Enhancing Human Health and Wellbeing through Sustainably and Equitably Unlocking a Healthy Ocean's Potential.

A healthy ocean is essential for human health, and yet the links between the ocean and human health are often overlooked. By providing new medicines, technologies, energy, foods, recreation, and inspiration, the ocean has the potential to enhance human health and wellbeing. However, climate change, pollution, biodiversity loss, and inequity threaten both ocean and human health. Sustainable realisation of the ocean's health benefits will require overcoming these challenges through equitable partnerships, enforcement of laws and treaties, robust monitoring, and use of metrics that assess both the ocean's natural capital and human wellbeing. Achieving this will require an explicit focus on human rights, equity, sustainability, and social justice. In addition to highlighting the potential unique role of the healthcare sector, we offer science-based recommendations to protect both ocean health and human health, and we highlight the unique potential of the healthcare sector tolead this effort.

Somatic polyploidy supports biosynthesis and tissue function by increasing transcriptional output.

Cell size and biosynthetic capacity generally increase with increased DNA content. Polyploidy has therefore been proposed to be an adaptive strategy to increase cell size in specialized tissues with high biosynthetic demands. However, if and how DNA concentration limits cellular biosynthesis in vivo is not well understood, and the impacts of polyploidy in non-disease states is not well studied. Here, we show that polyploidy in the C. elegans intestine is critical for cell growth and yolk biosynthesis, a central role of this organ. Artificially lowering the DNA/cytoplasm ratio by reducing polyploidization in the intestine gave rise to smaller cells with more dilute mRNA. Highly-expressed transcripts were more sensitive to this mRNA dilution, whereas lowly-expressed genes were partially compensated - in part by loading more RNA Polymerase II on the remaining genomes. DNA-dilute cells had normal total protein concentration, which we propose is achieved by increasing production of translational machinery at the expense of specialized, cell-type specific proteins.

COVID-19 Immunologic Antiviral Therapy With Omalizumab (CIAO)-a Randomized Controlled Clinical Trial.

Background: Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties. Objective: We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for coronavirus disease 2019 (COVID-19) pneumonia. Methods: This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization. Results: Of 41 patients recruited, 40 were randomized (20 received the study drug and 20 placebo). The median age of the patients was 74 years and 55.0% were male. Omalizumab was associated with a 92.6% posterior probability of a reduction in mechanical ventilation and death on day 14 with an adjusted odds ratio of 0.11 (95% credible interval 0.002-2.05). Omalizumab was also associated with a 75.9% posterior probability of reduced all-cause mortality on day 28 with an adjusted odds ratio of 0.49 (95% credible interval, 0.06-3.90). No statistically significant differences were found for the time to clinical improvement and duration of hospitalization. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events. Conclusions: These results suggest that omalizumab could prove protective against death and mechanical ventilation in hospitalized patients with COVID-19. This study could also support the development of a phase III trial program investigating the antiviral and anti-inflammatory effect of omalizumab for severe respiratory viral illnesses requiring hospital admission. ClinicalTrials.gov ID: NCT04720612.

Valuing the health benefits of nature-based recreational physical activity in England.

Physical activity (PA) reduces the risk of several non-communicable diseases (NCDs). Natural environments support recreational PA. Using data including a representative cross-sectional survey of the English population, we estimated the annual value of nature-based PA conducted in England in 2019 in terms of avoided healthcare and societal costs of disease. Population-representative data from the Monitor of Engagement with the Natural Environment (MENE) survey (n = 47,580; representing 44,386,756) were used to estimate the weekly volume of nature-based recreational PA by adults in England in 2019. We used epidemiological dose-response data to calculate incident cases of six NCDs (ischaemic heart disease (IHD), ischaemic stroke (IS), type 2 diabetes (T2D), colon cancer (CC), breast cancer (BC) and major depressive disorder (MDD)) prevented through nature-based PA, and estimated associated savings using published costs of healthcare, informal care and productivity losses. We investigated additional savings resulting from hypothetical increases in: (a) visitor PA and (b) visitor numbers. In 2019, 22million adults > 16 years of age in England visited natural environments at least weekly. At reported volumes of nature-based PA, we estimated that 550 cases of IHD, 168 cases of IS, 1,410 cases of T2D, 41 cases of CC, 37 cases of BC and 10,552 cases of MDD were prevented, creating annual savings of £108.7million (95 % uncertainty interval: £70.3million; £150.3million). Nature-based recreational PA in England results in reduced burden of disease and considerable annual savings through prevention of priority NCDs. Strategies that increase nature-based PA could lead to further reductions in the societal burden of NCDs.

