Search

Microplastics (MP) are vectors for other environmental contaminants, such as metals, being a considerable problem, especially in the aquatic ecosystem. To investigate the combined effects of MP (high density polyethylene) with lead (Pb), we exposed the mangrove fiddler crab Minuca vocator to Pb (50 mg L -1 ), and MP (25 mg L -1 ) alone and in mixture, for 5 days. We aimed to determine Pb and MP bioaccumulation, as well as physiological (oxygen consumption and hemolymph osmolality) and biochemical (superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation) traits effects. Co-exposure of MP and Pb significantly increased the bioaccumulation of Pb, but reduced MP tissue accumulation. Regarding the physiological traits, increasing osmolality and oxygen consumption rates compared to the control were observed, particularly in the combined Pb and MP exposure. As to biochemical traits, the combination of Pb and MP induced the most significant responses in the enzymatic profile antioxidant enzyme activity. The catalase (CAT), glutathione peroxidase (GPx), and dismutase superoxide (SOD) decreased compared to individual exposure effects; the combination of MP and Pb had a synergistic effect on promoting lipid peroxidation (LPO). The co-exposure of MP and Pb acted synergistically when compared to the effects of the isolated compounds. Due to the increasing MP contamination in mangroves, more severe physiological and biochemical effects can be expected on mangrove crabs exposed to metal contamination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Enrolling patients with metastatic urothelial carcinoma (mUC) in phase I trials provides an opportunity to identify biological drug activity. Developing prognostic scores may aid in patient selection for phase 1 trials., Patients and Methods: We analyzed records of patients with mUC who participated in targeted therapy and immunotherapy phase I clinical trials at MD Anderson Cancer Center (MDACC). The Bellmunt and Bajorin scores were calculated as bladder cancer-specific prognostic scores. The Royal Marsden Hospital (RMH) and MDACC scores were calculated as phase I prognostic scores. Hazard ratios (HR) were calculated using the Cox proportional hazard model. The prognostic value of the Bellmunt, Bajorin, RMH, and MDACC scores were assessed using the Likelihood ratio (LR) χ2 test and the c-index., Results: Between 2015 and 2019, 43 patients were enrolled in phase I trials and 12 were enrolled in >I trial leading to a total of 57 trial participants (TPs). Ninty-seven percent of TPs received prior platinum therapy and 60% received a prior checkpoint inhibitor. Median overall survival (OS) and progression-free survival (PFS) were significantly shorter with increasing Bajorin, RMH, or MDACC scores, but not with increasing Bellmunt score. The RMH (c-index=0.658, LR χ2=11.8, P=.008) and MDACC scores (c-index =0.66, LR χ2=12.76, P=.01) outperformed the Bajorin score (c-index=0.522, LR χ2=1.22, P=.5) and the Bellmunt score (c-index=0.537, LR χ2=0.36, P=.9) in predicting overall survivalover. The Bajorin, RMH, and MDACC scores, but not the Bellmunt score, were also predictive of progression-free survival (PFS)prog. The RMH and MDACC scores again outperformed the Bajorin scoreand the Bellmunt score for predicting PFS., Conclusion: The RMH and MDACC phase I prognostic scores accurately predicted survival in patients with mUC and outperformed the bladder cancer-specific scores at time of enrollment on phase 1 clinical trials. The RMH and MDACC scores could optimize selection of patients with mUC for phase I clinical trials., (Copyright © 2021. Published by Elsevier Inc.)

HIV-1 protease is an essential therapeutic target for the design and development of antiviral inhibitors to treat AIDS. We used room temperature neutron crystallography to accurately determine hydrogen atom positions in several protease complexes with clinical drugs, amprenavir and darunavir. Hydrogen bonding interactions were carefully mapped to provide an unprecedented picture of drug binding to the protease target. We demonstrate that hydrogen atom positions within the enzyme catalytic site can be altered by introducing drug resistant mutations and by protonating surface residues that trigger proton transfer reactions between the catalytic Asp residues and the hydroxyl group of darunavir. When protein perdeuteration is not feasible, we validate the use of initial H/D exchange with unfolded protein and partial deuteration in pure D 2 O with hydrogenous glycerol to maximize deuterium incorporation into the protein, with no detrimental effects on the growth of quality crystals suitable for neutron diffraction experiments., (© 2020 Elsevier Inc. All rights reserved.)

Background: Stuttering and word-finding difficulty (WFD) are two types of communication difficulty that occur frequently in children who learn English as an additional language (EAL), as well as those who only speak English. The two disorders require different, specific forms of intervention. Prior research has described the symptoms of each type of difficulty. This paper describes the development of a non-word repetition test (UNWR), applicable across languages, that was validated by comparing groups of children identified by their speech and language symptoms as having either stuttering or WFD., Aims: To evaluate whether non-word repetition scores using the UNWR test distinguished between children who stutter and those who have a WFD, irrespective of the children's first language., Methods & Procedures: UNWR was administered to ninety-six 4-5-year-old children attending UK schools (20.83% of whom had EAL). The children's speech samples in English were assessed for symptoms of stuttering and WFD. UNWR scores were calculated., Outcomes & Results: Regression models were fitted to establish whether language group (English only/EAL) and symptoms of (1) stuttering and (2) WFD predicted UNWR scores. Stuttering symptoms predicted UNWR, whereas WFD did not. These two findings suggest that UNWR scores dissociate stuttering from WFD. There were no differences between monolingual English-speakers and children who had EAL., Conclusions & Implications: UNWR scores distinguish between stuttering and WFD irrespective of language(s) spoken, allowing future evaluation of a range of languages in clinics or schools., (© 2016 Royal College of Speech and Language Therapists.)