Protocol: inspiratory muscle training for promoting recovery and outcomes in ventilated patients (IMPROVe): a randomised controlled trial

Introduction: Inspiratory muscle weakness is a known consequence of mechanical ventilation and a potential contributor to difficulty in weaning from ventilatory support. Inspiratory muscle training (IMT) reduces the weaning period and increases the likelihood of successful weaning in some patients. However, it is not known how this training affects the residual inspiratory muscle fatigability following successful weaning nor patients' quality of life or functional outcomes. Methods and analysis: This dual centre study includes two concurrent randomised controlled trials of IMT in adult patients who are either currently ventilator-dependent (>7 days) (n=70) or have been recently weaned from mechanical ventilation (>7 days) in the past week (n=70). Subjects will be stable, alert and able to actively participate and provide consent. There will be concealed allocation to either treatment (IMT) or usual physiotherapy (including deep breathing exercises without a resistance device). Primary outcomes are inspiratory muscle fatigue resistance and maximum inspiratory pressures. Secondary outcomes are quality of life (Short Form-36v2, EQ-5D), functional status (Acute Care Index of Function), rate of perceived exertion (Borg Scale), intensive care length of stay (days), post intensive care length of stay (days), rate of reintubation (%) and duration of ventilation (days). Ethics and dissemination: Ethics approval has been obtained from relevant institutions, and results will be published with a view to influencing physiotherapy practice in the management of long-term ventilator-dependent patients to accelerate weaning and optimise rehabilitation outcomes

Phase I dose-escalation and pharmacokinetic study of a novel folate analogue AG2034

The novel folate analogue AG2034, which was designed as an inhibitor of GARFT (glycinamide ribonucleotide formyltransferase), was evaluated in this phase I study under the auspices of The Cancer Research Campaign, UK. AG2034 blocks de novo purine synthesis through inhibition of GARFT. A total of 28 patients with histologically proven intractable cancers were enrolled. AG2034 was administered as a short intravenous infusion once every 3 weeks. 8 dose levels ranging from 1–11 mg/m2 were evaluated with patients receiving up to 6 cycles. Dose-limiting toxicities in the form of mucositis, diarrhoea and vomiting were observed at doses of 6 mg/m2 and above. Significant levels of thrombocytopenia, neutropenia and anaemia were also recorded. Other sporadic toxicities included fatigue and myalgia. The MTD with this schedule of AG2034 was 5 mg/m2. Most side effects occurred more frequently with cumulative dosing. In keeping with this, pharmacokinetic analysis revealed evidence of drug accumulation. The AG2034 AUC0–24 increased by a median of 184% (range 20–389%) from cycle 1 to 3 in all 10 patients examined. No objective antitumour responses were observed in the study. © 2001 Cancer Research Campaign http://www.bjcancer.co

High-throughput eDNA monitoring of fungi to track functional recovery in ecological restoration

Fungi are key functional components of ecosystems (e.g. decomposers, symbionts), but are rarely included in restoration monitoring programs. Many fungi occur belowground, making them difficult to observe directly, but are observable with environmental DNA (eDNA) methods. Although eDNA approaches have been proposed as ecological monitoring tools for microbial diversity, their application to restoration projects is very limited. We used eDNA metabarcoding of fungal ITS barcodes on soil collected across a 10-year restoration chronosequence to explore fungal responses to restoration. We observed a dramatic shift in the fungal community towards that of the natural fungal community after just 10 years of active native plant revegetation. Agaricomycetes and other Basidiomycota – involved in wood decay and ectomycorrhizal symbiosis – increased in rarefied sequence abundance in older restored sites. Ascomycota dominated the fungal community, but decreased in rarefied sequence abundance across the restoration chronosequence. Our results highlight eDNA metabarcoding as a useful restoration monitoring tool that allows quantification of changes in important fungal indicator groups linked with functional recovery and, being underground, are normally omitted in restoration monitoring.DongFeng Yan, Jacob G. Mills, Nicholas J.C. Gellie, Andrew Bissett, Andrew J. Lowe, Martin F. Bree