Accelerator mass spectrometry measurements of 233U in groundwater, soil and vegetation at a legacy radioactive waste site.

Low-level radioactive wastes were disposed at the Little Forest Legacy Site (LFLS) near Sydney, Australia between 1960 and 1968. According to the disposal records, 233U contributes a significant portion of the inventory of actinide activity buried in the LFLS trenches. Although the presence of 233U in environmental samples from LFLS has been previously inferred from alpha-spectrometry measurements, it has been difficult to quantify because the 233U and 234U α-peaks are superimposed. Therefore, the amounts of 233U in groundwaters, soils and vegetation from the vicinity of the LFLS were measured using accelerator mass spectrometry (AMS). The AMS results show the presence of 233U in numerous environmental samples, particularly those obtained within, and in the immediate vicinity of, the trenched area. There is evidence for dispersion of 233U in groundwater (possibly mobilised by co-disposed organic liquids), and the data also suggest other sources of 233U contamination in addition to the trench wastes. These may include leakages and spills from waste drums as well as waste burnings, which also occurred at the site. The AMS results confirm the historic information regarding disposal of 233U in the LFLS trenches. The AMS technique has been valuable to ascertain the distribution and environmental behaviour of 233U at the LFLS and the results demonstrate the applicability of AMS for evaluating contamination of 233U at other radioactive waste sites.

The use of Enhanced Vegetation Index for assessing access to different types of green space in epidemiological studies.

BACKGROUND: Exposure to green space can protect against poor health through a variety of mechanisms. However, there is heterogeneity in methodological approaches to exposure assessments which makes creating effective policy recommendations challenging. OBJECTIVE: Critically evaluate the use of a satellite-derived exposure metric, the Enhanced Vegetation Index (EVI), for assessing access to different types of green space in epidemiological studies. METHODS: We used Landsat 5-8 (30 m resolution) to calculate average EVI for a 300 m radius surrounding 1.4 million households in Wales, UK for 2018. We calculated two additional measures using topographic vector data to represent access to green spaces within 300 m of household locations. The two topographic vector-based measures were total green space area stratified by type and average private garden size. We used linear regression models to test whether EVI could discriminate between publicly accessible and private green space and Pearson correlation to test associations between EVI and green space types. RESULTS: Mean EVI for a 300 m radius surrounding households in Wales was 0.28 (IQR = 0.12). Total green space area and average private garden size were significantly positively associated with corresponding EVI measures (ß = < 0.0001, 95% CI: 0.0000, 0.0000; ß = 0.0001, 95% CI: 0.0001, 0.0001 respectively). In urban areas, as average garden size increases by 1 m2, EVI increases by 0.0002. Therefore, in urban areas, to see a 0.1 unit increase in EVI index score, garden size would need to increase by 500 m2. The very small ß values represent no 'measurable real-world' associations. When stratified by type, we observed no strong associations between greenspace and EVI. IMPACT: It is a widely implemented assumption in epidiological studies that an increase in EVI is equivalent to an increase in greenness and/or green space. We used linear regression models to test associations between EVI and potential sources of green reflectance at a neighbourhood level using satellite imagery from 2018. We compared EVI measures with a 'gold standard' vector-based dataset that defines publicly accessible and private green spaces. We found that EVI should be interpreted with care as a greater EVI score does not necessarily mean greater access to publicly available green spaces in the hyperlocal environment.

Mechanisms underlying the associations between different types of nature exposure and sleep duration: An 18-country analysis.

