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A key challenge in the development of precision medicine is defining the phenotypic consequences of pharmacological modulation of specific target macromolecules. To address this issue, a variety of genetic, molecular and chemical tools can be used. All of these approaches can produce misleading results if the specificity of the tools is not well understood and the proper controls are not performed. In this paper we illustrate these general themes by providing detailed studies of small molecule inhibitors of the enzymatic activity of two members of the SMYD branch of the protein lysine methyltransferases, SMYD2 and SMYD3. We show that tool compounds as well as CRISPR/Cas9 fail to reproduce many of the cell proliferation findings associated with SMYD2 and SMYD3 inhibition previously obtained with RNAi based approaches and with early stage chemical probes.

WHSC1 is a histone methyltransferase that is responsible for mono- and dimethylation of lysine 36 on histone H3 and has been implicated as a driver in a variety of hematological and solid tumors. Currently, there is a complete lack of validated chemical matter for this important drug discovery target. Herein we report on the first fully validated WHSC1 inhibitor, PTD2, a norleucine-containing peptide derived from the histone H4 sequence. This peptide exhibits micromolar affinity towards WHSC1 in biochemical and biophysical assays. Furthermore, a crystal structure was solved with the peptide in complex with SAM and the SET domain of WHSC1L1. This inhibitor is an important first step in creating potent, selective WHSC1 tool compounds for the purposes of understanding the complex biology in relation to human disease.

[This corrects the article DOI: 10.1371/journal.pone.0158888.].

Abstract Cancer is highlighted as a major global health challenge in the XXI century. The cyclooxygenase-2 (COX-2) enzyme rises as a widespread tumor progression marker. Celecoxib (CXB) is a selective COX-2 inhibitor used in adjuvant cancer therapy, but high concentrations are required in humans. In this sense, the development of nanocarriers has been proposed once they can improve the biopharmaceutical, pharmacokinetic and pharmacological properties of drugs. In this context, this article reviews the progress in the development of CXB-loaded nanocarriers over the past decade and their prospects. Recent advances in the field of CXB-loaded nanocarriers demonstrate the use of complex formulations and the increasing importance of in vivo studies. The types of CXB-loaded nanocarriers that have been developed are heterogeneous and based on polymers and lipids together or separately. It was found that the work on CXB-loaded nanocarriers is carried out using established techniques and raw materials, such as poly (lactic-co-glicolic acid), cholesterol, phospholipids and poly(ethyleneglycol). The main improvements that have been achieved are the use of cell surface ligands, the simultaneous delivery of different synergistic agents, and the presence of materials that can provide imaging properties and other advanced features. The combination of CXB with other anti-inflammatory drugs and/or apoptosis inducers appears to hold effective pharmacological promise. The greatest advance to date from a clinical perspective is the ability of CXB to enhance the cytotoxic effects of established chemotherapeutic agents. Graphical abstract

ABSTRACT Primary Aim To describe the features of implementation in the setting of primary care (PC) for physical activity (PA) interventions that improved total and moderate to vigorous PA (MVPA). Secondary Aim To assess the scalability potential of effective PC PA interventions. Method A comprehensive search was conducted across multiple electronic databases to identify relevant studies published between 2012 and 2023. Implementation‐related features were extracted, and the scalability potential of effective PC PA interventions was assessed using the Intervention Scalability Tool (ISAT) as a framework. Results Twenty‐six studies met the inclusion criteria after screening. Analysis of the implementation‐related features revealed that effective PC PA interventions showed promising reach with a mean participation rate of 43%. Effective PC PA interventions that increased PA were mostly delivered by nurses and were underpinned by the behavioural change techniques (BCTs) of goal setting, feedback and self‐monitoring. The scalability assessment revealed that remote‐based interventions and those delivered by nurses had moderate to high scores in the scalability domains of fidelity, reach and acceptability, delivery setting and workforce, implementation infrastructure and sustainability. Conclusion PC PA interventions, whether delivered remotely or face‐to‐face, show promise for increasing PA, especially when incorporating BCTs like goal setting and feedback. Using the ISAT, most interventions displayed promise for implementation at scale, but further examination is needed concerning the delivery setting, implementation infrastructure and sustainability of these interventions. Remote‐based (automated PA advice and mailed instructions) PA interventions and those delivered in contact with a nurse showed high scalability potential. Further work that examines the acceptability and effectiveness of other healthcare professionals in intervention delivery would be worthwhile, and more work is needed to assess the utility and effectiveness of remote‐based PA interventions in PC.

