Contemporary Assessment of Energy Degeneracy in Orbital Mixing with Tetravalent f-Block Compounds.

The f block is a comparatively understudied group of elements that find applications in many areas. Continued development of technologies involving the lanthanides (Ln) and actinides (An) requires a better fundamental understanding of their chemistry. Specifically, characterizing the electronic structure of the f elements presents a significant challenge due to the spatially core-like but energetically valence-like nature of the f orbitals. This duality led f-block scientists to hypothesize for decades that f-block chemistry is dominated by ionic metal-ligand interactions with little covalency because canonical covalent interactions require both spatial orbital overlap and orbital energy degeneracy. Recent studies on An compounds have suggested that An ions can engage in appreciable orbital mixing between An 5f and ligand orbitals, which was attributed to "energy-degeneracy-driven covalency". This model of bonding has since been a topic of debate because different computational methods have yielded results that support and refute the energy-degeneracy-driven covalency model. In this Viewpoint, literatures concerning the metal- and ligand-edge X-ray absorption near-edge structure (XANES) of five tetravalent f-block systems─MO2 (M = Ln, An), LnF4, MCl62-, and [Ln(NP(pip)3)4]─are compiled and discussed to explore metal-ligand bonding in f-block compounds through experimental metrics. Based on spectral assignments from a variety of theoretical models, covalency is seen to decrease from CeO2 and PrO2 to TbO2 through weaker ligand-to-metal charge-transfer (LMCT) interactions, while these LMCT interactions are not observed in the trivalent Ln sesquixodes until Yb. In comparison, while XANES characterization of AnO2 compounds is scarce, computational modeling of available X-ray absorption spectra suggests that covalency among AnO2 reaches a maximum between Am and Cm. Moreover, a decrease in covalency is observed upon changing ligands while maintaining an isostructural coordination environment from CeO2 to CeF4. These results could allude to the importance of orbital energy degeneracy in f-block bonding, but there are a variety of data gaps and conflicting results from different modeling techniques that need to be addressed before broad conclusions can be drawn.

Evaluation of a Multisectoral Health Security Alliance Program Through Perceptions of Member States: African Partnership Outbreak Response Alliance (APORA).

INTRODUCTION: U.S. DoD global health engagements offer opportunities for strategic engagement and building capability in collaboration with foreign military and civilian counterparts. Global health engagement activities can take the form of health security alliances and allow the USA and its allies and partners to prepare for, mitigate, and respond to emerging biothreats and other harmful health events that may negatively impact national security. One such example is the African Partnership Outbreak Response Alliance (APORA), which was designed to expand African Partner Nation militaries' infectious disease outbreak response capabilities. This publication evaluates the development, implementation, and outcomes of APORA to better understand the program's effectiveness in developing Partner Nation medical capabilities and the efficacy of health security alliances more broadly. MATERIALS AND METHODS: Key informant interviews, focus groups, and questionnaires were used to collect responses from a sample of participants who attended an in-person APORA event in May 2022. The research team conducted thematic analysis of all responses to identify common themes and sub-themes in participants' perspectives and to elucidate findings and recommendations for future endeavors. RESULTS: The analysis determined that participants attended the APORA event primarily to disseminate and apply knowledge, skills, and abilities gained at the event to their own health system structures. Overall, participants indicated that APORA contributed to their countries' military medical and civilian cooperation, as well as their countries' military medical capabilities. Longer-term partners (i.e., 4+ years of APORA membership) agreed more strongly with these sentiments; newer partners (i.e., 1-3 years of APORA membership) were more likely to be neutral or agree to some extent. Participants also valued the opportunity to solidify global, regional, local, and peer partnerships and considered the ability to create partnerships of great importance to their countries' national health security. Language barriers were often listed as a hindrance to event participation and the overall integration of a regional health system response. Participants also cited resource scarcity, network erosion (particularly because of the coronavirus disease 2019 pandemic), and a lack of disseminating and communicating value-add in how APORA could/is providing to their member countries' health systems as key barriers. CONCLUSIONS: As a whole, these findings support APORA's objectives to develop and leverage partnerships to support medical capacity building, promote collaboration between military and civilian sectors, and increase access to opportunities and financial resources. Further evaluation is required to capture additional civilian perspectives while continuing to expand upon military perspectives in order to produce more generalizable findings. That said, this study enables key stakeholders to understand how to strengthen and expand future alliances to improve both health and security outcomes.