Whilst green space has been linked to healthier sleep outcomes, the roles of specific types of nature exposure, potential underlying mechanisms, and between-country variations in nature-sleep associations have received little attention. Drawing on cross-sectional survey data from an 18-country sample of adults (N = 16,077) the current study examined: 1) the relative associations between six different types of nature exposure (streetscape greenery, blue view from home, green space within 1 km, coast within 1 km, green space visits, blue space visits) and insufficient sleep (<6 h vs. 7-10 h per day); 2) whether these relationships were mediated by better mental wellbeing and/or physical activity; and 3) the consistency of these pathways among the different countries. After controlling for covariates, neighbourhood nature measures (green space, coast within 1 km) were not significantly associated with insufficient sleep; but nature visible from home (streetscape greenery, blue views) and recreational visits to green and blue spaces were each associated with less insufficient sleep. Significant nature-sleep associations were mediated, to varying degrees, by better mental wellbeing, but not self-reported physical activity. Country-level heterogeneity in the strength of nature-sleep associations was observed. Increasing nature visible from the home may represent a promising strategy for promoting healthier sleep duration at the population level, whilst nature-based interventions encouraging individuals to spend time in local green/blue spaces may be an appropriate target to assist individuals affected by insufficient sleep.

Associations of nature contact with emotional ill-being and well-being: the role of emotion regulation.

Nature contact has associations with emotional ill-being and well-being. However, the mechanisms underlying these associations are not fully understood. We hypothesised that increased adaptive and decreased maladaptive emotion regulation strategies would be a pathway linking nature contact to ill-being and well-being. Using data from a survey of 600 U.S.-based adults administered online in 2022, we conducted structural equation modelling to test our hypotheses. We found that (1) frequency of nature contact was significantly associated with lesser emotional ill-being and greater emotional well-being, (2) effective emotion regulation was significantly associated with lesser emotional ill-being and greater emotional well-being, and (3) the associations of higher frequency of nature contact with these benefits were partly explained via emotion regulation. Moreover, we found a nonlinear relationship for the associations of duration of nature contact with some outcomes, with a rise in benefits up to certain amounts of time, and a levelling off after these points. These findings support and extend previous work that demonstrates that the associations of nature contact with emotional ill-being and well-being may be partly explained by changes in emotion regulation.

Nature visits, but not residential greenness, are associated with reduced income-related inequalities in subjective well-being.

Nature exposure can promote human health and well-being. Additionally, there is some, albeit mixed, evidence that this relationship is stronger for socio-economically disadvantaged groups (equigenesis). Using a cross-sectional survey of the Austrian population (N = 2300), we explored the relationships between both residential greenness and recreational nature visits, and affective (WHO-5 Well-Being Index) and evaluative (Personal Well-Being Index-7) subjective well-being. Partially supporting the equigenesis hypothesis, regression analyses controlling for potential confounders found that recreational visit frequency, but not residential greenness, moderated the effect of income-related disparities in both subjective well-being metrics. Results suggest that merely making neighborhoods greener may not itself help reduce inequalities in subjective well-being. Additionally, greater efforts are also needed to support individuals from all sectors of society to access natural settings for recreation as this could significantly improve the well-being of some of the poorest in society.

Exploring public risk perceptions of microplastics: Findings from a cross-national qualitative interview study among German and Italian citizens.

Microplastics are receiving growing attention in the public debate, while the scientific assessment of risks of microplastics to ecological and human health is still ongoing. Previous studies suggest concerns among the general public with country-specific differences. However, little is known about the reasoning underlying these concerns. By conducting qualitative interviews with German (n = 15) and Italian citizens (n = 15), this study adopted a cross-national perspective to investigate which concepts shape citizens' perceptions of microplastics. A qualitative content analysis was used, with coding categories and subcategories developed inductively. Results showed that interviewees formed assumptions around microplastics despite own uncertainties, transferred knowledge from macro- to microplastics, and used the concepts of accumulation and dose-response relationship to make sense of the topic. Moreover, they saw the domains of human health and the environment as intertwined and expressed helplessness when discussing solutions to the microplastics issue. Many themes on the topic were similar in both samples, but there were also some differences. For instance, whereas Italian participants talked about marine-related microplastics, German participants talked about airborne sources; also, German participants tended to recognize more strongly the actions their country was putting in place to address the problem. These findings underscore the need for proactive risk communication despite remaining gaps in scientific risk assessment. Beyond providing technical information, communicators should consider the reasoning behind risk perception on microplastics and address scientific uncertainty as well as the interconnectedness between the domains of human health and the environment.

Papillary Hemangioma Harbors Somatic GNA11 and GNAQ Mutations.

