No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors ...associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.
The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.
2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 25·5% of 1965) and 1 year (232 28·9% of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 95% CI 0·46–0·99), obesity (0·50 0·34–0·74) and invasive mechanical ventilation (0·42 0·23–0·76). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 IQR 0·74–1·00), at 5 months (0·74 0·64–0·88) to 1 year (0·75 0·62–0·88), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters.
The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.
UK Research and Innovation and National Institute for Health Research.
Virulent Newcastle disease virus (NDV) was reported to cause rapid depletion of chicken bursa of Fabricius. Severe pathological condition of the organ is commonly associated with high levels of virus ...replication, intense inflammatory response and also the degree of apoptosis. In this study, the responses of chicken bursa of Fabricius infected with two different strains of velogenic NDV, namely AF2240 and IBS002, were investigated by observing cell population changes, oxidative stress, viral replication and cytokine expression in the organ. Subsequently, apoptosis of enriched bursal IgM+ cells was determined to help us elucidate possible host pathogen relationships between the chicken bursa of Fabricius and NDV infection.
The depletion of IgM+ cells and infiltration of macrophages were observed to be higher in bursa infected with AF2240 as compared to IBS002. In line with the increment of the macrophage population, higher nitric oxide (NO) and malondialdehyde (MDA) contents which indicated higher oxidative stress were also detected in bursa infected with NDV AF2240. In addition, higher pro-inflammatory cytokines and chemokine gene expression such as chicken CXCLi2, IL-18 and IFN-γ were observed in AF2240 infected bursa. Depletion of IgM+ cells was further confirmed with increased cell death and apoptosis of the cells in AF2240 infected bursa as compared to IBS002. However, it was found that the viral load for NDV strain IBS002 was comparatively higher than AF2240 although the magnitude of the pro- inflammatory cytokines expression and cell apoptosis was lower than AF2240.
The results of our study demonstrated that infection of NDV strains AF2240 and IBS002 caused apoptosis in bursa IgM+ cells and its severity was associated with increased expression of pro-inflammatory cytokines/chemokine, macrophage infiltration and oxidative stress as the infection duration was prolonged. However, of the two viruses, we observed that NDV AF2240 induced a greater magnitude of apoptosis in chicken bursa IgM+ cells in comparison to IBS002. This might be due to the high level of oxidative stress and inflammatory cytokines/chemokine as well as lower IL10 expression which subsequently led to a high rate of apoptosis in the chicken bursa of Fabricius although the detected viral load of AF2240 was lower than IBS002.
An open-label, multicenter, single-arm phase II trial was conducted to investigate the clinical activity of dacomitinib in recurrent/metastatic squamous-cell carcinoma of the head and neck ...(RM-SCCHN).
Eligible patients were administered dacomitinib at 45 mg orally daily, in 21-day cycles. Primary end point was objective response rate.
Sixty-nine patients were enrolled with a median age of 62 years. Among response-evaluable patients, 8 12.7%, 95% confidence interval (CI) 5.6% to 23.5% achieved a partial response and 36 (57.1%) had stable disease, lasting ≥24 weeks in 9 patients (14.3%). The median progression-free survival (PFS) was 12.1 weeks and the median overall survival (OS) was 34.6 weeks. Most adverse events (AEs) were tolerable. The most common grade 3 or higher treatment-related AEs were diarrhea (15.9%), acneiform dermatitis (8.7%), and fatigue (8.7%). Treatment-related AEs led to at least one dose interruption in 28 (40.6%) patients and dose reductions in 26 (37.7%). Permanent treatment discontinuation occurred in 8 (11.6%) patients due to treatment-related AEs.
Dacomitinib demonstrated clinical activity in RM-SCCHN, and the primary end point of this study was met. The toxicity profile of this agent was generally manageable with dose interruptions and adjustments.
Disposal of waste palm cooking oil (WPCO) via an environmental-friendly route is of major importance in the quest for sustainable development. In this study, WPCO was utilized instead of refined ...vegetable oils as the source of triglycerides for biodiesel production. WPCO contains several impurities, such as water and free fatty acids, which limit its application in catalytic transesterification processes. Consequently, a catalyst-free process using supercritical methanol was employed to investigate the potential of WPCO as an economical feedstock for biodiesel production. The parameters that influence the reaction, including reaction time, temperature and the molar ratio of alcohol to oil, were investigated. For comparison purposes, refined palm oil (RPO) was also subjected to supercritical methanol reaction and it was found that both processes produced comparable optimum yields of 80% at their respective optimum conditions. Hence, it can be concluded that WPCO has high potential as an economical and practical future source of biodiesel.
Existing evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in ...Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients.
Chemotherapy-receiving breast cancer patients (stages I–III) were recruited. Proinflammatory plasma cytokines concentrations interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte–macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder™) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain.
Ninety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1β was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1β and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022).
While elevated concentrations of IL-6 and IL-1β were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes.
Summary
Aims: Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate ...glycaemic control with sulphonylurea monotherapy.