Vibrational anisotropy decay resolves rare earth binding induced conformational change in DTPA.

Elucidating the relationship between metal-ligand interactions and the associated conformational change of the ligand is critical for understanding the separation of lanthanides via ion binding. Here we examine DTPA, a multidentate ligand that binds lanthanides, in its free and metal bound conformations using ultrafast polarization dependent vibrational spectroscopy. The polarization dependent pump-probe spectra were analyzed to extract the isotropic and anisotropic response of DTPA's carbonyl groups in the 1550-1650 cm-1 spectral region. The isotropic response reports on the population relaxation of the carbonyl stretching modes. We find that the isotropic response is influenced by the identity of the metal ion. The anisotropy decay of the carbonyl stretching modes reveals a faster decay in the lanthanide-DTPA complexes than in the free DTPA ligand. We attribute the anisotropy decay to energy transfer among the different carbonyl sites - where the conformational change results in an increased coupling between the carbonyl sites of metal-bound DTPA complexes. DFT calculations and theoretical simulations of energy transfer suggest that the carbonyl sites are more strongly coupled in the metal-bound conformations compared to the free DTPA. The stronger coupling in the metal bound DTPA conformation leads to efficient energy transfer among the different carbonyl sites. Comparing the rate of anisotropy decay across the series of metal bound DTPA complexes we find that the anisotropy is sensitive to the charge density of the central metal ion, and thus can serve as a molecular scale reporter for lanthanide ion binding.

Identification and Characterization of CC-AMP1-like and CC-AMP2-like Peptides in Capsicum spp.

Antimicrobial peptides (AMPs) are compounds with a variety of bioactive properties. Especially promising are their antibacterial activities, often toward drug-resistant pathogens. Across different AMP sources, AMPs expressed within plants are relatively underexplored with a limited number of plant AMP families identified. Recently, we identified the novel AMPs CC-AMP1 and CC-AMP2 in ghost pepper plants (Capsicum chinense x frutescens), exerting promising antibacterial activity and not classifying into any known plant AMP family. Herein, AMPs related to CC-AMP1 and CC-AMP2 were identified within both Capsicum annuum and Capsicum baccatum. In silico predictions throughout plants were utilized to illustrate that CC-AMP1-like and CC-AMP2-like peptides belong to two broader AMP families, with three-dimensional structural predictions indicating that CC-AMP1-like peptides comprise a novel subfamily of α-hairpinins. The antibacterial activities of several closely related CC-AMP1-like peptides were compared with a truncated version of CC-AMP1 possessing significantly more activity than the full peptide. This truncated peptide was further characterized to possess broad-spectrum antibacterial activity against clinically relevant ESKAPE pathogens. These findings illustrate the value in continued study of plant AMPs toward characterization of novel AMP families, with CC-AMP1-like peptides possessing promising bioactivity.

Steroid Drugs Inhibit Bacterial Respiratory Oxidases and Are Lethal Toward Methicillin-Resistant Staphylococcus aureus.

BACKGROUND: Cytochrome bd complexes are respiratory oxidases found exclusively in prokaryotes that are important during infection for numerous bacterial pathogens. METHODS: In silico docking was employed to screen approved drugs for their ability to bind to the quinol site of Escherichia coli cytochrome bd-I. Respiratory inhibition was assessed with oxygen electrodes using membranes isolated from E. coli and methicillin-resistant Staphylococcus aureus strains expressing single respiratory oxidases (ie, cytochromes bd, bo', or aa3). Growth/viability assays were used to measure bacteriostatic and bactericidal effects. RESULTS: The steroid drugs ethinylestradiol and quinestrol inhibited E. coli bd-I activity with median inhibitory concentration (IC50) values of 47 ± 28.9 µg/mL (158 ± 97.2 µM) and 0.2 ± 0.04 µg/mL (0.5 ± 0.1 µM), respectively. Quinestrol inhibited growth of an E. coli "bd-I only" strain with an IC50 of 0.06 ± 0.02 µg/mL (0.2 ± 0.07 µM). Growth of an S. aureus "bd only" strain was inhibited by quinestrol with an IC50 of 2.2 ± 0.43 µg/mL (6.0 ± 1.2 µM). Quinestrol exhibited potent bactericidal effects against S. aureus but not E. coli. CONCLUSIONS: Quinestrol inhibits cytochrome bd in E. coli and S. aureus membranes and inhibits the growth of both species, yet is only bactericidal toward S. aureus.

