A longitudinal study combining the Double Diamond framework and Behavior Change Wheel to co-create a sedentary behavior intervention in police control rooms.

BACKGROUND: Police work can be sedentary and stressful, negatively impacting health and wellbeing. In a novel co-creation approach, we used the Behavior Change Wheel (BCW) and Double Diamond (DD) design framework to guide the collaborative design and development of a sedentary behavior intervention in the control rooms of two British police forces. METHODS: Multiple stakeholders participated in four phases of research. In Phase 1, a literature review, focus groups (n = 20) and interviews (n = 10) were conducted to 'discover' the relationship between physical activity and wellbeing in the police. In Phase 2, a steering group consolidated Phase 1 findings to 'define' a specific behavior for intervention. Phases 3 and 4 'developed' the intervention across six workshops with control room workers and six steering group workshops. RESULTS: The co-creation process identified contextual sedentary behavior as the target behavior, driven by behavioral regulation, social influence and social norms. The sedentary behavior intervention targeted these drivers and aimed to engage control room workers in short bursts of physical activity throughout their shifts. Key intervention features targeted involvement of staff in decision-making and embedding physical activity into work practices. CONCLUSIONS: The BCW and DD can be combined to co-create evidence-based and participant-informed interventions and translate science into action.

Outcomes reported in randomised trials of surgical prehabilitation: a scoping review.

BACKGROUND: Heterogeneity of reported outcomes can impact the certainty of evidence for prehabilitation. The objective of this scoping review was to systematically map outcomes and assessment tools used in trials of surgical prehabilitation. METHODS: MEDLINE, EMBASE, PsychInfo, Web of Science, CINAHL, and Cochrane were searched in February 2023. Randomised controlled trials of unimodal or multimodal prehabilitation interventions (nutrition, exercise, psychological support) lasting at least 7 days in adults undergoing elective surgery were included. Reported outcomes were classified according to the International Society for Pharmacoeconomics and Outcomes Research framework. RESULTS: We included 76 trials, mostly focused on abdominal or orthopaedic surgeries. A total of 50 different outcomes were identified, measured using 184 outcome assessment tools. Observer-reported outcomes were collected in 86% of trials (n=65), with hospital length of stay being most common. Performance outcomes were reported in 80% of trials (n=61), most commonly as exercise capacity assessed by cardiopulmonary exercise testing. Clinician-reported outcomes were included in 78% (n=59) of trials and most frequently included postoperative complications with Clavien-Dindo classification. Patient-reported outcomes were reported in 76% (n=58) of trials, with health-related quality of life using the 36- or 12-Item Short Form Survey being most prevalent. Biomarker outcomes were reported in 16% of trials (n=12) most commonly using inflammatory markers assessed with C-reactive protein. CONCLUSIONS: There is substantial heterogeneity in the reporting of outcomes and assessment tools across surgical prehabilitation trials. Identification of meaningful outcomes, and agreement on appropriate assessment tools, could inform the development of a prehabilitation core outcomes set to harmonise outcome reporting and facilitate meta-analyses.

The Development of a Multi-Modal Cancer Rehabilitation (Including Prehabilitation) Service in Sheffield, UK: Designing the Active Together Service.

Cancer patients undergoing major interventions face numerous challenges, including the adverse effects of cancer and the side effects of treatment. Cancer rehabilitation is vital in ensuring cancer patients have the support they need to maximise treatment outcomes and minimise treatment-related side effects and symptoms. The Active Together service is a multi-modal rehabilitation service designed to address critical support gaps for cancer patients. The service is located and provided in Sheffield, UK, an area with higher cancer incidence and mortality rates than the national average. The service aligns with local and regional cancer care objectives and aims to improve the clinical and quality-of-life outcomes of cancer patients by using lifestyle behaviour-change techniques to address their physical, nutritional, and psychological needs. This paper describes the design and initial implementation of the Active Together service, highlighting its potential to support and benefit cancer patients.

Towards a common definition of surgical prehabilitation: a scoping review of randomised trials.