Papillary hemangioma (PH) is a small, primarily dermal lesion occurring predominantly in the head and neck in both children and adults. Its signature characteristics are dilated thin-walled channels containing papillary clusters of mainly capillary-sized vessels and endothelial cytoplasmic eosinophilic inclusions. Given certain histopathologic similarities to congenital hemangioma which harbor mutations in GNAQ and GNA11 , we investigated whether similar mutations are present in PH. Seven PH specimens were studied. All presented in the first 4 years of life, with one being noted at birth. With the exception of one lesion, all were in the head and neck. Lesions were bluish and ranged in size from 0.5 to 2.8 cm. Four samples had GNA11 p.Q209L and 3 had GNAQ p.Q209L missense mutations. Mutations in GNA11 and GNAQ are associated with other types of somatic vascular lesions including capillary malformation, congenital hemangioma, anastomosing hemangioma, thrombotic anastomosing hemangioma, and hepatic small cell neoplasm. Shared mutations in GNA11 and GNAQ may account for some overlapping clinical and pathologic features in these entities, perhaps explicable by the timing of the mutation or influence of the germline phenotype.

The economics of nature's healing touch: A systematic review and conceptual framework of green space, pharmaceutical prescriptions, and healthcare expenditure associations.

Green spaces play a crucial role in promoting sustainable and healthy lives. Recent evidence shows that green space also may reduce the need for healthcare, prescription medications, and associated costs. This systematic review provides the first comprehensive assessment of the available literature examining green space exposure and its associations with healthcare prescriptions and expenditures. We applied Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to search MEDLINE, Scopus, and Web of Science for observational studies published in English through May 6, 2023. A quality assessment of the included studies was conducted using the Office of Health Assessment and Translation (OHAT) tool, and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessment was used to evaluate the overall quality of evidence. Our search retrieved 26 studies that met the inclusion criteria and were included in our review. Among these, 20 studies (77 % of the total) showed beneficial associations of green space exposure with healthcare prescriptions or expenditures. However, most studies had risks of bias, and the overall strength of evidence for both outcomes was limited. Based on our findings and related bodies of literature, we present a conceptual framework to explain the possible associations and complex mechanisms underlying green space and healthcare outcomes. The framework differs from existing green space and health models by including upstream factors related to healthcare access (i.e., rurality and socioeconomic status), which may flip the direction of associations. Additional research with lower risks of bias is necessary to validate this framework and better understand the potential for green space to reduce healthcare prescriptions and expenditures.

Seasonality as a driver of pH1N12009 influenza vaccination campaign impact.

Although the most recent respiratory virus pandemic was triggered by a Coronavirus, sustained and elevated prevalence of highly pathogenic avian influenza viruses able to infect mammalian hosts highlight the continued threat of pandemics of influenza A virus (IAV) to global health. Retrospective analysis of pandemic outcomes, including comparative investigation of intervention efficacy in different regions, provide important contributions to the evidence base for future pandemic planning. The swine-origin IAV pandemic of 2009 exhibited regional variation in onset, infection dynamics and annual infection attack rates (IARs). For example, the UK experienced three severe peaks of infection over two influenza seasons, whilst Australia experienced a single severe wave. We adopt a seasonally forced 2-subtype model for the transmission of pH1N12009 and seasonal H3N2 to examine the role vaccination campaigns may play in explaining differences in pandemic trajectories in temperate regions. Our model differentiates between the nature of vaccine- and infection-acquired immunity. In particular, we assume that immunity triggered by infection elicits heterologous cross-protection against viral shedding in addition to long-lasting neutralising antibody, whereas vaccination induces imperfect reduction in susceptibility. We employ an Approximate Bayesian Computation (ABC) framework to calibrate the model using data for pH1N12009 seroprevalence, relative subtype dominance, and annual IARs for Australia and the UK. Heterologous cross-protection substantially suppressed the pandemic IAR over the posterior, with the strength of protection against onward transmission inversely correlated with the initial reproduction number. We show that IAV pandemic timing relative to the usual seasonal influenza cycle influenced the size of the initial waves of pH1N12009 in temperate regions and the impact of vaccination campaigns.

An Observational Study on Cystic Alterations in Normal Dental Follicles Associated with Impacted Lower Third Molar for Early Intervention.