ObjectiveEstrogen-related receptor γ (ERRγ) is a metabolic regulator with no identified physiological ligands. This study investigates whether calcium is an ERRγ ligand that mediates the effects of glucagon and whether cadmium, which mimics the effects of calcium, disrupts metabolism through ERRγ.MethodHepG2, MCF-7, and HEK293T transfected with ERRγ were treated with glucagon, calcium, cadmium, ERRγ agonist, or ERRγ inhibitor. Cells were then collected for in vitro assays including real-time qPCR, Western blot, ChIP, immunofluorescence, mutational analysis, or gene set enrichment analysis. Molecular dynamics simulations were performed to study mutation sites.ResultsIn HepG2 cells, treatment with glucagon, calcium, or cadmium re-localized ERRγ to the cell nucleus, recruited ERRγ to estrogen-related response elements, induced the expression of ERRγ-regulated genes, and increased extracellular glucose that was blocked by an ERRγ antagonist. In MCF-7 cells and HEK293T cells transfected with ERRγ, similar treatments induced the expression of metabolic genes. Mutational analysis identified S303, T429, and E452 in the ligand-binding domain as potential interaction sites. Molecular dynamics simulations showed that calcium induced changes in ERRγ similar to ERRγ agonist.ConclusionThe results suggest that calcium is a potential ligand of ERRγ that mediates the effects of glucagon and cadmium disrupts metabolism through ERRγ.

The catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output. The enzymes that catalyze these activities are often contained within multiprotein complexes in nature. Two such multiprotein complexes, the polycomb repressive complex 2 (PRC2) methyltransferase and the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeler have been reported to act in opposition to each other during development and homeostasis. An imbalance in their activities induced by mutations/deletions in complex members (e.g. SMARCB1) has been suggested to be a pathogenic mechanism in certain human cancers. Here we show that preclinical models of synovial sarcoma-a cancer characterized by functional SMARCB1 loss via its displacement from the SWI/SNF complex through the pathognomonic SS18-SSX fusion protein-display sensitivity to pharmacologic inhibition of EZH2, the catalytic subunit of PRC2. Treatment with tazemetostat, a clinical-stage, selective and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity reverses a subset of synovial sarcoma gene expression and results in concentration-dependent cell growth inhibition and cell death specifically in SS18-SSX fusion-positive cells in vitro. Treatment of mice bearing either a cell line or two patient-derived xenograft models of synovial sarcoma leads to dose-dependent tumor growth inhibition with correlative inhibition of trimethylation levels of the EZH2-specific substrate, lysine 27 on histone H3. These data demonstrate a dependency of SS18-SSX-positive, SMARCB1-deficient synovial sarcomas on EZH2 enzymatic activity and suggests the potential utility of EZH2-targeted drugs in these genetically defined cancers.

Patients with non-Hodgkin lymphoma (NHL) are treated today with a cocktail of drugs referred to as CHOP (Cyclophosphamide, Hydroxyldaunorubicin, Oncovin, and Prednisone). Subsets of patients with NHL of germinal center origin bear oncogenic mutations in the EZH2 histone methyltransferase. Clinical testing of the EZH2 inhibitor EPZ-6438 has recently begun in patients. We report here that combining EPZ-6438 with CHOP in preclinical cell culture and mouse models results in dramatic synergy for cell killing in EZH2 mutant germinal center NHL cells. Surprisingly, we observe that much of this synergy is due to Prednisolone - a glucocorticoid receptor agonist (GRag) component of CHOP. Dramatic synergy was observed when EPZ-6438 is combined with Prednisolone alone, and a similar effect was observed with Dexamethasone, another GRag. Remarkably, the anti-proliferative effect of the EPZ-6438+GRag combination extends beyond EZH2 mutant-bearing cells to more generally impact germinal center NHL. These preclinical data reveal an unanticipated biological intersection between GR-mediated gene regulation and EZH2-mediated chromatin remodeling. The data also suggest the possibility of a significant and practical benefit of combining EZH2 inhibitors and GRag that warrants further investigation in a clinical setting.