BACKGROUND: There is no universally accepted definition for surgical prehabilitation. The objectives of this scoping review were to (1) identify how surgical prehabilitation is defined across randomised controlled trials and (2) propose a common definition. METHODS: The final search was conducted in February 2023 using MEDLINE, Embase, PsycINFO, Web of Science, CINAHL, and Cochrane. We included randomised controlled trials (RCTs) of unimodal or multimodal prehabilitation interventions (nutrition, exercise, and psychological support) lasting at least 7 days in adults undergoing elective surgery. Qualitative data were analysed using summative content analysis. RESULTS: We identified 76 prehabilitation trials of patients undergoing abdominal (n=26, 34%), orthopaedic (n=20, 26%), thoracic (n=14, 18%), cardiac (n=7, 9%), spinal (n=4, 5%), and other (n=5, 7%) surgeries. Surgical prehabilitation was explicitly defined in more than half of these RCTs (n=42, 55%). Our findings consolidated the following definition: 'Prehabilitation is a process from diagnosis to surgery, consisting of one or more preoperative interventions of exercise, nutrition, psychological strategies and respiratory training, that aims to enhance functional capacity and physiological reserve to allow patients to withstand surgical stressors, improve postoperative outcomes, and facilitate recovery.' CONCLUSIONS: A common definition is the first step towards standardisation, which is needed to guide future high-quality research and advance the field of prehabilitation. The proposed definition should be further evaluated by international stakeholders to ensure that it is comprehensive and globally accepted.

International consensus is needed on a core outcome set to advance the evidence of best practice in cancer prehabilitation services and research.

Prehabilitation aims to optimise patients' physical and psychological status before treatment. The types of outcomes measured to assess the impact of prehabilitation interventions vary across clinical research and service evaluation, limiting the ability to compare between studies and services and to pool data. An international workshop involving academic and clinical experts in cancer prehabilitation was convened in May 2022 at Sheffield Hallam University's Advanced Wellbeing Research Centre, England. The workshop substantiated calls for a core outcome set to advance knowledge and understanding of best practice in cancer prehabilitation and to develop national and international databases to assess outcomes at a population level.

Tackling physical inactivity and inequalities: implementing a whole systems approach to transform community provision for disabled people and people with long-term health conditions.

BACKGROUND: Physical inactivity is a global public health priority. There are known health and well-being consequences of being inactive, and the benefits of being physically active are well established. However, there are persistent inequalities when it comes to how physically active people are, with disabled people, people living with long-term health conditions, and people residing in areas of socio-economic deprivation being particularly affected. Methods such as whole system approaches (WSAs), which are dynamic, multifaceted, and engage all relevant stakeholders, have gained momentum as an approach to address such complex public health problems. However, evidence relating to the implementation of WSAs to address physical inactivity is lacking. The aim of the Prevention and Enablement Model (PEM) was to take a whole system approach in Essex to encourage and support disabled people and/or individuals living with long-term health conditions to be more active, happier, and to live more independently. METHODS: The aim of this study was to explore the enablers, challenges, and reflections associated with the process of designing and implementing the PEM. Semi-structured interviews (n = 12) were used to collect data from people involved in the PEM's design, implementation and/or delivery. Data was analysed using Braun and Clarke's reflexive thematic analysis. RESULTS: Four themes were identified: (1) Working collaboratively: Specific enablers of time and space were identified as important in the planning and implementation of a WSA (2) Leadership and planning: Distributed and flexible leadership was identified as central to successful implementation (3) Re-orientating practice: Highlighted the transformative potential of a whole system approach and how it contrasts with conventional work practices, and (4) Reflection and learning: Informing ongoing refinements and further implementation of successful system change. CONCLUSIONS: These findings highlight the challenge and complexity of implementing a WSA that involves diverse stakeholders from across adult social care, the NHS, and the third sector. Several important enablers are identified, such as leadership and planning, and the challenges and discomfort that can arise whilst changing systems. Ongoing efforts are required to ensure that different elements of the system collaborate effectively to address inequalities in physical activity participation, through the implementation of a WSA.

