From bile acids to melancholia.

In this issue of Neuron, Li, Zhang, et al.1 find that the bile acid receptor TGR5 in the lateral hypothalamus influences neuronal dynamics underlying stress-induced depression-like behaviors. Inhibition of these neurons produces antidepressant-like effects through a circuit that includes hippocampal CA3 and dorsolateral septum, revealing a novel potential therapeutic for depression.

A blood test to monitor bee health across a European network of agricultural sites of different land-use by MALDI BeeTyping mass spectrometry.

There are substantial concerns about impaired honey bee health and colony losses due to several poorly understood factors. We used MALDI profiling (MALDI BeeTyping®) analysis to investigate how some environmental and management factors under field conditions across Europe affected the honey bee haemolymph peptidome (all peptides in the circulatory fluid), as a profile of molecular markers representing the immune status of Apis mellifera. Honey bees were exposed to a range of environmental stressors in 128 agricultural sites across eight European countries in four biogeographic zones, with each country contributing eight sites each for two different cropping systems: oilseed rape (OSR) and apple (APP). The full haemolymph peptide profiles, including the presence and levels of three key immunity markers, namely the antimicrobial peptides (AMPs) Apidaecin, Abaecin and Defensin-1, allowed the honey bee responses to environmental variables to be discriminated by country, crop type and site. When considering just the AMPs, it was not possible to distinguish between countries by the prevalence of each AMP in the samples. However, it was possible to discriminate between countries on the amounts of the AMPs, with the Swedish samples in particular expressing high amounts of all AMPs. A machine learning model was developed to discriminate the haemolymphs of bees from APP and OSR sites. The model was 90.6 % accurate in identifying the crop type from the samples used to build the model. Overall, MALDI BeeTyping® of bee haemolymph represents a promising and cost-effective "blood test" for simultaneously monitoring dozens of peptide markers affected by environmental stressors at the landscape scale, thus providing policymakers with new diagnostic and regulatory tools for monitoring bee health.

Small fibre neuropathy in Fabry disease: a human-derived neuronal in vitro disease model and pilot data.

Acral burning pain triggered by fever, thermal hyposensitivity and skin denervation are hallmarks of small fibre neuropathy in Fabry disease, a life-threatening X-linked lysosomal storage disorder. Variants in the gene encoding alpha-galactosidase A may lead to impaired enzyme activity with cellular accumulation of globotriaosylceramide. To study the underlying pathomechanism of Fabry-associated small fibre neuropathy, we generated a neuronal in vitro disease model using patient-derived induced pluripotent stem cells from three Fabry patients and one healthy control. We further generated an isogenic control line via gene editing. We subjected induced pluripotent stem cells to targeted peripheral neuronal differentiation and observed intra-lysosomal globotriaosylceramide accumulations in somas and neurites of Fabry sensory neurons using super-resolution microscopy. At functional level, patch-clamp analysis revealed a hyperpolarizing shift of voltage-gated sodium channel steady-state inactivation kinetics in isogenic control neurons compared with healthy control neurons (P < 0.001). Moreover, we demonstrate a drastic increase in Fabry sensory neuron calcium levels at 39°C mimicking clinical fever (P < 0.001). This pathophysiological phenotype was accompanied by thinning of neurite calibres in sensory neurons differentiated from induced pluripotent stem cells derived from Fabry patients compared with healthy control cells (P < 0.001). Linear-nonlinear cascade models fit to spiking responses revealed that Fabry cell lines exhibit altered single neuron encoding properties relative to control. We further observed mitochondrial aggregation at sphingolipid accumulations within Fabry sensory neurites utilizing a click chemistry approach together with mitochondrial dysmorphism compared with healthy control cells. We pioneer pilot insights into the cellular mechanisms contributing to pain, thermal hyposensitivity and denervation in Fabry small fibre neuropathy and pave the way for further mechanistic in vitro studies in Fabry disease and the development of novel treatment approaches.

Novel indices reveal that pollinator exposure to pesticides varies across biological compartments and crop surroundings.

Declines in insect pollinators have been linked to a range of causative factors such as disease, loss of habitats, the quality and availability of food, and exposure to pesticides. Here, we analysed an extensive dataset generated from pesticide screening of foraging insects, pollen-nectar stores/beebread, pollen and ingested nectar across three species of bees collected at 128 European sites set in two types of crop. In this paper, we aimed to (i) derive a new index to summarise key aspects of complex pesticide exposure data and (ii) understand the links between pesticide exposures depicted by the different matrices, bee species and apple orchards versus oilseed rape crops. We found that summary indices were highly correlated with the number of pesticides detected in the related matrix but not with which pesticides were present. Matrices collected from apple orchards generally contained a higher number of pesticides (7.6 pesticides per site) than matrices from sites collected from oilseed rape crops (3.5 pesticides), with fungicides being highly represented in apple crops. A greater number of pesticides were found in pollen-nectar stores/beebread and pollen matrices compared with nectar and bee body matrices. Our results show that for a complete assessment of pollinator pesticide exposure, it is necessary to consider several different exposure routes and multiple species of bees across different agricultural systems.

Genetic variants of unknown significance in alpha-galactosidase A: Cellular delineation from Fabry disease.