Draft genome sequence of a highly proteolytic Staphylococcus aureus USA300 isolate from human urine.

The secreted proteases of Staphylococcus aureus have been shown to be critical during infection. Here, we present the draft genome sequence of S. aureus TGH337, a hyper-proteolytic USA300 strain isolated from human urine.

Positive Mental Health of Migrants in the UK during COVID-19: A Review.

COVID-19 impacted the mental health of many people in the UK. The negative impact was especially substantial among vulnerable population groups, including migrants. While research has focused on the negative aspects of mental health during the pandemic, the positive mental health of migrants in the UK during COVID-19 remained to be evaluated. This review aimed to identify literature that focused on positive mental health, and thematically synthesise the findings to understand what positive mental health approaches were employed to support specific outcomes during the pandemic for them to survive in this difficult time. Medline, Embase, and PsycINFO were searched using terms including "mental health", "migrants", and "COVID-19". The Critical Appraisal Skills Programme checklist was used to assess the quality of the included studies. There were only two studies examining the positive mental health of UK migrants during this period. They describe approaches such as religious beliefs, passion for and acknowledgement of their job, learning new things, being physically active, social media, and social activities, producing outcomes such as inner peace, confidence, well-being, and a sense of belonging. The quality of the included studies was high. More research about positive mental health in migrants in the UK during the pandemic is needed.

Comprehensive geriatric assessment delivered by advanced nursing practitioners within primary care setting: a mixed-methods pilot feasibility randomised controlled trial.

BACKGROUND: Comprehensive Geriatric Assessment (CGA)is a widely accepted intervention for frailty and can be cost-effective within a primary care setting. OBJECTIVE: To explore the feasibility of identifying older adults with frailty and assess the subsequent implementation of a tailored CGA with care and support plan by Advanced Nursing Practitioners (ANPs). METHODS: A mixed-method parallel randomised controlled trial was conducted. Participants were recruited from two General Practice (GP) centres between January and June 2019. Older adults with confirmed frailty, as assessed by practice nurses, were randomised, using a web service, to the intervention or treatment-as-usual (TAU) groups for six months with an interim and a final review. Data were collected on feasibility, health service usage, function, quality of life, loneliness, and participants' experience and perception of the intervention. Non-parametric tests were used to analyse within and between-group differences. P-values were adjusted to account for type I error. Thematic analysis of qualitative data was conducted. RESULTS: One hundred sixty four older adults were invited to participate, of which 44.5% (n = 72) were randomised to either the TAU (n = 37) or intervention (n = 35) groups. All participants in the intervention group were given the baseline, interim and final reviews. Eight participants in each group were lost to post-intervention outcome assessment. The health service use (i.e. hospital admissions, GP/emergency calls and GP/Accident Emergency attendance) was slightly higher in the TAU group; however, none of the outcome data showed statistical significance between-group differences. The TAU group showed a deterioration in the total functional independence and its motor and cognition components post-intervention (p < .05), though the role limitation due to physical function and pain outcomes improved (p < .05). The qualitative findings indicate that participants appreciated the consistency of care provided by ANPs, experienced positive therapeutic relationship and were connected to wider services. DISCUSSION: Frailty identification and intervention delivery in the community by ANPs were feasible. The study shows that older adults with frailty living in the community might benefit from intervention delivered by ANPs. It is suggested to examine the cost-effectiveness of the intervention in sufficiently powered future research. TRIAL REGISTRATIONS: The protocol is available at clinicaltirals.gov, ID: NCT03394534; 09/01/2018.