Abstract Background Severe mental ill health (SMI) includes schizophrenia, bipolar disorder and schizoaffective disorder and is associated with premature deaths when compared to people without SMI. Over 70% of those deaths are attributed to preventable health conditions, which have the potential to be positively affected by the adoption of healthy behaviours, such as physical activity. People with SMI are generally less active than those without and face unique barriers to being physically active. Physical activity interventions for those with SMI demonstrate promise, however, there are important questions remaining about the potential feasibility and acceptability of a physical activity intervention embedded within existing NHS pathways. Method This is a two-arm multi-site randomised controlled feasibility trial, assessing the feasibility and acceptability of a co-produced physical activity intervention for a full-scale trial across geographically dispersed NHS mental health trusts in England. Participants will be randomly allocated via block, 1:1 randomisation, into either the intervention arm or the usual care arm. The usual care arm will continue to receive usual care throughout the trial, whilst the intervention arm will receive usual care plus the offer of a weekly, 18-week, physical activity intervention comprising walking and indoor activity sessions and community taster sessions. Another main component of the intervention includes one-to-one support. The primary outcome is to investigate the feasibility and acceptability of the intervention and to scale it up to a full-scale trial, using a short proforma provided to all intervention participants at follow-up, qualitative interviews with approximately 15 intervention participants and 5 interventions delivery staff, and data on intervention uptake, attendance, and attrition. Usual care data will also include recruitment and follow-up retention. Secondary outcome measures include physical activity and sedentary behaviours, body mass index, depression, anxiety, health-related quality of life, healthcare resource use, and adverse events. Outcome measures will be taken at baseline, three, and six-months post randomisation. Discussion This study will determine if the physical activity intervention is feasible and acceptable to both participants receiving the intervention and NHS staff who deliver it. Results will inform the design of a larger randomised controlled trial assessing the clinical and cost effectiveness of the intervention. Trial registration ISRCTN: ISRCTN83877229. Registered on 09.09.2022.

Before the invasion of the fall armyworm (FAW) Spodoptera frugiperda into Africa, smallholder farmers had been using indigenous practices such as applying fish soup to plants to manage stemborer pests. Although farmers have since begun adapting this practice against FAW, no attempt has been made to scientifically evaluate this practice. Therefore, we assessed the efficacy of applying fish soup to maize plants that were artificially infested with FAW under semi-field conditions. Our results showed that foliar damage is inversely correlated with the concentration of a fish soup and sugar solution, with the highest (100%) concentration resulting in the lowest foliar damage and the highest plant recovery. The FAW foliar damage results for maize plants treated with 100%, 50%, 10% fish soup and sugar, and distilled water were 46.3 ± 5.6, 51.1 ± 5.0, 71.6 ± 5.2, and 99.4 ± 0.4%, respectively, whereas plant recovery results from the same treatments were 35.2 ± 3.7, 31.1 ± 5.4, 20.0 ± 4.6, and 0.0 ± 0.0%, respectively. A concentration of fish soup and sugar solution of at least 25.9% was required to achieve the lowest foliar damage of 17.8% and peak plant recovery of 73.6%. Fish soup and sugar solutions attracted a wide range of insects, including potential natural enemies (predators and parasitoids) of FAW, in a dose-dependent manner. Maize plants treated with fish soup and sugar showed higher chlorophyll content and better growth than the control did. Proximate and chemical analysis showed that fish soup contains essential plant growth nutrients (e.g., nitrogen, phosphorus, and calcium). Through GC-MS analyses, we identified 76 volatile organic compounds in fish soup, of which 16 have been reported as insect attractants, highlighting their potential ecological significance. Therefore, the indigenous pest management practices for FAW, such as the use of fish soup, deserve particular attention. These practices could contribute to food security and improve the livelihoods of vulnerable communities. Further field validation studies, economic analyses, product development, and optimisation are therefore required to optimise the use of fish soup based on fish waste.

