Cancer Treatment Helpline:a retrospective study of the NHS Tayside experience

Background Treatment-related toxicity and delays in the management of this toxicity can impact the outcomes of patient with cancer. In Scotland, a national cancer helpline was established to provide triage assessment for patients receiving systemic anticancer therapy (SACT) in an attempt to minimise delays in toxicity management. In this article, we describe the use and impact of the helpline in our region over the last 5 years.Methods Patients who contacted the NHS Tayside cancer helpline between 1 January 2016 and 31 December 2020 were retrospectively identified. Patient demographics as well as the reason and outcome of each call was recorded. A descriptive analysis was performed.Results 6562 individual patients received SACT and 8385 calls were recorded during the time period. Median age of callers was 63 years (range 17–98) and 59.2% were women. Use of the helpline increased by 83.6% between 2016 and 2020, driven by an increase in in-hours calls. 41% of calls required review by a healthcare professional only, 24% required review and admission and the remaining 35% telephone advice only. The majority of cases (85%) were either assessed or advised solely by oncology. The proportional use of general practitioner services has decreased.Conclusions The helpline provides a way for patients to report symptoms directly to their clinical team and receive appropriate specialist advice at an early stage. We demonstrate that most of these calls can be managed solely by our oncology team. This system can reduce pressure on other parts of the local health system

Influence of FK 506 (tacrolimus) on circulating CD4 ⁺ t cells expressing cd25 and cd45ra antigens in 19 patients with chronic progressive multiple sclerosis participating in an open label drug safety trial

We have taken the opportunity of a clinical trial of the potential efficacy and safety of FK 506 (tacrolimus) in chronic progressive multiple sclerosis (MS) to examine the influence of this potent new immunosuppressant on circulating T-lymphocytes in an otherwise healthy non-transplant population. Peripheral blood levels of subsets of CD4+ T lymphocytes expressing the activation molecule interleukin-2 receptor (p55 α chain; CD25) or the CD45RA isoform were determined sequentially in 19 patients that were treated continuously with oral FK 506 (starting dose 0.15 mg/kg/day) for 12 months. No significant change in the proportion of circulating CD25 + CD4+ cells was observed over the study period in which the mean trough plasma FK 506 level rose from 0.3 ±0.2 to 0.5 ±0.4 ng/ml. There was also no significant effect of FK 506 on the percentage of CD45RA + CD4 + cells in the peripheral blood at 12 months compared with pretreatment values. Analysis of a subgroup of 7 patients, who showed a sustained reduction in CD25 + CD4+ cells and a reciprocal increase in CD45RA* CD4 * cells for at least 6 months after start of treatment, did not reveal any difference in disability at one year compared with the treatment group as a whole. The side effects of FK 506 were mild and the overall degree of disability estimated by the mean Kurtzke expanded disability status scale (EDSS) score or the ambulation index did not deteriorate significantly in the 19 patients studied over the 12 months of FK 506 administration. © 1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Forage grasses with lower uptake of casesium and strontium could provide 'safer' crops for radiologically contaminated areas

Substitution of a species or cultivar with higher uptake of an element by one with lower uptake has been proposed as a remediation strategy following accidental releases of radioactivity. However, despite the importance of pasture systems for radiological dose, species/cultivar substitution has not been thoroughly investigated for forage grasses. 397 cultivars from four forage grass species; hybrid ryegrass (Lolium perenne L. x Lolium multiflorum Lam.), perennial ryegrass (Lolium perenne L.), Italian ryegrass (Lolium multiflorum Lam.) and tall fescue (Festuca arundinacea Shreb.); were sampled from 19 field-based breeding experiments in Aberystwyth and Edinburgh (UK) in spring 2013 and analysed for caesium (Cs) and strontium (Sr) concentrations. In order to calculate concentration ratios (CRs; the concentration of an element in a plant in relation to the concentration in the soil), soils from the experiments were also analysed to calculate extractable concentrations of Cs and Sr. To test if cultivars have consistently low Cs and Sr concentration ratios, 17 hybrid ryegrass cultivars were sampled from both sites again in summer 2013 and spring and summer 2014. Tall fescue cultivars had lower Cs and Sr CRs than the other species. Three of the selected 17 hybrid ryegrass cultivars had consistently low Cs CRs, two had consistently low Sr CRs and one had consistently low Cs and Sr CRs. Cultivar substitution could reduce Cs CRs by up to 14-fold and Sr CRs by 4-fold in hybrid ryegrass. The identification of species and cultivars with consistently low CRs suggests that species or cultivar substitution could be an effective remediation strategy for contaminated areas