The identification of two M20B family peptidases required for full virulence in Staphylococcus aureus.

We have previously demonstrated that deletion of an intracellular leucine aminopeptidase results in attenuated virulence of S. aureus. Herein we explore the role of 10 other aminopeptidases in S. aureus pathogenesis. Using a human blood survival assay we identified mutations in two enzymes from the M20B family (PepT1 and PepT2) as having markedly decreased survival compared to the parent. We further reveal that pepT1, pepT2 and pepT1/2 mutant strains are impaired in their ability to resist phagocytosis by, and engender survival within, human macrophages. Using a co-infection model of murine sepsis, we demonstrate impairment of dissemination and survival for both single mutants that is even more pronounced in the double mutant. We show that these enzymes are localized to the cytosol and membrane but are not necessary for peptide-based nutrition, a hallmark of cell-associated aminopeptidases. Furthermore, none of the survival defects appear to be the result of altered virulence factor production. An exploration of their regulation reveals that both are controlled by known regulators of the S. aureus virulence process, including Agr, Rot and/or SarA, and that this cascade may be mediated by FarR. Structural modeling of PepT1 reveals it bears all the hallmarks of a tripeptidase, whilst PepT2 differs significantly in its catalytic pocket, suggesting a broader substrate preference. In sum, we have identified two M20B aminopeptidases that are integral to S. aureus pathogenesis. The future identification of protein and/or peptide targets for these proteases will be critical to understanding their important virulence impacting functions.

ATR protects ongoing and newly assembled DNA replication forks through distinct mechanisms.

The ATR kinase safeguards genomic integrity during S phase, but how ATR protects DNA replication forks remains incompletely understood. Here, we combine four distinct assays to analyze ATR functions at ongoing and newly assembled replication forks upon replication inhibition by hydroxyurea. At ongoing forks, ATR inhibitor (ATRi) increases MRE11- and EXO1-mediated nascent DNA degradation from PrimPol-generated, single-stranded DNA (ssDNA) gaps. ATRi also exposes template ssDNA through fork uncoupling and nascent DNA degradation. Electron microscopy reveals that ATRi reduces reversed forks by increasing gap-dependent nascent DNA degradation. At new forks, ATRi triggers MRE11- and CtIP-initiated template DNA degradation by EXO1, exposing nascent ssDNA. Upon PARP inhibition, ATRi preferentially exacerbates gap-dependent nascent DNA degradation at ongoing forks in BRCA1/2-deficient cells and disrupts the restored gap protection in BRCA1-deficient, PARP-inhibitor-resistant cells. Thus, ATR protects ongoing and new forks through distinct mechanisms, providing an extended view of ATR's functions in stabilizing replication forks.

Staphylococcus aureus SigS Induces Expression of a Regulatory Protein Pair That Modulates Its mRNA Stability.

SigS is the sole extracytoplasmic function sigma factor in Staphylococcus aureus and is necessary for virulence, immune evasion, and adaptation to toxic chemicals and environmental stressors. Despite the contribution of SigS to a myriad of critical phenotypes, the downstream effectors of SigS-dependent pathogenesis, immune evasion, and stress adaptation remain elusive. To address this knowledge gap, we analyzed the S. aureus transcriptome following transient overexpression of SigS. We identified a bicistronic transcript, upregulated 1,000-fold, containing two midsized genes, each containing single domains of unknown function (DUFs). We renamed these genes SigS-regulated orfA (sroA) and SigS-regulated orfB (sroB). We demonstrated that SigS regulation of the sroAB operon is direct by using in vitro transcription analysis. Using Northern blot analysis, we also demonstrated that SroA and SroB have opposing autoregulatory functions on the transcriptional architecture of the sigS locus, with SroA stimulating SigS mRNA levels and SroB stimulating s750 (SigS antisense) levels. We hypothesized that these opposing regulatory effects were due to a direct interaction. We subsequently demonstrated a direct interaction between SroA and SroB using an in vivo surrogate genetics approach via bacterial adenylate cyclase-based two-hybrid (BACTH) analysis. We demonstrated that the SroA effect on SigS is at the posttranscriptional level of mRNA stability, highlighting a mechanism likely used by S. aureus to tightly control SigS levels. Finally, we demonstrate that the sroAB locus promotes virulence in a murine pneumonia model of infection. IMPORTANCE SigS is necessary for S. aureus virulence, immune evasion, and adaptation to chemical and environmental stressors. These processes are critically important for the ability of S. aureus to cause disease. However, the SigS-dependent transcriptome has not been identified, hindering our ability to identify downstream effectors of SigS that contribute to these pathogenic and adaptive phenotypes. Here, we identify a regulatory protein pair that is a major direct target of SigS, known as SroA and SroB. SroA also acts to stimulate SigS expression at the posttranscriptional level of RNA turnover, providing insight into intrinsically low levels of SigS. The discovery of SroA and SroB increases our understanding of SigS and the S. aureus pathogenesis process.

