genetic lines. The objective of this research was to evaluate ease of rooting and determine the optimal auxin source for seven species of passion fruit. Semihardwood two-node cuttings were taken from the middle of the parent vine, and auxin treatments were applied to the basal end of the cutting. The cuttings were then stuck to a depth of 1 inch on 20 Aug. 2019. Treatments included three auxin sources and seven passion fruit species. Treatments were set up as a randomized complete block design blocking on species, with 10 single-plant replications per treatment. Data were collected 30 d after sticking cuttings and included percent rooted, total root number, average root length (of the three longest roots, measured in centimeters), root quality (0–5 scale, with 0 = dead and 5 = healthy, vigorous root system), root dry weight (measured in grams), and percent callus. Results showed that passion fruit cuttings receiving a hormone treatment had significantly positive effects on rooting responses, such as increased number, length, quality, and dry weight of roots. Blue passionflower (P. caerulea) was the only species in which hormone treatment did not increase rooting compared with the control. The use of hormone to aid in cutting propagation of passion fruit is recommended, depending on the species being propagated.