Methods and patients: A total of 768 patients (18–77 years; HbA1c screening ≥ 7.5 to ≤ 10.0%) were randomised and treated with saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg vs. glyburide 10 mg for 24 weeks. Blinded uptitration glyburide was allowed in the glyburide‐only arm to a maximum total daily dose of 15 mg. Efficacy analyses were performed using ANCOVA and last‐observation‐carried‐forward methodology.
Results: At week 24, 92% of glyburide‐only patients were uptitrated to a total glyburide dose of 15 mg/day. Saxagliptin 2.5 and 5 mg provided statistically significant adjusted mean decreases from baseline to week 24 vs. uptitrated glyburide, respectively, in HbA1c (−0.54%, −0.64% vs. +0.08%; both p < 0.0001) and fasting plasma glucose (−7, −10 vs. +1 mg/dl; p = 0.0218 and p = 0.002). The proportion of patients achieving an HbA1c < 7% was greater for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide (22.4% and 22.8% vs. 9.1%; both p < 0.0001). Postprandial glucose area under the curve was reduced for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide (−4296 and −5000 vs. +1196 mg·min/dl; both p < 0.0001). Adverse event occurrence was similar across all groups. Reported hypoglycaemic events were not statistically significantly different for saxagliptin 2.5 (13.3%) and 5 mg (14.6%) vs. uptitrated glyburide (10.1%).
Conclusion: Saxagliptin added to submaximal glyburide therapy led to statistically significant improvements vs. uptitration of glyburide alone across key glycaemic parameters and was generally well tolerated.
Biodiversity assessment is constitutive in establishing conservation priorities and outcomes, and geodiversity complements species richness as a surrogate in the absence of species data, improves ...statistical modelling and can facilitate prediction of species distribution and abundance. Yet, geodiversity is frequently excluded, and biodiversity prioritised in conservation endeavours such as ecosystem-based management. Therefore, combined geodiversity and biodiversity assessment approaches present practical benefits to conservation such as improved collaboration between biologists and geoscientists, efficacious indicators of conservation value, and abatement of biodiversity partialities and wider inclusion of geodiversity in conservation literature. This study scientometrically analysed 240 biodiversity assessment publications to investigate geodiversity inclusiveness, methodological trends, geographic trends, environment-type trends and future directions in biodiversity assessment methods. Results showed these species richness articles frequently included geodiversity-relevant terms such as hydrological, soil, geological and geomorphological components, but the all-encompassing ‘geodiversity’ term was absent entirely. Geographic trends showed many potential economic, social, cultural and political factors influencing geodiversity inclusiveness in biodiversity assessment. For example, Australia’s relatively resource exploitative approach to geology and early involvement in the inception of the geodiversity concept could explain the high frequency of geological-related terms in Australian biodiversity assessments. Methodological trends showed dominance by field-based biodiversity assessments such as trapping methods, followed transects, quadrats, net methods and observations. Given the specific sample size of literature analysed, inferences from this study relate only to biodiversity assessment methods and not biodiversity discourse in its entirety. Subsequent research could investigate specific factors, such as social, economic or political, and their influence on geodiversity inclusiveness in biodiversity assessment methods.
A key task in the emerging field of bioelectronics is the transduction between ionic/protonic and electronic signals at high fidelity. This is a considerable challenge since the two carrier types ...exhibit intrinsically different physics and are best supported by very different materials typeselectronic signals in inorganic semiconductors and ionic/protonic signals in organic or bio-organic polymers, gels, or electrolytes. Here we demonstrate a new class of organic–inorganic transducing interface featuring semiconducting nanowires electrostatically gated using a solid proton-transporting hygroscopic polymer. This model platform allows us to study the basic transducing mechanisms as well as deliver high fidelity signal conversion by tapping into and drawing together the best candidates from traditionally disparate realms of electronic materials research. By combining complementary n- and p-type transducers we demonstrate functional logic with significant potential for scaling toward high-density integrated bioelectronic circuitry.
The combination of a geometrically frustrated lattice, and similar energy scales between degrees of freedom endows two-dimensional Kagome metals with a rich array of quantum phases and renders them ...ideal for studying strong electron correlations and band topology. The Kagome metal, FeGe is a noted example of this, exhibiting A-type collinear antiferromagnetic (AFM) order at T
≈ 400 K, then establishes a charge density wave (CDW) phase coupled with AFM ordered moment below T
≈ 110 K, and finally forms a c-axis double cone AFM structure around T
≈ 60 K. Here we use neutron scattering to demonstrate the presence of gapless incommensurate spin excitations associated with the double cone AFM structure of FeGe at temperatures well above T
and T
that merge into gapped commensurate spin waves from the A-type AFM order. Commensurate spin waves follow the Bose factor and fit the Heisenberg Hamiltonian, while the incommensurate spin excitations, emerging below T
where AFM order is commensurate, start to deviate from the Bose factor around T
, and peaks at T
. This is consistent with a critical scattering of a second order magnetic phase transition with decreasing temperature. By comparing these results with density functional theory calculations, we conclude that the incommensurate magnetic structure arises from the nested Fermi surfaces of itinerant electrons and the formation of a spin density wave order.
PDF