A double-blind, sham-controlled, trial of home-administered rhythmic 10-Hz median nerve stimulation for the reduction of tics, and suppression of the urge-to-tic, in individuals with Tourette syndrome and chronic tic disorder.

Tourette syndrome (TS) and chronic tic disorder (CTD) are neurological disorders of childhood onset characterized by the occurrence of tics; repetitive, purposeless, movements or vocalizations of short duration which can occur many times throughout a day. Currently, effective treatment for tic disorders is an area of considerable unmet clinical need. We aimed to evaluate the efficacy of a home-administered neuromodulation treatment for tics involving the delivery of rhythmic pulse trains of median nerve stimulation (MNS) delivered via a wearable 'watch-like' device worn at the wrist. We conducted a UK-wide parallel double-blind sham-controlled trial for the reduction of tics in individuals with tic disorder. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve for a pre-determined duration each day, and was intended to be used by each participant in their home once each day, 5 days each week, for a period of 4 weeks. Between 18th March 2022 and 26th September 2022, 135 participants (45 per group) were initially allocated, using stratified randomization, to one of the following groups; active stimulation; sham stimulation or to a waitlist (i.e. treatment as usual) control group. Recruited participants were individuals with confirmed or suspected TS/CTD aged 12 years of age or upward with moderate to severe tics. Researchers involved in the collection or processing of measurement outcomes and assessing the outcomes, as well as participants in the active and sham groups and their legal guardians were all blind to the group allocation. The primary outcome measure used to assess the 'offline' or treatment effect of stimulation was the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS) assessed at the conclusion of 4 weeks of stimulation. The primary outcome measure used to assess the 'online' effects of stimulation was tic frequency, measured as the number of tics per minute (TPM) observed, based upon blind analysis of daily video recordings obtained while stimulation was delivered. The results demonstrated that after 4-week stimulation, tic severity (YGTSS-TTSS) had reduced by 7.1 points (35 percentile reduction) for the active stimulation group compared to 2.13/2.11 points for the sham stimulation and waitlist control groups. The reduction in YGTSS-TTSS for the active stimulation group was substantially larger, clinically meaningful (effect size = .5) and statistically significant (p = .02) compared to both the sham stimulation and waitlist control groups, which did not differ from one another (effect size = -.03). Furthermore, blind analyses of video recordings demonstrated that tic frequency (tics per minute) reduced substantially (-15.6 TPM) during active stimulation compared to sham stimulation (-7.7 TPM). This difference represents a statistically significant (p < .03) and clinically meaningful reduction in tic frequency (>25 percentile reduction: effect size = .3). These findings indicate that home-administered rhythmic MNS delivered through a wearable wrist-worn device has the potential to be an effective community-based treatment for tic disorders.

RAD51 bypasses the CMG helicase to promote replication fork reversal.

Replication fork reversal safeguards genome integrity as a replication stress response. DNA translocases and the RAD51 recombinase catalyze reversal. However, it remains unknown why RAD51 is required and what happens to the replication machinery during reversal. We find that RAD51 uses its strand exchange activity to circumvent the replicative helicase, which remains bound to the stalled fork. RAD51 is not required for fork reversal if the helicase is unloaded. Thus, we propose that RAD51 creates a parental DNA duplex behind the helicase that is used as a substrate by the DNA translocases for branch migration to create a reversed fork structure. Our data explain how fork reversal happens while maintaining the helicase in a position poised to restart DNA synthesis and complete genome duplication.