The endemic Afrotropical genus Dinapsis is revised, and seven new species are described and illustrated: D. bicolor van Noort & Shaw, sp. nov., D. gamka van Noort & Shaw, sp. nov., D. igneus van Noort & Shaw, sp. nov., D. spinitibia van Noort & Shaw, sp. nov., D. taita van Noort & Shaw, sp. nov., D. tricolor Shaw & van Noort, sp. nov., D. zulu Shaw & van Noort, sp. nov. The distribution of the Central African Republican species D. centralis Shaw & van Noort, 2009 is extended to include Cameroon, Kenya and Uganda. Dinapsis turneri Waterston, 1922, previously only known from the poorly preserved holotype female, is redescribed based on newly collected specimens. The distribution of this Western Cape species is extended to include the Eastern and Northern Cape provinces of South Africa. Four distinct species groups within the genus are proposed and diagnosed. An illustrated identification key to all described species of Dinapsis is provided. Online interactive Lucid keys to Afrotropical megalyrid genera and Dinapsis species are available at http://www.waspweb.org.

Summary: Background: Low levels of physical activity (PA) are associated with poorer health outcomes. The perioperative encounter (extending from initial contact in primary care to beyond discharge from hospital) is potentially a good time to intervene, but data regarding the effectiveness of interventions are scarce. To address this, we systematically reviewed existing literature to evaluate the effectiveness of interventions applied perioperatively to facilitate PA in the medium to long-term (at least six months after the intervention). Methods: In this systematic review and meta-analysis, we searched Central Register of Controlled Trials (CENTRAL, Cochrane Library), MEDLINE, CINAHL, Embase, PsycInfo, and SPORTDiscus from database inception to October 22nd 2020, with an updated search done on August 4th 2022. We searched clinical trials registers, and conducted forward- and backward-citation searches. We included randomised controlled trials and quasi-randomised trials comparing PA interventions with usual care, or another PA intervention, in adults who were scheduled for, or had recently undergone, surgery. We included trials which reported our primary outcomes: amount of PA or whether participants were engaged in PA at least six months after the intervention. A random effects meta-analysis was used to pool data across studies as risk ratios (RR), or standardised mean differences (SMDs), which we interpreted using Cohen. We used the Cochrane risk of bias tool and used GRADE to assess the certainty of the evidence. This study is registered with PROSPERO, CRD42019139008. Findings: We found 57 trials including 8548 adults and compared 71 interventions facilitating PA. Most interventions were started postoperatively and included multiple components. Compared with usual care, interventions may slightly increase the number of minutes of PA per day or week (SMD 0.17, 95% CI 0.09–0.26; 14 studies, 2172 participants; I2 = 0%), and people's engagement in PA at the study's end (RR 1.19, 95% CI 0.96–1.47; 9 studies, 882 participants; I2 = 25%); this was moderate-certainty evidence. Some studies compared two different types of interventions but it was often not feasible to combine data in analysis. The effect estimates generally indicated little difference between intervention designs and we judged all the evidence for these comparisons to be very low certainty. Thirty-six studies (63%) had low risk of selection bias for sequence generation, 27 studies (47%) had low risk of bias for allocation concealment, and 56 studies (98%) had a high risk of performance bias. For detection bias for PA outcomes, we judged 30 studies (53%) that used subjective measurement tools to have a high risk of detection bias. Interpretation: Interventions delivered in the perioperative setting, aimed at enhancing PA in the medium to long-term, may have overall benefit. However, because of imprecision in some of the findings, we could not rule out the possibility of no change in PA. Funding: National Institute for Health Research Health Services and Delivery Research programme (NIHR127879).

