Can Beach Cleans Do More Than Clean-Up Litter? Comparing Beach Cleans to Other Coastal Activities

Coastal visits not only provide psychological benefits but can also contribute to the accumulation of rubbish. Volunteer beach cleans help address this issue, but may only have limited, local impact. Consequently, it is important to study any broader benefits associated with beach cleans. This article examines the well-being and educational value of beach cleans, as well as their impacts on individuals’ behavioral intentions. We conducted an experimental study that allocated students (n = 90) to a beach cleaning, rock pooling, or walking activity. All three coastal activities were associated with positive mood and pro-environmental intentions. Beach cleaning and rock pooling were associated with higher marine awareness. The unique impacts of beach cleaning were that they were rated as most meaningful but linked to lower restorativeness ratings of the environment compared with the other activities. This research highlights the interplay between environment and activities, raising questions for future research on the complexities of person-environment interaction

A framework linking ecosystem services and human well‐being: Saltmarsh as a case study

1. The ecosystem services approach is based on the interdependencies between nature and human well‐being. However, while the ecosystem services aspect of this approach is well‐developed, the human well‐being aspect remains unstructured and vaguely defined. 2. An integrated conceptual framework was developed by adapting and linking the UK National Ecosystem Assessment‐Follow On framework with human well‐being domains. 3. As well as benefits, the notion of disbenefits was incorporated to recognise the potentially detrimental effects from interacting with nature. Benefits and disbenefits occur at the social–ecological interface and are classified by the seven domains of human well‐being they affect. 4. The framework is applied to saltmarsh habitat as a case study, highlighting knowledge gaps and the potential applicability and usefulness of the framework. In saltmarsh, benefits mainly accrue at larger scales with a greater impact affecting local to global individuals, while disbenefits tend to occur at a smaller scale and impact in‐situ individuals. 5. The framework provides in‐depth insight into links, trade‐offs and dichotomies between benefits and disbenefits and human well‐being, and improves accessibility to the complex research area of human well‐being. 6. This research can be a useful tool to guide environmental and health policy and management, as well as stakeholder engagement

Neuropathological characterisation of a novel TBK1 loss of function mutation associated with amyotrophic lateral sclerosis

Mutations in TANK binding kinase gene (TBK1) have been identified as causative in amyotrophic lateral sclerosis (ALS). Here, we examine the spectrum of TBK1 mutations in a cohort of ALS patients from Northern England, comparing missense and loss of function mutations with clinical phenotype. Analysis of 290 ALS cases identified seven variants, including one novel in-frame deletion (p.Ile85del). In silico analysis and review of the literature suggested that four variants, one nonsense mutation (p.Glu2Ter), two in-frame deletions (p.Ile85del, p.Glu643del) and one missense mutation (p.Gln565Pro) were pathogenic, whilst the remaining three missense mutations were variants of uncertain significance or benign. Post-mortem material was available from the patient with the novel in-frame deletion. Neuropathological examination established this individual had classical ALS pathology, with moderate phosphorylated TDP-43 neuronal and glial cytoplasmic inclusions in the motor cortex, skein-like inclusions in the lower motor neurons and “pre-inclusions” in the medulla. This corresponds to Type B FTLD-TDP pathology and is consistent with previously published literature on TBK1 mutants. In addition to demonstrating no changes in TBK1 staining, we are the first to show there was no differential expression of interferon regulatory factor IRF3, a downstream effector of TBK1 in the innate immunity pathway, in the TBK1-mutant tissue compared to controls. Comparison of clinical and neuropathological data, however, suggests that TBK1-ALS cases show classical ALS pathology but no specific phenotype

Multiscale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma

\ua9 2024 National Academy of Sciences. All rights reserved.Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this, we have created a multiscale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single-cell RNA sequencing, spatial global transcriptional profiling, and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retained signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN+ subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling. We propose that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community

Safety and Efficacy of Ombitasvir, Paritaprevir With Ritonavir ± Dasabuvir With or Without Ribavirin in Patients With Human Immunodeficiency Virus-1 and Hepatitis C Virus Genotype 1 or Genotype 4 Coinfection: TURQUOISE-I Part 2.