Probing Unexpected Reactivity in Radiometal Chemistry: Indium-111-Mediated Hydrolysis of Hybrid Cyclen-Hydroxypyridinone Ligands.

Chelators based on hydroxypyridinones have utility in incorporating radioactive metal ions into diagnostic and therapeutic agents used in nuclear medicine. Over the course of our hydroxypyridinone studies, we have prepared two novel chelators, consisting of a cyclen (1,4,7,10-tetraazacyclododecane) ring bearing two pendant hydroxypyridinone groups, appended via methylene acetamide motifs at either the 1,4-positions (L1) or 1,7-positions (L2) of the cyclen ring. In radiolabeling reactions of L1 or L2 with the γ-emitting radioisotope, [111In]In3+, we have observed radiometal-mediated hydrolysis of a single amide group of either L1 or L2. The reaction of either [111In]In3+ or [natIn]In3+ with either L1 or L2, in aqueous alkaline solutions at 80 °C, initially results in formation of [In(L1)]+ or [In(L2)]+, respectively. Over time, each of these species undergoes In3+-mediated hydrolysis of a single amide group to yield species in which In3+ remains coordinated to the resultant chelator, which consists of a cyclen ring bearing a single hydroxypyridinone group and a single carboxylate group. The reactivity toward hydrolysis is higher for the L1 complex compared to that for the L2 complex. Density functional theory calculations corroborate these experimental findings and importantly indicate that the activation energy required for the hydrolysis of L1 is significantly lower than that required for L2. This is the first reported example of a chelator undergoing radiometal-mediated hydrolysis to form a radiometalated complex. It is possible that metal-mediated amide bond cleavage is a source of instability in other radiotracers, particularly those in which radiometal complexation occurs in aqueous, basic solutions at high temperatures. This study highlights the importance of appropriate characterization of radiolabeled products.

Ethnic Minorities' Experiences of Cardiac Rehabilitation: A Scoping Review.

Cardiac rehabilitation (CR) can improve cardiovascular risk factors, decrease cardiac mortality, and promote healthy lifestyle behaviours. However, services remain underutilized by groups of ethnic minorities. The purpose of the study was to identify patients' personal CR experiences to identify the differences CR makes towards minorities' lifestyle. An initial electronic search was performed in 2021 for papers ranging from 2008-2020 across specific databases, including PubMed, EMBASE, APA PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Medline. Google Scholar was also used to supplement the search process and to identify studies performed within grey literature. A total of 1230 records were screened, of which 40 were assessed for eligibility. The final sample consisted of seven qualitative design studies that were identified for inclusion in this review. Based on patient personal experiences, this review identified that ethnic minorities continue to remain disadvantaged when accessing healthcare interventions, primarily as a result of cultural behaviours, linguistic barriers, socioeconomic status, religious and fatalistic beliefs, and low physician referral rates. More research is needed to elucidate this phenomenon and address these factors faced by ethnic minorities.

Comparing the Mental Health of Healthcare Students: Mental Health Shame and Self-compassion in Counselling, Occupational Therapy, Nursing and Social Work Students.

Poor mental health of healthcare students is a cause for concern in many universities. Though previous research has identified mental health shame and self-compassion as critical in this student group, how these variables differ across different healthcare disciplines remains to be evaluated. Healthcare students (n = 344; counselling, occupational therapy, social work and nursing) completed measures regarding these variables. MANOVA and regression analyses were performed. (1) Counselling and nursing students were more depressed than occupational therapy students; (2) nursing students were more anxious than occupational therapy and social work students; (3) occupational therapy students had more positive attitudes towards mental health than the others; and (4) nursing students worried about their own reputation associated with their family more than counselling students. Self-compassion was the strongest predictor of mental health in all groups; however, the effect sizes varied: largest in nursing and smallest in social work students. Findings will help inform effective interventions for students in each healthcare discipline.