Validating Indigenous Farmers' Practice in the Management of the Fall Armyworm Spodoptera frugiperda (J. E. Smith) in Maize Cropping Systems in Africa.

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.

Supporting physical activity through co-production in people with severe mental ill health (SPACES): protocol for a randomised controlled feasibility trial.

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.

The Chalcidoidea bush of life: evolutionary history of a massive radiation of minute wasps.

Chalcidoidea are mostly parasitoid wasps that include as many as 500 000 estimated species. Capturing phylogenetic signal from such a massive radiation can be daunting. Chalcidoidea is an excellent example of a hyperdiverse group that has remained recalcitrant to phylogenetic resolution. We combined 1007 exons obtained with Anchored Hybrid Enrichment with 1048 ultra-conserved elements (UCEs) for 433 taxa including all extant families, >95% of all subfamilies, and 356 genera chosen to represent the vast diversity of the superfamily. Going back and forth between the molecular results and our collective knowledge of morphology and biology, we detected bias in the analyses that was driven by the saturation of nucleotide data. Our final results are based on a concatenated analysis of the least saturated exons and UCE datasets (2054 loci, 284 106 sites). Our analyses support an expected sister relationship with Mymarommatoidea. Seven previously recognized families were not monophyletic, so support for a new classification is discussed. Natural history in some cases would appear to be more informative than morphology, as illustrated by the elucidation of a clade of plant gall associates and a clade of taxa with planidial first-instar larvae. The phylogeny suggests a transition from smaller soft-bodied wasps to larger and more heavily sclerotized wasps, with egg parasitism as potentially ancestral for the entire superfamily. Deep divergences in Chalcidoidea coincide with an increase in insect families in the fossil record, and an early shift to phytophagy corresponds with the beginning of the "Angiosperm Terrestrial Revolution". Our dating analyses suggest a middle Jurassic origin of 174 Ma (167.3-180.5 Ma) and a crown age of 162.2 Ma (153.9-169.8 Ma) for Chalcidoidea. During the Cretaceous, Chalcidoidea may have undergone a rapid radiation in southern Gondwana with subsequent dispersals to the Northern Hemisphere. This scenario is discussed with regard to knowledge about the host taxa of chalcid wasps, their fossil record and Earth's palaeogeographic history.

Deregulated miRNA Expression in Triple-Negative Breast Cancer of Ancestral Genomic-Characterized Latina Patients.

Among patients with triple-negative breast cancer (TNBC), several studies have suggested that deregulated microRNA (miRNA) expression may be associated with a more aggressive phenotype. Although tumor molecular signatures may be race- and/or ethnicity-specific, there is limited information on the molecular profiles in women with TNBC of Hispanic and Latin American ancestry. We simultaneously profiled TNBC biopsies for the genome-wide copy number and miRNA global expression from 28 Latina women and identified a panel of 28 miRNAs associated with copy number alterations (CNAs). Four selected miRNAs (miR-141-3p, miR-150-5p, miR-182-5p, and miR-661) were validated in a subset of tumor and adjacent non-tumor tissue samples, with miR-182-5p being the most discriminatory among tissue groups (AUC value > 0.8). MiR-141-3p up-regulation was associated with increased cancer recurrence; miR-661 down-regulation with larger tumor size; and down-regulation of miR-150-5p with larger tumor size, high p53 expression, increased cancer recurrence, presence of distant metastasis, and deceased status. This study reinforces the importance of integration analysis of CNAs and miRNAs in TNBC, allowing for the identification of interactions among molecular mechanisms. Additionally, this study emphasizes the significance of considering the patients ancestral background when examining TNBC, as it can influence the relationship between intrinsic tumor molecular characteristics and clinical manifestations of the disease.

Development of assays to support identification and characterization of modulators of DExH-box helicase DHX9.