Ability of matrix metalloproteinase-8 biosensor, IFMA, and ELISA immunoassays to differentiate between periodontal health, gingivitis, and periodontitis

Publisher Copyright: © 2022 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.Objective: The aim of this study was to determine the diagnostic utility of an MMP-8 biosensor assay in differentiating periodontal health from gingivitis and periodontitis and compare it with an established time-resolved immunofluorescence assay (IFMA) and enzyme-linked immunosorbent assay (ELISA). Background: Currently available antibody-based assays display a wide variability in their ability to accurately measure matrix metalloproteinase-8 (MMP-8) levels in saliva. Methods: Salivary MMP-8 levels were analyzed in 189 systemically healthy participants using an antibody-based biosensor prototype that operates using a surface acoustic wave technology and compared with IFMA and ELISA antibody assays. Participants were categorized into 3 groups: periodontal health (59), gingivitis (63), and periodontitis (67). A sub-population of participants (n = 20) with periodontitis received periodontal treatment and were monitored for 6 months. Results: All the assays demonstrated significantly higher salivary MMP-8 concentrations in participants with periodontitis versus gingivitis, periodontitis versus health, and gingivitis versus health (all p <.05). The biosensor data demonstrated significant correlations with IFMA (r =.354, p <.001) and ELISA (r =.681, p <.001). Significant reductions in salivary MMP-8 concentrations were detected by the biosensor (p =.030) and IFMA (p =.002) in participants with periodontitis 6 months after non-surgical periodontal treatment. IFMA had the best sensitivity (89.2%) for detecting periodontitis and gingivitis versus health and 96.6% for detecting periodontitis versus health and gingivitis. The biosensor had an AUC value of 0.81 and diagnostic accuracy of 74.2% for differentiating periodontitis and gingivitis from health; an AUC value of 0.86 and diagnostic accuracy of 82.8% for periodontitis versus health and gingivitis. Conclusions: The biosensor, IFMA, and ELISA assays differentiated between periodontal health, gingivitis, and periodontitis based on salivary MMP-8 levels. Only the biosensor and, particularly, IFMA identified an effect of periodontal treatment in the participants with periodontitis. Our findings support the potential utility of salivary oral fluid aMMP-8-based point-of-care technology in the future of periodontal diagnostics.Peer reviewe

Isolated Meningeal Recurrence of Transitional Cell Carcinoma of the Bladder

Meningeal carcinomatosis occurs in 1–18% of patients with solid tumours, most commonly carcinomas of the breast and lung or melanomas. There are relatively few reports of meningeal carcinomatosis in transitional cell carcinoma of the bladder. Isolated meningeal recurrence is particularly uncommon, and we present an unusual case of this in a 58-year-old man. The case was further complicated by the somewhat atypical presentation with a confirmed ischaemic stroke. The patient died one month after presentation

Relating psychiatric symptoms and self-regulation during the COVID-19 crisis

Disruptions of self-regulation are a hallmark of numerous psychiatric disorders. Here, we examine the relationship between transdiagnostic dimensions of psychopathology and changes in self-regulation in the early phase of the COVID-19 pandemic. We used a data-driven approach on a large number of cognitive tasks and self-reported surveys in training datasets. Then, we derived measures of self-regulation and psychiatric functioning in an independent population sample (N = 102) tested both before and after the onset of the COVID-19 pandemic, when the restrictions in place represented a threat to mental health and forced people to flexibly adjust to modifications of daily routines. We found independent relationships between transdiagnostic dimensions of psychopathology and longitudinal alterations in specific domains of self-regulation defined using a diffusion decision model. Compared to the period preceding the onset of the pandemic, a symptom dimension related to anxiety and depression was characterized by a more cautious behavior, indexed by the need to accumulate more evidence before making a decision. Instead, social withdrawal related to faster non-decision processes. Self-reported measures of self-regulation predicted variance in psychiatric symptoms both concurrently and prospectively, revealing the psychological dimensions relevant for separate transdiagnostic dimensions of psychiatry, but tasks did not. Taken together, our results are suggestive of potential cognitive vulnerabilities in the domain of self-regulation in people with underlying psychiatric difficulties in face of real-life stressors. More generally, they also suggest that the study of cognition needs to take into account the dynamic nature of real-world events as well as within-subject variability over time