Abstract Background Few treatments exist for adolescents living with severe obesity. This qualitative study explored the experiences of severely obese adolescents and their families who participated in the BOB study. Methods Twelve adolescents (5 males;7 females; mean age 15 years; BMI > 3.5 s.d; puberty stage 4 +) who were engaged with the research study BOB (a non-randomised, pilot novel obesity treatment programme that involved the insertion of an intra-gastric balloon coupled with a family lifestyle behavioural support programme). Adolescents attended weekly lifestyle sessions before, during and post balloon insertion. All participants were interviewed at 3 months, (halfway through intra-gastric balloon insertion) and at 12 months follow-up (6 months post intra-gastric balloon removal, 3 months post lifestyle intervention). Results All BOB participants had exhausted all treatment options deeming this study their final option. Many alluded to feelings of desperation and referred to a sense of hope that this intervention would be effective. Family involvement and attendance within the structured sessions differed significantly. Adolescents and parents perceived support from the research study ceased when the intra-gastric balloon was removed at 6-months despite attendance post balloon removal being poor. All participants emphasised a need for further support longer term with the integration of the family a critical factor. Conclusions Further research is needed to explore the specific role families play within treatment to optimise health and wellbeing outcomes. Adolescents perspectives should be integrated within treatment to inform and improve the effectiveness of future treatment programmes for severely obese adolescents and their families.

Abstract Background To investigate the global expression profile of miRNAs, their impact on cellular signaling pathways, and their association with poor prognostic parameters in African-American (AA) patients with triple negative breast cancer (TNBC). Methods Twenty-five samples of AA TNBC patients were profiled for global miRNA expression and stratified considering three clinical-pathological parameters: tumor size, lymph node (LN), and recurrence (REC) status. Differential miRNA expression analysis was performed for each parameter, and their discriminatory power was determined by Receiver Operating Characteristic (ROC) curve analysis. KMplotter was assessed to determine the association of the miRNAs with survival, and functional enrichment analysis to determine the main affected pathways and miRNA/mRNA target interactions. Results A panel of eight, 23 and 27 miRNAs were associated with tumor size, LN, and REC status, respectively. Combined ROC analysis of two (miR-2117, and miR-378c), seven (let-7f-5p, miR-1255b-5p, miR-1268b, miR-200c-3p, miR-520d, miR-527, and miR-518a-5p), and three (miR-1200, miR-1249-3p, and miR-1271-3p) miRNAs showed a robust discriminatory power based on tumor size (AUC = 0.917), LN (AUC = 0.945) and REC (AUC = 0.981) status, respectively. Enrichment pathway analysis revealed their involvement in proteoglycans and glycan and cancer-associated pathways. Eight miRNAs with deregulated expressions in patients with large tumor size, positive LN metastasis, and recurrence were significantly associated with lower survival rates. Finally, the construction of miRNA/mRNA networks based in experimentally validated mRNA targets, revealed nodes of critical cancer genes, such as AKT1, BCL2, CDKN1A, EZR and PTEN. Conclusions Altogether, our data indicate that miRNA deregulated expression is a relevant biological factor that can be associated with the poor prognosis in TNBC of AA patients, by conferring to their TNBC cells aggressive phenotypes that are reflected in the clinical characteristics evaluated in this study.

Abstract Cancer and associated medical treatments affect patients' health-related quality of life (HRQoL) by decreasing functional dimensions of physical, social, cognitive, and emotional well-being, while increasing short and late-term symptoms. Exercise, however, is demonstrated to be a useful therapy to improve cancer patients' and survivors’ HRQoL, yet the effectiveness of high-intensity training (HIT) exercise is uncertain. This systematic review and meta-analysis aimed to analyse the effects of HIT on HRQoL dimensions in cancer patients and survivors as well as evaluate the optimal prescription of HIT. The search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) and examined Web of Science and PubMed (Medline) databases. Data were analysed utilizing Review Manager Software. Twenty-two articles were included in the systematic review and 17 in the meta-analysis. Results showed HIT improved global quality of life, physical functioning, role functioning, social functioning, cognitive functioning, fatigue, pain, dyspnea, and insomnia, compared to an inactive control group, yet no differences were found between HIT and low to moderate-intensity exercise interventions. Particular improvements in HRQoL were observed during cancer treatment and with a training duration of more than eight weeks, a frequency of 2 days/week, and a volume of at least 120 min/week, including 15 min or more of HIT. Our findings whilst encouraging, highlight the infancy of the extant evidence base for the role of HIT in the HRQoL of cancer patients and survivors.