AIM: To evaluate the cystic changes in the radiographically normal dental follicle associated with impacted mandibular third molar. MATERIALS AND METHODS: This study was conducted on 80 patients. Samples were selected using a convenient sampling technique from the patients who had impacted mandibular third molars in Pell and Gregory's positions B and C, with follicular space less than 2.5 mm in diameter. After surgical removal of an impacted tooth, the dental follicle was sent for histopathologic evaluation. RESULTS: Pathologic alterations were found in 19% of cases out of 80 samples. Odontogenic keratocystic and dentigerous cystic changes were found in 7% of cases. A statistically significant cystic alteration was found in female patients and distoangular impacted teeth. CONCLUSION: This study shows a significant cystic alteration in the radiologically normal dental follicles. Clinical and radiographic features alone may not be a reliable indicator of the absence of pathology. Early intervention of impacted teeth will help to reduce morbidity due to the development of pathology. CLINICAL SIGNIFICANCE: This study will help educate patients on the risks of retaining impacted teeth, based on scientific facts, in order to minimize the risks and to assess the correlation of pathologic alterations with the depth of impaction and angular position of the impacted tooth.

Green-blue space exposure changes and impact on individual-level well-being and mental health: a population-wide dynamic longitudinal panel study with linked survey data.

Background: Cross-sectional evidence suggests that living near green and blue spaces benefits mental health; longitudinal evidence is limited. Objectives: To quantify the impact of changes in green and blue spaces on common mental health disorders, well-being and health service use. Design: A retrospective, dynamic longitudinal panel study. Setting: Wales, UK. Participants: An e-cohort comprising 99,682,902 observations of 2,801,483 adults (≥ 16 years) registered with a general practice in Wales (2008-2019). A 5312-strong 'National Survey for Wales (NSW) subgroup' was surveyed on well-being and visits to green and blue spaces. Main outcome measures: Common mental health disorders, general practice records; subjective well-being, Warwick-Edinburgh Mental Well-being Scale. Data sources: Common mental health disorder and use of general practice services were extracted quarterly from the Welsh Longitudinal General Practice Dataset. Annual ambient greenness exposure, enhanced vegetation index and access to green and blue spaces (2018) from planning and satellite data. Data were linked within the Secure Anonymised Information Linkage Databank. Methods: Multilevel regression models examined associations between exposure to green and blue spaces and common mental health disorders and use of general practice. For the National Survey for Wales subgroup, generalised linear models examined associations between exposure to green and blue spaces and subjective well-being and common mental health disorders. Results and conclusions: Our longitudinal analyses found no evidence that changes in green and blue spaces through time impacted on common mental health disorders. However, time-aggregated exposure to green and blue spaces contrasting differences between people were associated with subsequent common mental health disorders. Similarly, our cross-sectional findings add to growing evidence that residential green and blue spaces and visits are associated with well-being benefits: Greater ambient greenness (+ 1 enhanced vegetation index) was associated with lower likelihood of subsequently seeking care for a common mental health disorder [adjusted odds ratio (AOR) 0.80, 95% confidence interval, (CI) 0.80 to 0.81] and with well-being with a U-shaped relationship [Warwick-Edinburgh Mental Well-being Scale; enhanced vegetation index beta (adjusted) -10.15, 95% CI -17.13 to -3.17; EVI2 beta (quadratic term; adj.) 12.49, 95% CI 3.02 to 21.97]. Those who used green and blue spaces for leisure reported better well-being, with diminishing extra benefit with increasing time (Warwick-Edinburgh Mental Well-being Scale: time outdoors (hours) beta 0.88, 95% CI 0.53 to 1.24, time outdoors2 beta -0.06, 95% CI -0.11 to -0.01) and had 4% lower odds of seeking help for common mental health disorders (AOR 0.96, 95% CI 0.93 to 0.99). Those in urban areas benefited most from greater access to green and blue spaces (AOR 0.89, 95% CI 0.89 to 0.89). Those in material deprivation benefited most from leisure time outdoors (until approximately four hours per week; Warwick-Edinburgh Mental Well-being Scale: time outdoorsâ€…× in material deprivation: 1.41, 95% CI 0.39 to 2.43; time outdoors2 × in material deprivation -0.18, 95% CI -0.33 to -0.04) although well-being remained generally lower. Limitations: Longitudinal analyses were restricted by high baseline levels and limited temporal variation in ambient greenness in Wales. Changes in access to green and blue spaces could not be captured annually due to technical issues with national-level planning datasets. Future work: Further analyses could investigate mental health impacts in population subgroups potentially most sensitive to local changes in access to specific types of green and blue spaces. Deriving green and blue spaces changes from planning data is needed to overcome temporal uncertainties. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (Project number 16/07/07) and will be published in full in Public Health Research; Vol. 11, No. 10. Sarah Rodgers is part-funded by the NIHR Applied Research Collaboration North West Coast.