DHX9 is a DExH-box RNA helicase that utilizes hydrolysis of all four nucleotide triphosphates (NTPs) to power cycles of 3' to 5' directional movement to resolve and/or unwind double stranded RNA, DNA, and RNA/DNA hybrids, R-loops, triplex-DNA and G-quadraplexes. DHX9 activity is important for both viral amplification and maintaining genomic stability in cancer cells; therefore, it is a therapeutic target of interest for drug discovery efforts. Biochemical assays measuring ATP hydrolysis and oligonucleotide unwinding for DHX9 have been developed and characterized, and these assays can support high-throughput compound screening efforts under balanced conditions. Assay development efforts revealed DHX9 can use double stranded RNA with 18-mer poly(U) 3' overhangs and as well as significantly shorter overhangs at the 5' or 3' end as substrates. The enzymatic assays are augmented by a robust SPR assay for compound validation. A mechanism-derived inhibitor, GTPγS, was characterized as part of the validation of these assays and a crystal structure of GDP bound to cat DHX9 has been solved. In addition to enabling drug discovery efforts for DHX9, these assays may be extrapolated to other RNA helicases providing a valuable toolkit for this important target class.

Cyclin A2 and Ki-67 proliferation markers could be used to identify tumors with poor prognosis in African American women with breast cancer.

Background: Diagnosed invasive breast carcinomas in African American patients are more aggressive compared with those in Caucasian patients and diagnosed at later stages of the disease with higher grade tumors. Despite advances in breast cancer systemic treatment, new prognostic and predictive biomarkers are still needed. Therefore, potential biomarkers were chosen to correlate with different subtypes, recurrence, and survival of invasive breast cancer in a cohort of African American women. Methods: Eight protein biomarkers (ER, PR, HER2, Cyclin A2, Cytokeratin 5, Vimentin, Bcl2, and Ki-67) were evaluated using tissue microarrays (TMAs) and immunohistochemistry (IHC). The IHC results from TMAs were analyzed by both supervised and unsupervised clustering methods. The predictive clusters for the supervised and unsupervised methods were compared for agreement with the empirical classification. Kappa values were used to determine the overall percent correct clusters and agreement between specific clusters. Chi-square statistics was used to examine the association between hierarchical and multinomial logistic clustering methods. Results: Five subtypes of breast tumors with distinct protein expression patterns were identified among the studied 166 breast tumors. Luminal B tumors have been distinguished from luminal A tumors by staining for cell cycle proteins Cyclin A2 and Ki-67, which promote cell proliferation. Forty-nine percent were stained positive for Cyclin A2, 39.2% positive for Ki-67, and 37% positive for both Cyclin A2 and Ki-67. The age of patients did not show any significant effect whether five (p-value= 0.576) or eight (p-value= 0.605) biomarkers were used, which indicating that age did not have any influence on the classification of the subtypes. Ninety percent of the thirty triple negative tumors were positive for Cyclin A2 or Ki-67 or both. Six-year overall survival was better for luminal A tumors (76%) than luminal B tumors (71%). Likewise, six-year relapse-free survival was better for luminal A tumors (76%) than luminal B tumors (29%). Conclusion: Discovery of molecular markers such as Cyclin A2 and Ki-67, and subtypes that are most prevalent in African Americans could lead to a better understanding of the factors contributing to higher morbidity and mortality in this group and to aid in decision-making to offer earlier treatment.

The importance of binding kinetics and drug-target residence time in pharmacology.

A dominant assumption in pharmacology throughout the 20th century has been that in vivo target occupancy-and attendant pharmacodynamics-depends on the systemic concentration of drug relative to the equilibrium dissociation constant for the drug-target complex. In turn, the duration of pharmacodynamics is temporally linked to the systemic pharmacokinetics of the drug. Yet, there are many examples of drugs for which pharmacodynamic effect endures long after the systemic concentration of a drug has waned to (equilibrium) insignificant levels. To reconcile such data, the drug-target residence time model was formulated, positing that it is the lifetime (or residence time) of the binary drug-target complex, and not its equilibrium affinity per se, that determines the extent and duration of drug pharmacodynamics. Here, we review this model, its evolution over time, and its applications to natural ligand-macromolecule biology and synthetic drug-target pharmacology.