The schizophoran superfamily Ephydroidea (Diptera: Cyclorrhapha) includes eight families, ranging from the well-known vinegar flies (Drosophilidae) and shore flies (Ephydridae), to several small, relatively unusual groups, the phylogenetic placement of which has been particularly challenging for systematists. An extraordinary diversity in life histories, feeding habits and morphology are a hallmark of fly biology, and the Ephydroidea are no exception. Extreme specialization can lead to “orphaned” taxa with no clear evidence for their phylogenetic position. To resolve relationships among a diverse sample of Ephydroidea, including the highly modified flies in the families Braulidae and Mormotomyiidae, we conducted phylogenomic sampling. Using exon capture from Anchored Hybrid Enrichment and transcriptomics to obtain 320 orthologous nuclear genes sampled for 32 species of Ephydroidea and 11 outgroups, we evaluate a new phylogenetic hypothesis for representatives of the superfamily. These data strongly support monophyly of Ephydroidea with Ephydridae as an early branching radiation and the placement of Mormotomyiidae as a family-level lineage sister to all remaining families. We confirm placement of Cryptochetidae as sister taxon to a large clade containing both Drosophilidae and Braulidae–the latter a family of honeybee ectoparasites. Our results reaffirm that sampling of both taxa and characters is critical in hyperdiverse clades and that these factors have a major influence on phylogenomic reconstruction of the history of the schizophoran fly radiation.

The schizophoran superfamily Ephydroidea (Diptera: Cyclorrhapha) includes eight families, ranging from the well-known vinegar flies (Drosophilidae) and shore flies (Ephydridae), to several small, relatively unusual groups, the phylogenetic placement of which has been particularly challenging for systematists. An extraordinary diversity in life histories, feeding habits and morphology are a hallmark of fly biology, and the Ephydroidea are no exception. Extreme specialization can lead to "orphaned" taxa with no clear evidence for their phylogenetic position. To resolve relationships among a diverse sample of Ephydroidea, including the highly modified flies in the families Braulidae and Mormotomyiidae, we conducted phylogenomic sampling. Using exon capture from Anchored Hybrid Enrichment and transcriptomics to obtain 320 orthologous nuclear genes sampled for 32 species of Ephydroidea and 11 outgroups, we evaluate a new phylogenetic hypothesis for representatives of the superfamily. These data strongly support monophyly of Ephydroidea with Ephydridae as an early branching radiation and the placement of Mormotomyiidae as a family-level lineage sister to all remaining families. We confirm placement of Cryptochetidae as sister taxon to a large clade containing both Drosophilidae and Braulidae-the latter a family of honeybee ectoparasites. Our results reaffirm that sampling of both taxa and characters is critical in hyperdiverse clades and that these factors have a major influence on phylogenomic reconstruction of the history of the schizophoran fly radiation.