We investigated whether people who live near or visit green (parks, woodlands) and blue (riversides, beaches) spaces have fewer common mental health disorders (anxiety or depression), and better well-being. We considered whether changes in the amount of green and blue space around the home affected people's mental health. We assessed the availability of local green and blue spaces. Annual exposure and access to local green and blue spaces were extracted from planning and satellite data. We linked these data to anonymised health records of 2,801,483 adults registered with a general practice from 2008 to 2019, and to survey answers about leisure visits to natural environments and well-being. We found: people who lived in greener and bluer areas were less likely to seek help for a common mental health disorder than those in less green or blue areas, with those living in the most deprived areas benefiting the most people who used green and blue spaces for leisure, especially those with the greatest levels of deprivation, had better well-being and were less likely to seek help for common mental health disorders no evidence that changing amounts of green and blue space affected how likely people were to seek help for common mental health disorders; this may be because we found mostly small changes in green and blue space, and we may not have allowed enough time between moving home and recording mental health. We found evidence for relationships between green and blue space and mental health. However, some analyses were restricted due to lack of data on changes in green and blue spaces. An important finding was that people in deprived communities appear to benefit the most. Provision of green and blue spaces could be a strategy to improve the mental health of people living in disadvantaged areas.

Crystallographic fragment screening in academic cancer drug discovery.

Fragment-based drug discovery (FBDD) has brought several drugs to the clinic, notably to target proteins once considered to be challenging, or even undruggable. Screening in FBDD relies upon observing and/or measuring weak (millimolar-scale) binding events using biophysical techniques or crystallographic fragment screening. This latter structural approach provides no information about binding affinity but can reveal binding mode and atomic detail on protein-fragment interactions to accelerate hit-to-lead development. In recent years, high-throughput platforms have been developed at synchrotron facilities to screen thousands of fragment-soaked crystals. However, using accessible manual techniques it is possible to run informative, smaller-scale screens within an academic lab setting. This chapter describes general protocols for home laboratory-scale fragment screening, from fragment soaking through to structure solution and, where appropriate, signposts to background, protocols or alternatives elsewhere.

Nature-based biopsychosocial resilience: An integrative theoretical framework for research on nature and health.

Nature-based solutions including urban forests and wetlands can help communities cope better with climate change and other environmental stressors by enhancing social-ecological resilience. Natural ecosystems, settings, elements and affordances can also help individuals become more personally resilient to a variety of stressors, although the mechanisms underpinning individual-level nature-based resilience, and their relations to social-ecological resilience, are not well articulated. We propose 'nature-based biopsychosocial resilience theory' (NBRT) to address these gaps. Our framework begins by suggesting that individual-level resilience can refer to both: a) a person's set of adaptive resources; and b) the processes by which these resources are deployed. Drawing on existing nature-health perspectives, we argue that nature contact can support individuals build and maintain biological, psychological, and social (i.e. biopsychosocial) resilience-related resources. Together with nature-based social-ecological resilience, these biopsychosocial resilience resources can: i) reduce the risk of various stressors (preventive resilience); ii) enhance adaptive reactions to stressful circumstances (response resilience), and/or iii) facilitate more rapid and/or complete recovery from stress (recovery resilience). Reference to these three resilience processes supports integration across more familiar pathways involving harm reduction, capacity building, and restoration. Evidence in support of the theory, potential interventions to promote nature-based biopsychosocial resilience, and issues that require further consideration are discussed.

Ambient greenness, access to local green spaces, and subsequent mental health: a 10-year longitudinal dynamic panel study of 2·3 million adults in Wales.

