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viron Assess Manag 2022;001-11. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).Pharmaceutical companies regularly need to make decisions about drug development programs based on the limited knowledge from early stage clinical trials. In this situation, eliciting the judgements of experts is an attractive approach for synthesising evidence on the unknown quantities of interest. When calculating the probability of success for a drug development program, multiple quantities of interest-such as the effect of a drug on different endpoints-should not be treated as unrelated. We discuss two approaches for establishing a multivariate distribution for several related quantities within the SHeffield ELicitation Framework (SHELF). The first approach elicits experts' judgements about a quantity of interest conditional on knowledge about another one. For the second approach, we first elicit marginal distributions for each quantity of interest. Then, for each pair of quantities, we elicit the concordance probability that both lie on the same side of their respective elicited medians. This allows us to specify a copula to obtain the joint distribution of the quantities of interest. We show how these approaches were used in an elicitation workshop that was performed to assess the probability of success of the registrational program of an asthma drug. The judgements of the experts, which were obtained prior to completion of the pivotal studies, were well aligned with the final trial results.Subacute sclerotic panencephalitis (SSPE) is a refractory neurological disorder after exposure to measles virus. Recently, SSPE cases have been treated with antiviral therapies, but data on the efficacy are inconclusive. Abnormal tau accumulation has been reported in the brain tissue of SSPE cases, but there are few reports in which this is amply discussed. Five autopsied cases diagnosed as definite SSPE were included in this study. The subject age or disease duration ranged from 7.6 to 40.9 years old or from 0.5 to 20.8 years, respectively. Cases 3 and 4 had been treated with antiviral therapies. All evaluated cases showed marked brain atrophy with cerebral ventricle dilatation; additionally, marked demyelination with fibrillary gliosis were observed in the cerebral white matter. The brainstem, cerebellum, and spinal cord were relatively preserved. Immunoreactivity (IR) against measles virus was seen in the brainstem tegmentum, neocortex, and/or limbic cortex of the untreated cases but was rarely seen in the two treated cases. Activated microglia were broadly observed from the cerebrum to the spinal cord and had no meaningful difference among cases. Neurofibrillary tangles characterized by a combination of 3- and 4-repeat tau were observed mainly in the oculomotor nuclei, locus coeruleus, and limbic cortex. IR against phosphorylated tau was seen mainly in the cingulate gyrus, oculomotor nuclei, and pontine tegmentum, and tended to be observed frequently in cases with long disease durations but also tended to decrease along with neuronal loss, as in Case 5, which had the longest disease duration. Since the distribution of phosphorylated tau was independent from that of measles virus, the tauopathy following SSPE was inferred to be the result of diffuse brain inflammation triggered by measles rather than a direct result of measles virus. Moreover, antiviral therapies seemed to suppress measles virus but not the progression of tauopathy.

Face mask use has become widespread as a means of reducing transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Research suggests face coverings can impact speech discrimination, therapeutic alliance and the interpretation of non-verbal cues. HDAC inhibitor mechanism However, there is little research into the impact of face masks on people with communication difficulties (pwCD) post-stroke.

To explore the perspectives of service users and staff on a stroke rehabilitation unit in order to understand the impact of staff wearing face masks on the experience of rehabilitation for pwCD. Strategies that might improve the experience of rehabilitation for pwCD were also explored.

Semi-structured interviews and a focus group were conducted with six pwCD and five health professionals (HPs) on a stroke rehabilitation unit. The data were analysed using reflexive thematic analysis.

Four main interacting themes were identified from the data (1) face masks as a barrier to effective communication; (2) face masks as aelpful for clinicians to have a discussion with pwCD post-stroke to understand the impact of face mask use on them personally and what strategies they would find most helpful within rehabilitation. Additional training by speech and language therapists on supporting effective communication and successful interaction with pwCD may be indicated in the context of face mask use.Thrombospondin-1 (TSP-1) is a key mediator of renal ischemia-reperfusion injury (IRI), a major cause of kidney dysfunction under various disease conditions and a risk factor of renal allograft rejection. In this study, we developed a nanotechnology-based therapy targeting TSP-1 to prevent renal IRI. A biocompatible nanoparticle (NP) capable of specific binding to TSP-1 was prepared by conjugating NPs with TSP-1-binding (LSKL) peptides. LSKL/NPs not only effectively adsorbed recombinant TSP-1 proteins in vitro, but also efficiently neutralized TSP-1 in mice undergoing renal IRI. IRI-induced elevation of TSP-1 in the kidney was significantly inhibited by post-IR treatment with LSKL/NPs, but not free LSKL or NPs. Furthermore, TSP-1 proteins adsorbed on LSKL/NPs were functionally inactive and unable to induce apoptosis in renal tubular epithelial cells. Importantly, LSKL/NPs induced strong protection against renal IRI, as shown by markedly diminished serum creatinine levels and improved histological lesions of the kidney. Thus, LSKL/NPs provide a useful means of depleting and inactivating TSP-1 and a potential therapy for renal IRI.

Collagenase, hyaluronidase, elastase, and tyrosinase enzymes are overexpressed and overactive in the skin aging process and hydrolyze the components of the dermal extracellular matrix (ECM) of the skin; these enzymes produce the clinical framework of aging, which includes skin dryness, hyperpigmentation, wrinkles, and inelasticity.