Multi-scale mechanical characterization of highly swollen photo-activated collagen hydrogels

Biological hydrogels have been increasingly sought after as wound dressings or scaffolds for regenerative medicine, owing to their inherent biofunctionality in biological environments. Especially in moist wound healing, the ideal material should absorb large amounts of wound exudate while remaining mechanically competent in situ. Despite their large hydration, however, current biological hydrogels still leave much to be desired in terms of mechanical properties in physiological conditions. To address this challenge, a multi-scale approach is presented for the synthetic design of cyto-compatible collagen hydrogels with tunable mechanical properties (from the nano- up to the macro-scale), uniquely high swelling ratios and retained (more than 70%) triple helical features. Type I collagen was covalently functionalized with three different monomers, i.e. 4-vinylbenzyl chloride, glycidyl methacrylate and methacrylic anhydride, respectively. Backbone rigidity, hydrogen-bonding capability and degree of functionalization (F: 16 ± 12–91 ± 7 mol%) of introduced moieties governed the structure–property relationships in resulting collagen networks, so that the swelling ratio (SR: 707 ± 51–1996 ± 182 wt%), bulk compressive modulus (Ec: 30 ± 7–168 ± 40 kPa) and atomic force microscopy elastic modulus (EAFM: 16 ± 2–387 ± 66 kPa) were readily adjusted. Because of their remarkably high swelling and mechanical properties, these tunable collagen hydrogels may be further exploited for the design of advanced dressings for chronic wound care

Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors

The Notch protein is one of the most mechanistically direct transmembrane receptors—the intracellular domain contains a transcriptional regulator that is released from the membrane when engagement of the cognate extracellular ligand induces intramembrane proteolysis. We find that chimeric forms of Notch, in which both the extracellular sensor module and the intracellular transcriptional module are replaced with heterologous protein domains, can serve as a general platform for generating novel cell-cell contact signaling pathways. Synthetic Notch (synNotch) pathways can drive user-defined functional responses in diverse mammalian cell types. Because individual synNotch pathways do not share common signaling intermediates, the pathways are functionally orthogonal. Thus, multiple synNotch receptors can be used in the same cell to achieve combinatorial integration of environmental cues, including Boolean response programs, multi-cellular signaling cascades, and self-organized cellular patterns. SynNotch receptors provide extraordinary flexibility in engineering cells with customized sensing/response behaviors to user-specified extracellular cues

A New Rodent Model to Assess Blood Stage Immunity to the Plasmodium falciparum Antigen Merozoite Surface Protein 119 Reveals a Protective Role for Invasion Inhibitory Antibodies

Antibodies capable of inhibiting the invasion of Plasmodium merozoites into erythrocytes are present in individuals that are clinically immune to the malaria parasite. Those targeting the 19-kD COOH-terminal domain of the major merozoite surface protein (MSP)-119 are a major component of this inhibitory activity. However, it has been difficult to assess the overall relevance of such antibodies to antiparasite immunity. Here we use an allelic replacement approach to generate a rodent malaria parasite (Plasmodium berghei) that expresses a human malaria (Plasmodium falciparum) form of MSP-119. We show that mice made semi-immune to this parasite line generate high levels of merozoite inhibitory antibodies that are specific for P. falciparum MSP-119. Importantly, protection from homologous blood stage challenge in these mice correlated with levels of P. falciparum MSP-119–specific inhibitory antibodies, but not with titres of total MSP-119–specific immunoglobulins. We conclude that merozoite inhibitory antibodies generated in response to infection can play a significant role in suppressing parasitemia in vivo. This study provides a strong impetus for the development of blood stage vaccines designed to generate invasion inhibitory antibodies and offers a new animal model to trial P. falciparum MSP-119 vaccines