Effectiveness of the perioperative encounter in promoting regular exercise and physical activity: a systematic review and meta-analysis.

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).

Physical Activity in Adults with Schizophrenia and Bipolar Disorder: A Large Cross-Sectional Survey Exploring Patterns, Preferences, Barriers, and Motivating Factors.

Adults with severe mental ill health may have specific attitudes toward physical activity. To inform intervention development, we conducted a survey to assess the physical activity patterns, preferences, barriers, and motivations of adults with severe mental ill health living in the community. Data were summarised using descriptive statistics, and logistic regressions were used to explore relationships between physical activity status and participant characteristics. Five-hundred and twenty-nine participants (58% male, mean age 49.3 years) completed the survey. Large numbers were insufficiently active and excessively sedentary. Self-reported levels of physical activity below that recommended in national guidelines were associated with professional inactivity, consumption of fewer than five portions of fruit and vegetables per day, older age, and poor mental health. Participants indicated a preference for low-intensity activities and physical activity that they can do on their own, at their own time and pace, and close to home. The most commonly endorsed source of support was social support from family and friends. Common motivations included improving mental health, physical fitness, and energy levels. However, poor mental and physical health and being too tired were also common barriers. These findings can inform the development of physical activity interventions for this group of people.

Physical Inactivity Levels of European Adolescents in 2002, 2005, 2013, and 2017.

Sport and Physical Activity (PA) Special Eurobarometer surveys may inform of the physical inactivity (PIA) levels in the European Union (EU). This study aimed to analyse the PIA levels of EU adolescents (15-17 years) in four time points, according to gender. The data were from 2002, 2005, 20013, and 2017 Special Eurobarometers. Adolescents were categorised as "Inactive" when performing less than 60 min/day of moderate to vigorous PA on average. A χ2 test was used to compare the levels of PIA between survey years. PIA levels between gender were analysed using a Z-score test for two population proportions. PIA levels ranged from 67.2% for boys (59.4% to 71.5%;) to 76.8% for girls (76.0% to 83.4) across the time points. Adjusted standardised residuals revealed a decrease in the observed levels versus the expected for 2005 (whole sample: -4.2; boys: -3.3) and an increase for 2013 (whole sample: +2.9; boys: +2.5). Boys presented lower PIA levels than girls in all years (p ≤ 0.003), but descriptively, the difference progressively decreased (from 18.4% to 11.8%). No significant reductions in PIA levels were observed between 2002 and 2017, and girls reported consistently higher levels of PIA than boys.

Dihydromyricetin Protects Against Salsolinol-Induced Toxicity in Dopaminergic Cell Line: Implication for Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease associated with loss of dopaminergic neurons in the substantia nigra pars compacta. Although aging is the primary cause, environmental and genetic factors have also been implicated in its etiology. In fact, the sporadic nature of PD (i.e., unknown etiology) renders the uncovering of the exact pathogenic mechanism(s) or development of effective pharmacotherapies challenging. In search of novel neuroprotectants, we showed that butyrate (BUT), a short-chain fatty acid, protects against salsolinol (SALS)-induced toxicity in human neuroblastoma-derived SH-SY5Y cells, which are considered an in-vitro model of PD. Dihydromyricetin (DHM), a flavonoid derived from Asian medicinal plant, has also shown effectiveness against oxidative damage and neuroinflammation, hallmarks of neurodegenerative diseases. Here we show that pretreatment of SH-SY5Y cells with DHM concentration-dependently prevented SALS-induced toxicity and that a combination of DHM and BUT resulted in a synergistic protection. The effects of both DHM and BUT in turn could be completely blocked by flumazenil (FLU), a GABAA antagonist acting at benzodiazepine receptor site, and by bicuculline (BIC), a GABAA antagonist acting at orthosteric site. Beta-hydroxybutyrate (BHB), a free fatty acid 3 (FA3) receptor antagonist, also fully blocked the protective effect of DHM. BHB was shown previously to only partially block the protective effect of BUT. Thus, there are some overlaps and some distinct differences in protective mechanisms of DHM and BUT against SALS-induced toxicity. It is suggested that a combination of DHM and BUT may have therapeutic potential in PD. However, further in-vivo verifications are necessary.