NEDDylated Cullin 3 mediates the adaptive response to topoisomerase 1 inhibitors.

DNA topoisomerase 1 (TOP11) inhibitors are mainstays of anticancer therapy. These drugs trap TOP1 on DNA, stabilizing the TOP1-cleavage complex (TOP1-cc). The accumulation of TOP1-ccs perturbs DNA replication fork progression, leading to DNA breaks and cell death. By analyzing the genomic occupancy and activity of TOP1, we show that cells adapt to treatment with multiple doses of TOP1 inhibitor by promoting the degradation of TOP1-ccs, allowing cells to better tolerate subsequent doses of TOP1 inhibitor. The E3-RING Cullin 3 ligase in complex with the BTBD1 and BTBD2 adaptor proteins promotes TOP1-cc ubiquitination and subsequent proteasomal degradation. NEDDylation of Cullin 3 activates this pathway, and inhibition of protein NEDDylation or depletion of Cullin 3 sensitizes cancer cells to TOP1 inhibitors. Collectively, our data uncover a previously unidentified NEDD8-Cullin 3 pathway involved in the adaptive response to TOP1 inhibitors, which can be targeted to improve the efficacy of TOP1 drugs in cancer therapy.

'This Is What the Colour Green Smells Like!': Urban Forest Bathing Improved Adolescent Nature Connection and Wellbeing.

BACKGROUND: Research suggests that an early connection with nature can benefit wellbeing into adulthood. However, there is less research assessing whether adolescents benefit from formal nature connection interventions such as forest bathing (slow mindful nature walks). This research aimed to assess whether an urban nature connection intervention (called ParkBathe) could improve adolescents' nature connection and wellbeing. METHOD: In an experimental repeated measures design, 44 adolescents sampled opportunistically from Scouts groups, completed surveys and interviews before and after experiencing an urban nature connection intervention. RESULTS: Paired-samples t-tests between baseline and post-intervention survey scores revealed statistically significant improvements in anxiety (13% reduction); rumination (44% reduction); scepticism (17% reduction); nature connection (25% increase); and social connection (12% increase). The largest effect size was found for nature connection. Interviews revealed that before the session, participants had a mixed understanding and expectations of the intervention. CONCLUSIONS: After the session, the participants expressed enjoying the social aspects of being part of a group and being present in the moment by noticing nature. They expressed the effects of this as immediately calming and relaxing. Urban forest bathing improved nature connection and wellbeing in adolescents and could be implemented and/or signposted by schools and youth charities.

The Feasibility and Impact of Practising Online Forest Bathing to Improve Anxiety, Rumination, Social Connection and Long-COVID Symptoms: A Pilot Study.

BACKGROUND: Long-COVID affects over 144 million people globally. In the absence of treatments, there is a need to establish the efficacy of therapies that improve patient outcomes. Forest bathing has been demonstrated to improve physical and mental outcomes but there is no evidence in Long-COVID patients. Accordingly, this pilot study sought to determine the feasibility and effectiveness of online forest bathing in adults with Long-COVID. METHODS: Feasibility was assessed by monitoring retention rates and participant feedback. In a waitlist controlled, repeated measures design, 22 Long-COVID patients completed weekly online surveys during a four-week waitlist control period, before engaging in four weekly online forest bathing sessions, completing post-intervention surveys following each session. RESULTS: In terms of retention, 27% did not provide post-intervention data, reasons for non-adherence were: feeling too ill, having medical appointments, or having career responsibilities. Compared with the waitlist control period, there were statistically significant improvements in Anxiety (49% decrease), Rumination (48% decrease), Social Connection (78% increase), and Long-COVID symptoms (22% decrease). Written qualitative comments indicated that participants experienced feelings of calm and joy, felt more connected socially and with nature, and experienced a break from the pain and rumination surrounding their illness. CONCLUSIONS: Online Forest bathing resulted in significant improvements in well-being and symptom severity and could be considered an accessible and inexpensive adjunct therapy for Long-COVID patients. Where people have limited access to in-person nature, virtual nature may offer an alternative to improve health and well-being outcomes.