Whole-genome-wide linkage and IBS/IBD studies

Twelve families with exuberant and early-onset calcium pyrophosphate dehydrate chondrocalcinosis (CC) and diffuse idiopathic skeletal hyperostosis (DISH), hereafter designated DISH/CC, were identified in Terceira Island, the Azores, Portugal. Ninety-two (92) individuals from these families were selected for whole-genome-wide linkage analysis. An identity-by-descent (IBD) analysis was performed in 10 individuals from 5 of the investigated pedigrees. The chromosome area with the maximal logarithm of the odds score (1.32; P=0.007) was not identified using the IBD/identity-by-state (IBS) analysis; therefore, it was not investigated further. From the IBD/IBS analysis, two candidate genes, LEMD3 and RSPO4, were identified and sequenced. Nine genetic variants were identified in the RSPO4 gene; one regulatory variant (rs146447064) was significantly more frequent in control individuals than in DISH/CC patients (P=0.03). Four variants were identified in LEMD3, and the rs201930700 variant was further investigated using segregation analysis. None of the genetic variants in RSPO4 or LEMD3 segregated within the studied families. Therefore, although a major genetic effect was shown to determine DISH/CC occurrence within these families, the specific genetic variants involved were not identified.publishersversionpublishe

Effects of lifestyle interventions on weight amongst Pasifika communities : a systematic review and meta-analysis

Background Pasifika populations experience high incidence and prevalence of obesity and T2DM. However, no international review of lifestyle intervention studies amongst Pasifika communities exists. This study seeks to identify the effect and translatability of lifestyle strategies on weight amongst Pasifika populations. Methods Lifestyle studies involving ≥90% adult Pasifika participants measuring weight change were eligible for inclusion. Database searching was carried out up to December 2021. Databases searched were MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCOhost) and ProQuest Central. Risk of bias was assessed using RoB2 (RCTs) and the National Heart, Lung and Blood Institute (NHLBI) quality assessment tool. Meta-analysis and meta-regression used a bivariate random-effects model. Strategies were coded against pre-identified components of the newly proposed Cultural and Sustainability Assessment of Intervention (CSAI) framework. Findings Twenty-three studies (n = 4258 participants) met inclusion and exclusion criteria. Thirty-two lifestyle strategies targeting weight loss (WL) and 7 targeting weight maintenance (WM) were extracted. Meta-analysis estimates small but significant effect of -0.26 standard deviations (95% CI -0.51 to -0.02), with RCTs demonstrating a non-significant effect of -0.23 standard deviations (95% CI -0.49 to 0.035). Culturally relevant strategies included community and peer support facilitators and team-based activities. The CSAI identified 14 out of 23 studies with low cultural competency and sustainability scores (<60%). Interpretation Qualitative and quantitative analysis show tailored lifestyle interventions has had an estimated small but beneficial effect on WL amongst Pasifika communities. Potential for tailored interventions design to incorporate psychosocial and behavioural considerations. The CSAI has the potential for systematically identifying cultural and sustainability components of efficacy in interventions

Inducible Germline IgMs Bridge Trypanosome Lytic Factor Assembly and Parasite Recognition

Acknowledgments This work was supported by NSF Bread award IOS-1249166 and Hunter College (J.R.); CUNY Science Scholarship (J.V.); Hunter College HHMI UGRAD Science Education grant 52007535 (E.H.); NIH/NIAID award AI085973 (N.P.); Wellcome Trust award 082786 (J.S.). We thank George Cross and Ana Rodriguez for the parasite lines and VSG preparations used in this study.Peer reviewedPostprin