Abundance, diversity and richness of natural enemies of the fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), in Zambia.

The fall armyworm (FAW), Spodoptera frugiperda, an invasive pest originating from the Americas is a serious pest threatening cereal production and food security in Zambia. We studied the prevalence and abundance of natural enemies of FAW in three Agroecological regions (AERs I, II, and III) to identify those that could potentially serve as bio-control agents. Sampling of FAW parasitoids and predators was done along trunk roads at intervals of 10 km. Molecular sequence analysis and morphological characterization were used to identify natural enemies. Over 11 species of FAW natural enemies, including egg, egg-larval, and larval parasitoids, and predators, were identified in Zambia. The mean number of natural enemies and species richness was higher in AER I and IIa. Consequently, egg parasitism was highest in those two regions, at 24.5% and 12.2%, respectively. Larvae parasitism was highest in AER I (4.8%) and AER III (1.9), although no significant differences were observed. The most abundant and widely distributed parasitoid was Drino sp. (Diptera: Tachinidae), while Rhynocoris segmentarius (Germar) (Hemiptera: Reduviidae) and Belanogaster sp. (Hymenoptera: Vespidae) were the most prevalent predators. Our study reveals the presence of two natural enemies belonging to the genus Tiphia and Micromeriella, uncommon to FAW. Significant differences in the number of parasitoids were observed in polycropping, with the highest recovery of 12 ± 10% from maize + cowpeas + pumpkin and watermelon mixed cropping. The higher the rainfall, the lower the number of natural enemies recorded. Variations in rainfall patterns which affect FAW availability, cropping systems and the three AERs may explain natural enemies' species diversity in Zambia. The information provided in this study can aid the development of a national biological control programme for sustainable management of fall armyworm.

African Platyplectrus Ferrire (Hymenoptera: Eulophidae) from Kenya, with description of nine new species.

Eleven species of Platyplectrus have been recorded from the Afrotropical region. Ch. Ferrire described nine species in 1941: two of them as Platyplectrus (P. capensis and P. ornatus) and seven under Euplectromorpha (Platyplectrus ausensis, P. brevicornis, P. kiambuensis, P. obscuratus, P. nitidiceps, P. striolata and Euplectromorpha variegata (not synonymized until the present paper)). Subsequently, P. meruensis was described by Delucchi (1962) and P. desertus by Yefremova (2008). To date, only one species, P. kiambuensis, has been recorded from Kenya. Recently, a wide-ranging survey and inventory project in Kenya raised this number to 18 species, nine of which are new and described herein: Platyplectrus albiclavatus sp. nov., P. kayaensis sp. nov., P. marenjeensis sp. nov., P. mrimaensis sp. nov., P. ngangaoensis sp. nov., P. nyambeneensis sp. nov., P. nyanzaensis sp. nov., P. pseudoornatus sp. nov., and P. pyrrhomaculatus sp. nov. Three species are redescribed: two for both sexes (P. meruensis, P. obscuratus) and one for females (P. ornatus). A new combination is proposed for Platyplectrus striolatus (Ferrire) from Euplectromorpha striolata Ferrire, 1941, and Euplectromorpha variegata Ferrire, 1941 is synonymized with Platyplectrus nigroflaveatus Yefremova, and the female is redescribed. A key to the genus Platyplectrus is provided for the 18 species found in Kenya.

Phylogenetic resolution of the fly superfamily Ephydroidea-Molecular systematics of the enigmatic and diverse relatives of Drosophilidae.

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.