Arbuscular mycorrhizal communities respond to nutrient enrichment and plant invasion in phosphorus‐limited eucalypt woodlands

Arbuscular mycorrhizal fungi (AMF) facilitate ecosystem functioning through provision of plant hosts with phosphorus (P), especially where soil P is limiting. Changes in soil nutrient regimes are expected to impact AMF, but the direction of the impact may depend on context. We predicted that nitrogen (N)-only enrichment promotes plant invasions and exacerbates their P limitation, increasing the utility of AMF and promoting AMF diversity. We expected that enrichment with N, P and other nutrients similarly promotes plant invasions, but decreases the benefit and diversity of AMF because P is readily available for both native and exotic plants. We tested these hypotheses in eucalypt woodlands of south-western Australia, that occur on soils naturally low in P. We evaluated AMF communities within three modified ground-layer states representing different types of nutrient enrichment and associated plant invasions. We compared these modified states to near-natural reference woodlands. AMF richness varied across ground-layer states. The moderately invaded/N-enriched state showed the highest AMF richness, while the highly invaded/NP-enriched state showed the lowest AMF richness. The reference state and the weakly invaded/enriched state were intermediate. AMF richness and colonisation were higher in roots of exotic than native plant species. AMF community composition differed among ground-layer states, with the highly invaded/NP-enriched state being most distinct. Distinctions among states were often driven by family-level patterns. Reference and moderately invaded/N-enriched states each supported distinct groups of zero-radius operational taxonomic units (zOTUs) in Acaulosporaceae, Gigasporaceae and Glomeraceae, whereas Gigasporaceae and Glomeraceae were nearly absent from the highly invaded/NP-enriched state. Further, Diversisporaceae and Glomeraceae were most diverse in the moderately invaded/N-enriched state. Synthesis. Both the nature of soil nutrient enrichment and plant provenance matter for AMF. N-only enrichment of low-P soils increased AMF richness, likely due to the introduction of AMF-dependent exotic plant species and exacerbation of their P limitation. In contrast, multi-nutrient enrichment, decreased AMF richness potentially due to a decrease in host dependence on AMF, regardless of host provenance. The changes in AMF community composition with nutrient enrichment and plant invasion warrant further research into predicting the functional implications of these changes

The Impact of Acceptance and Commitment Training and Multicultural Training on the stigmatizing attitudes and professional burnout of substance abuse counselors

Empirically validated methods for reducing stigma and prejudice toward recipients of behavioral healthcare services are badly needed. In the present study, two packages presented in one day workshops were compared to a biologically oriented Educational Control condition in the alleviation of stigmatizing attitudes in drug abuse counselors. One, Acceptance and Commitment Training (ACT), utilized acceptance, defusion, mindfulness, and values methods. The other, Multicultural Training, sensitized participants to group prejudices and biases. Measures of stigma and burnout were taken pre-training, post-training, and after a three month follow-up. Results showed that Multicultural Training had an impact on stigmatizing attitudes and burnout post-intervention but not at follow-up, but showed better gains in a sense of personal accomplishment as compared to the Educational Control at follow-up. ACT had a positive impact on stigma at follow-up and on burnout at post-treatment and follow-up and follow-up gains in burnout exceeded those of Multicultural Training. ACT also significantly changed the believability of stigmatizing attitudes. This process mediated the impact of ACT but not Multicultural Training on follow-up stigma and burnout. This preliminary study opens new avenues for reducing stigma and burnout in behavioral health counselors