BACKGROUND: Ombitasvir, paritaprevir with ritonavir, and dasabuvir (OBV/PTV/r ± DSV) ±ribavirin (RBV) are approved to treat hepatitis C virus (HCV) genotype 1 and 4 infection. Here, we investigate the safety and efficacy of OBV/PTV/r + DSV ±RBV for HCV genotype 1, and OBV/PTV/r + RBV for HCV genotype 4, in human immunodeficiency virus (HIV)-1 coinfected patients with or without compensated cirrhosis. METHODS: TURQUOISE-I, Part 2 is a phase 3 multicenter study. Patients with or without cirrhosis were HCV treatment-naive or -experienced, on an HIV-1 antiretroviral regimen containing atazanavir, raltegravir, dolutegravir, or darunavir (for genotype 4 only), and had plasma HIV-1 ribonucleic acid <40 copies/mL at screening. Patients received OBV/PTV/r ± DSV ±RBV for 12 or 24 weeks. RESULTS: In total, 228 patients were treated according to guidelines. Sustained virologic response at posttreatment week 12 (SVR12) was achieved by 194 of 200 (97%) and 27 of 28 (96%) patients with HCV genotype 1 and genotype 4 infection, respectively. There were 2 virologic failures: 1 breakthrough and 1 relapse in a cirrhotic and a noncirrhotic patient with genotype 1b and 1a infection, respectively. One reinfection occurred at posttreatment week 12 in a genotype 1a-infected patient. Excluding nonvirologic failures, the SVR12 rates were 98% (genotype 1) and 100% (genotype 4). Adverse events were mostly mild in severity and did not lead to discontinuation. Laboratory abnormalities were rare. CONCLUSIONS: The OBV/PTV/r ±DSV was well tolerated and yielded high SVR12 rates in patients with HCV genotype 1 or genotype 4/HIV-1 coinfection. The OBV/PTV/r ± DSV ±RBV is a potent HCV treatment option for patients with HIV-1 coinfection, regardless of treatment experience

Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry

Hepatitis C virus (HCV) is one of the leading causes of liver diseases and transplantation worldwide. The current available therapy for HCV infection is based on interferon-α, ribavirin and the new direct-acting antivirals (DAAs), such as NS3 protease and NS5B polymerase inhibitors. However, the high costs of drug design, severe side effects and HCV resistance presented by the existing treatments demonstrate the need for developing more efficient anti-HCV agents. This study aimed to evaluate the antiviral effects of sorbifolin (1) and pedalitin (2), two flavonoids from Pterogyne nitens on the HCV replication cycle. These compounds were investigated for their anti-HCV activities using genotype 2a JFH-1 subgenomic replicons and infectious virus systems. Flavonoids 1 and 2 inhibited virus entry up to 45.0% and 78.7% respectively at non-cytotoxic concentrations. The mechanism of the flavonoid 2 block to virus entry was demonstrated to be by both the direct action on virus particles and the interference on the host cells. Alternatively, the flavonoid 1 activity was restricted to its virucidal effect. Additionally, no inhibitory effects on HCV replication and release were observed by treating cells with these flavonoids. These data are the first description of 1 and 2 possessing in vitro anti-HCV activity

Severe Acute Respiratory Infection-Preparedness: Protocol for a Multicenter Prospective Cohort Study of Viral Respiratory Infections

OBJECTIVES: Respiratory virus infections cause significant morbidity and mortality ranging from mild uncomplicated acute respiratory illness to severe complications, such as acute respiratory distress syndrome, multiple organ failure, and death during epidemics and pandemics. We present a protocol to systematically study patients with severe acute respiratory infection (SARI), including severe acute respiratory syndrome coronavirus 2, due to respiratory viral pathogens to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with clinical outcomes and severity. DESIGN: Prospective cohort study. SETTING: Multicenter cohort of patients admitted to an acute care ward or ICU from at least 15 hospitals representing diverse geographic regions across the United States. PATIENTS: Patients with SARI caused by infection with respiratory viruses that can cause outbreaks, epidemics, and pandemics. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements include patient demographics, signs, symptoms, and medications; microbiology, imaging, and associated tests; mechanical ventilation, hospital procedures, and other interventions; and clinical outcomes and hospital stress, with specimens collected on days 0, 3, and 7-14 after enrollment and at discharge. The primary outcome measure is the number of consecutive days alive and free of mechanical ventilation (VFD) in the first 30 days after hospital admission. Important secondary outcomes include organ failure-free days before acute kidney injury, shock, hepatic failure, disseminated intravascular coagulation, 28-day mortality, adaptive immunity, as well as immunologic and microbiologic outcomes. CONCLUSIONS: SARI-Preparedness is a multicenter study under the collaboration of the Society of Critical Care Medicine Discovery, Resilience Intelligence Network, and National Emerging Special Pathogen Training and Education Center, which seeks to improve understanding of prognostic factors associated with worse outcomes and increased resource utilization. This can lead to interventions to mitigate the clinical impact of respiratory virus infections associated with SARI