Anaplasmosis, caused by infection with bacteria of the genus Anaplasma, is an important veterinary and zoonotic disease. Transmission by ticks has been characterized but little is known about non-tick vectors of livestock anaplasmosis. This study investigated the presence of Anaplasma spp. in camels in northern Kenya and whether the hematophagous camel ked, Hippobosca camelina, acts as a vector. Camels (n = 976) and > 10,000 keds were sampled over a three-year study period and the presence of Anaplasma species was determined by PCR-based assays targeting the Anaplasmataceae 16S rRNA gene. Camels were infected by a single species of Anaplasma, 'Candidatus Anaplasma camelii', with infection rates ranging from 63-78% during the dry (September 2017), wet (June-July 2018), and late wet seasons (July-August 2019). 10-29% of camel keds harbored 'Ca. Anaplasma camelii' acquired from infected camels during blood feeding. We determined that Anaplasma-positive camel keds could transmit 'Ca. Anaplasma camelii' to mice and rabbits via blood-feeding. We show competence in pathogen transmission and subsequent infection in mice and rabbits by microscopic observation in blood smears and by PCR. Transmission of 'Ca. Anaplasma camelii' to mice (8-47%) and rabbits (25%) occurred readily after ked bites. Hence, we demonstrate, for the first time, the potential of H. camelina as a vector of anaplasmosis. This key finding provides the rationale for establishing ked control programmes for improvement of livestock and human health.

Abstract Background The National Health Service (NHS) seems appropriately placed to be an exemplar employer in providing effective and proactive workplace health and wellbeing services for its staff. However, NHS staff sickness absence costs an estimated £2.4 billion. Evidence suggests staff health and wellbeing services delivered in the NHS can improve health, productivity and sickness absence and yet the adoption of these services remains a challenge, with few examples nationally. This research aimed to explore the perceptions of NHS senior leaders and health and wellbeing practitioners regarding barriers and facilitators to implementing workplace health and wellbeing services for staff in the NHS. Methods Semi-structured interviews were conducted with NHS staff, consisting of four senior leaders, four heads of department and three health and wellbeing practitioners in one region of the UK. Interviews were transcribed verbatim and analysed using thematic analysis. Results Themes describe the experience of delivering workplace health and wellbeing services in the NHS, and barriers and facilitators to implementation from senior decision makers. Barriers to implementation of services include; a busy and pressurised environment, financial constraints and reluctance to invest in staff health and wellbeing. Barriers to staff engagement were also reported and include difficulty of access to health and wellbeing services and lack of time. Initiating services were facilitated by financial incentives, a supportive organisational structure and culture that takes a preventative, rather than reactive, approach to staff health and wellbeing. Facilitators to implementing health and wellbeing services include a coherent, strategic approach to implementation, effective communication and advertisement, being creative and innovative with resources and conducting a needs analysis and evaluation before, during and after implementation. Conclusions Barriers to the successful initiation and implementation of health and wellbeing services in the NHS are numerous and range from front-line logistical issues with implementation to high-level strategic and financial constraints. Adopting a strategic and needs-led approach to implementation and ensuring thorough staff engagement are amongst a number of factors that facilitate implementation and help overcome barriers to initiation of wellbeing programmes in the NHS. There is a need for a culture that supports staff health and wellbeing in the NHS.

The family Ismaridae Thomson, 1858 is reported from the Afrotropical region for the first time. A total of 15 species are recognised, 14 of which are described as new: Ismarus africanus sp. n. from Cameroon, Kenya, Malawi, South Africa; I. apertus sp. n. from Kenya; I. bicolor sp. n. from Cameroon, Kenya; I. goodrichi sp. n. from Kenya; I. kakamegensis sp. n. from Kenya; I. kenyensis sp. n. from Kenya; I. laevigatus sp. n. from South Africa; I. madagascariensis sp. n. from Madagascar; I. minutus sp. n. from Kenya, Malawi, Zimbabwe; I. nigrofasciatus sp. n. from Malawi, Uganda; I. notaulicus sp. n. from Kenya; I. rawlinsi sp. n. from Kenya, Malawi; I. steineri sp. n. from Madagascar; I. watshami sp. n. from Botswana, Malawi, South Africa, Zimbabwe. Ismarus halidayi Förster is reported for continental Africa from South Africa (new record). We provide an identification key to all species in Afrotropical region.