BACKGROUND: Living in greener areas, or close to green and blue spaces (GBS; eg, parks, lakes, or beaches), is associated with better mental health, but longitudinal evidence when GBS exposures precede outcomes is less available. We aimed to analyse the effect of living in or moving to areas with more green space or better access to GBS on subsequent adult mental health over time, while explicitly considering health inequalities. METHODS: A cohort of the people in Wales, UK (≥16 years; n=2 341 591) was constructed from electronic health record data sources from Jan 1, 2008 to Oct 31, 2019, comprising 19 141 896 person-years of follow-up. Household ambient greenness (Enhanced Vegetation Index [EVI]), access to GBS (counts, distance to nearest), and common mental health disorders (CMD, based on a validated algorithm combining current diagnoses or symptoms of anxiety or depression [treated or untreated in the preceding 1-year period], or treatment of historical diagnoses from before the current cohort [up to 8 years previously, to 2000], where diagnosis preceded treatment) were record-linked. Cumulative exposure values were created for each adult, censoring for CMD, migration out of Wales, death, or end of cohort. Exposure and CMD associations were evaluated using multivariate logistic regression, stratified by area-level deprivation. FINDINGS: After adjustment, exposure to greater ambient greenness over time (+0·1 increased EVI on a 0-1 scale) was associated with lower odds of subsequent CMD (adjusted odds ratio 0·80, 95% CI 0·80-0·81), where CMD was based on a combination of current diagnoses or symptoms (treated or untreated in the preceding 1-year period), or treatments. Ten percentile points more access to GBS was associated with lower odds of a later CMD (0·93, 0·93-0·93). Every additional 360 m to the nearest GBS was associated with higher odds of CMD (1·05, 1·04-1·05). We found that positive effects of GBS on mental health appeared to be greater in more deprived quintiles. INTERPRETATION: Ambient exposure is associated with the greatest reduced risk of CMD, particularly for those who live in deprived communities. These findings support authorities responsible for GBS, who are attempting to engage planners and policy makers, to ensure GBS meets residents' needs. FUNDING: National Institute for Health and Care Research Public Health Research programme.

Targeting Cytotoxic Agents through EGFR-Mediated Covalent Binding and Release.

A major drawback of cytotoxic chemotherapy is the lack of selectivity toward noncancerous cells. The targeted delivery of cytotoxic drugs to tumor cells is a longstanding goal in cancer research. We proposed that covalent inhibitors could be adapted to deliver cytotoxic agents, conjugated to the ß-position of the Michael acceptor, via an addition-elimination mechanism promoted by covalent binding. Studies on model systems showed that conjugated 5-fluorouracil (5FU) could be released upon thiol addition in relevant time scales. A series of covalent epidermal growth factor receptor (EGFR) inhibitors were synthesized as their 5FU derivatives. Achieving the desired release of 5FU was demonstrated to depend on the electronics and geometry of the compounds. Mass spectrometry and NMR studies demonstrated an anilinoquinazoline acrylate ester conjugate bound to EGFR with the release of 5FU. This work establishes that acrylates can be used to release conjugated molecules upon covalent binding to proteins and could be used to develop targeted therapeutics.

Telehealth Interventions in Head and Neck Cancer Patients: A Systematic Review.

BACKGROUND: Head and neck cancer (HNC) and its treatments often result in adverse effects that impair a patient's quality of life. Although intensive rehabilitative strategies can be used, their applicability can be limited due to patient-specific and socioeconomic barriers. Telehealth interventions represent a possible novel approach to increase access to these services and improve posttreatment quality of life in the HNC population. OBJECTIVE: The objective of this systematic review was to identify studies investigating telemedicine-based interventions for HNC patients to determine whether there is a consensus concerning the cost-effectiveness, clinical utility, and accessibility of this model for rehabilitation. METHODS: PubMed, EMBASE, Web of Science, and CINAHL were used to identify literature without time limit for publication. A critical appraisal of individual sources was conducted by 2 reviewers. Sixteen studies met inclusion criteria. RESULTS: Studies related to telehealth interventions in the HNC population are limited. Salient themes included feasibility of telehealth as an intervention, effects on self-management and knowledge, impact on quality of life, physical and psychiatric symptoms, and cost. CONCLUSION: Although the current literature presents promising data, indicating that telehealth interventions may be both effective and cost-efficient in the management of HNC patients, more research is needed to definitively elucidate their role in management. IMPLICATIONS FOR PRACTICE: Telehealth interventions are valuable for clinicians as an alternative to expand access to care across the cancer continuum, to strengthen patients' knowledge and consequently their self-management, and to provide continuity of services as well as for remote monitoring of symptoms and response to treatment.