The aim of this study was to explore the potential use of waste from two Argentine native fruits, namely Ziziphus mistol, and red and orange varieties of Solanum betaceum, as sources of bioactive compounds.

Phenolic enriched extracts (PEE) from waste of Z.mistol and S.betaceum were obtained, and their total contents of phenolics and flavonoids were evaluated. The bioactive properties of the extracts were analyzed by measuring their antioxidant capacity and the inhibitory activity on collagenase, hyaluronidase, elastase, and tyrosinase enzymes.

The increased ability to inhibit the collagenase was demonstrated by the PEE of Z.mistol seeds and peel, while the enzyme elastase was mostly inhibited by extracts of S.betaceum skin. Z.mistol seed extract was the most active to inhibit hyaluronidase, reaching 96% inhibition at a concentration of 100μg GAE/mL. The most active extracts to inhibit the tyrosinase enzyme were obtained from the peel of two varieties of chilto fruits, orange and red, and the mistol seed.

The results obtained suggest that Z.mistol and S.betaceum waste may be considered as a source of bioactive phenolics. Here, Argentine native fruits waste is presented as a most promising alternative in cosmetic products, with future uses such as hydrogels, creams, or lotions.

The results obtained suggest that Z. mistol and S. betaceum waste may be considered as a source of bioactive phenolics. Here, Argentine native fruits waste is presented as a most promising alternative in cosmetic products, with future uses such as hydrogels, creams, or lotions.Tacrolimus (TAC) is a dose-dependent immunosuppressor with considerable intrapatient variability (IPV) in its pharmacokinetics. The aim of this work is to ascertain the association between TAC IPV at 6 months after liver transplantation (LT) and patient outcome. This single-center cohort study retrospectively analyzed adult patients who underwent transplantation from 2015 to 2019 who survived the first 6 months with a functioning graft. The primary end point was the patient's probability of death and the secondary outcome was the loss of renal function between month 6 and the last follow-up. TAC IPV was estimated by calculating the coefficient of variation (CV) of the dose-corrected concentration (C0 /D) between the third and sixth months post-LT. Of the 140 patients who underwent LT included in the study, the low-variability group (C0 /D CV  less then  27%) comprised 105 patients and the high-variability group (C0 /D CV ≥ 27%) 35 patients. One-, 3-, and 5-year patient survival rates were 100%, 82%, and 72% in the high-variability group versus 100%, 97%, and 93% in the low-variability group, respectively (p = 0.005). Moreover, significant impaired renal function was observed in the high-variability group at 1 year (69 ± 16 ml/min/1.73 m2 vs. 78 ± 16 ml/min/1.73 m2 , p = 0.004) and at 2 years post-LT (69 ± 17 ml/min/1.73 m2 vs. 77 ± 15 ml/min/1.73 m2 , p = 0.03). High C0 /D CV 3-6 months remained independently associated with worse survival (hazard ratio = 3.57, 95% CI = 1.32-9.67, p = 0.012) and loss of renal function (odds ratio = 3.47, 95% CI = 1.30-9.20, p = 0.01). Therefore, high IPV between the third and sixth months appears to be an early and independent predictor of patients with poorer liver transplant outcomes.This study examined the relationship between the personal predisposing factors of patients and the severity of pressure injuries (PIs) developed during surgery. This retrospective cohort study collected 439 cases of peri-operative PIs. Using binary logistic regression to identify the variables associated with PI severity, the effects of interactions between associated variables were then tested. The results of this study revealed that among the personal predisposing factors, only higher patient age (P = .001) and higher body mass index (P  less then  .001) posed a greater risk of stage 2 PIs or higher. Among the surgery-related facilitating factors, only patients who were placed in the prone position during surgery and patients who lost ≥1000 mL of blood during surgery were at greater risk of stage 2 PIs or higher, compared, respectively, to those placed in the supine position and those who lost ≤100 mL of blood. Furthermore, the amount of blood lost during surgery moderated the influence of age on PI severity. For elderly patients who are expected to lose a large blood volume during surgery or lose an immeasurable amount of blood due to the use of cardiopulmonary bypass, taking more precautionary measures to prevent PIs is recommended.Few researches have focused on the role of nanoscale zero-valent iron (nZVI) in Fenton-like process for polycyclic aromatic hydrocarbons (PAHs) removal. In this study, the naphthalene (NAP) degradation tests in ultrapure water showed that nZVI addition could enhance NAP degradation from 79.7% to 99.0% in hydrogen peroxide (H2 O2 )/Fe (II)/nZVI/NAP system at the molar ratio of 10/5/3/1, showing the excellent role of nZVI in promoting NAP removal. Multiple linear regression analysis found that the correlation coefficient between H2 O2 consumption and NAP degradation was converted from -9.17 to 0.48 with nZVI and 1-mM H2 O2 , indicating that nZVI could decompose H2 O2 more beneficially for NAP degradation. Multiple Fe (II)-dosing and iron leaching tests revealed that nZVI could gently liberate Fe (II) and promote Fe (II)/Fe (III) redox cycle to enhance the NAP degradation. When the H2 O2 /Fe (II)/nZVI/NAP molar ratios of 10/5/3/1 and 50/25/15/1 were applied in the simulated NAP contaminated actual groundwater and soil slurry, respectively, 75.