The promotion of edible insects, including saturniid caterpillars as potential food source is widely gaining momentum. They are adequately rich in nutrients such as proteins, amino acids, fatty acids, and micronutrients. Despite saturniids being a traditional food source with economic benefits, information on their diversity, host plants and their potential distribution in Africa are lacking, which this study seeks to address. Edible saturniids and their host plants were characterized using specific primers (LepF1/LepR1 and 3F_KIM_F/1R_KIM_R, respectively). Maximum entropy (MaxENT) and GARP (genetic algorithm for ruleset production) models were used to characterize the potential distribution of commonly consumed saturniids under current and future climate scenarios. Seven species of saturniids were recorded from 11 host plants in Kenya: Gonimbrasia zambesina, Gonimbrasia krucki, Bunaea alcinoe, Gonimbrasia cocaulti, Gonimbrasia belina, Gynanisa nigra and Cirina forda. Two morphotypes of G. zambesina and B. alcinoe were recorded. These saturniid caterpillars occur twice a year except for G. cocaulti. Predictive models revealed that tropical and subtropical regions were potentially suitable for B. alcinoe and C. forda. The information generated from this study would be important to guide conservation efforts and their sustainable utilization as food in Africa.

The species Hedychridium buffingtoni Kimsey & Copeland, sp. n. is described from two male specimens collected in Kasaala, Kenya. They are distinguished from other species of Hedychridium by the strongly transversely carinate metasomal terga II and III, edentate apical rim of tergum III, strongly lobed propodeal tooth, ecarinate frons and darkly pigmented cuspis.

This paper describes five new Ceratitis species from the eastern and southern parts of the Afrotropical Region: C. (Pterandrus) quilicii De Meyer, Mwatawala & Virgilio sp. nov.; C. (Ceratalaspis) pallidula De Meyer, Mwatawala & Virgilio sp. nov.; C. (Ceratalaspis) taitaensis De Meyer & Copeland sp. nov.; C. (Ceratalaspis) sawahilensis De Meyer & Virgilio sp. nov.; and C. (Ceratalaspis) flavipennata De Meyer & Virgilio sp. nov. Their relationships with closely allied species within their respective subgenera are discussed where appropriate, and diagnostic characters are given. DNA barcodes are provided for all new species. In addition, the hitherto unknown male of C. (Pardalaspis) serrata De Meyer, 1996 is described, based on material collected in the Democratic Republic of Congo. Recognition of these new species and sexes is the result of an integrative approach using morphological characters and DNA data.

We revise two relatively rare ensign wasp genera, whose species are restricted to Sub-Saharan Africa: Afrevania and Trissevania. Afrevania longipetiolata sp. nov., Trissevania heatherae sp. nov., T. hugoi sp. nov., T. mrimaensis sp. nov. and T. slideri sp. nov. are described, males and females of T. anemotis and Afrevania leroyi are redescribed, and an identification key for Trissevaniini is provided. We argue that Trissevania mrimaensis sp. nov. and T. heatherae sp. nov. populations are vulnerable, given their limited distributions and threats from mining activities in Kenya. We hypothesize that these taxa together comprise a monophyletic lineage, Trissevaniini, tr. nov., the members of which share the ability to fold their fore wings along two intersecting fold lines. Although wing folding of this type has been described for the hind wing of some insects four-plane wing folding of the fore wing has never been documented. The wing folding mechanism and the pattern of wing folds of Trissevaniini is shared only with some cockroach species (Blattodea). It is an interesting coincidence that all evaniids are predators of cockroach eggs. The major wing fold lines of Trissevaniini likely are not homologous to any known longitudinal anatomical structures on the wings of other Evaniidae. Members of the new tribe share the presence of a coupling mechanism between the fore wing and the mesosoma that is composed of a setal patch on the mesosoma and the retinaculum of the fore wing. While the setal patch is an evolutionary novelty, the retinaculum, which originally evolved to facilitate fore and hind wing coupling in Hymenoptera, exemplifies morphological exaptation. We also refine and clarify the Semantic Phenotype approach used in previous taxonomic revisions and explore the consequences of merging new with existing data. The way that semantic statements are formulated can evolve in parallel, alongside improvements to the ontologies themselves.