Fabry disease (FD) is an X-linked multiorgan disorder caused by variants in the alpha-galactosidase A gene (GLA). Depending on the variant, disease phenotypes range from benign to life-threatening. More than 1000 GLA variants are known, but a link between genotype and phenotype in FD has not yet been established for all. p.A143T, p.D313Y, and p.S126G are frequent examples of variants of unknown significance (VUS). We have investigated the potential pathogenicity of these VUS combining clinical data with data obtained in human cellular in vitro systems. We have analyzed four different male subject-derived cell types for alpha-galactosidase A enzyme (GLA) activity and intracellular Gb3 load. Additionally, Gb3 load in skin tissue as well as clinical data were studied for correlates of disease manifestations. A reduction of GLA activity was observed in cells carrying p.A143T compared with controls (p < 0.05). In cells carrying the p.D313Y variant, a reduced GLA activity was found only in endothelial cells (p < 0.01) compared with controls. No pathological changes were observed in cells carrying the p.S126G variant. None of the VUS investigated caused intracellular Gb3 accumulation in any cell type. Our data of aberrant GLA activity in cells of p.A143T hemizygotes and overall normal cellular phenotypes in cells of p.D313Y and p.S126G hemizygotes contribute a basic science perspective to the clinically highly relevant discussion on VUS in GLA.

Perceived Need for a Faith-Based Trauma-Focused Treatment in a Sample of Forcibly Displaced Muslims.

Forcibly displaced Muslims, including refugees, internally displaced persons, and asylum seekers who have fled their homes to escape violence, conflict, and persecution, often have inequitable access to quality mental health services, despite substantial trauma exposure and high rates of posttraumatic stress disorder (PTSD). Understanding factors associated with domains of perceived need (i.e., community, individual, friends/family) for culturally-responsive, trauma-focused mental health interventions among forcibly displaced Muslims may provide insight into those most likely to seek psychological treatment. A sample of 108 forcibly displaced Muslims endorsed moderate to high perceived need across all three domains for a trauma healing group tailored for Muslim refugees. PTSD severity related to perceived individual need, regardless of locus of displacement. Among participants with minimal PTSD symptoms, those who were externally displaced had higher perceived community and friends or family need than those who were internally displaced. Findings highlight a need for culturally responsive, trauma-focused mental health services to facilitate access to mental health care for forcibly displaced Muslims.

In vitro characterization of cells derived from a patient with the GLA variant c.376A>G (p.S126G) highlights a non-pathogenic role in Fabry disease.

Fabry disease (FD) is a life-limiting disorder characterized by intracellular globotriaosylceramide (Gb3) accumulations. The underlying α-galactosidase A (α-GAL A) deficiency is caused by variants in the gene GLA. Variants of unknown significance (VUS) are frequently found in GLA and challenge clinical management. Here, we investigated a 49-year old man with cryptogenic lacunar cerebral stroke and the chance finding of the VUS S126G, who was sent to our center for diagnosis and initiation of a costly and life-long FD-specific treatment. We combined clinical examination with in vitro investigations of dermal fibroblasts (HDF), induced pluripotent stem cells (iPSC), and iPSC-derived sensory neurons. We analyzed α-GAL A activity in iPSC, Gb3 accumulation in all three cell types, and action potential firing in sensory neurons. Neurological examination and small nerve fiber assessment was normal except for reduced distal skin innervation. S126G iPSC showed normal α-GAL A activity compared to controls and no Gb3 deposits were found in all three cell types. Baseline electrophysiological characteristics of S126G neurons showed no difference compared to healthy controls as investigated by patch-clamp recordings. We pioneer multi-level cellular characterization of the VUS S126G using three cell types derived from a patient and provide further evidence for the benign nature of S126G in GLA, which is of great importance in the management of such cases in clinical practice.

Distribution of infectious and parasitic agents among three sentinel bee species across European agricultural landscapes.

Infectious and parasitic agents (IPAs) and their associated diseases are major environmental stressors that jeopardize bee health, both alone and in interaction with other stressors. Their impact on pollinator communities can be assessed by studying multiple sentinel bee species. Here, we analysed the field exposure of three sentinel managed bee species (Apis mellifera, Bombus terrestris and Osmia bicornis) to 11 IPAs (six RNA viruses, two bacteria, three microsporidia). The sentinel bees were deployed at 128 sites in eight European countries adjacent to either oilseed rape fields or apple orchards during crop bloom. Adult bees of each species were sampled before their placement and after crop bloom. The IPAs were detected and quantified using a harmonised, high-throughput and semi-automatized qPCR workflow. We describe differences among bee species in IPA profiles (richness, diversity, detection frequencies, loads and their change upon field exposure, and exposure risk), with no clear patterns related to the country or focal crop. Our results suggest that the most frequent IPAs in adult bees are more appropriate for assessing the bees' IPA exposure risk. We also report positive correlations of IPA loads supporting the potential IPA transmission among sentinels, suggesting careful consideration should be taken when introducing managed pollinators in ecologically sensitive environments.

An empirical investigation of definitions of subthreshold posttraumatic stress disorder.

Subthreshold posttraumatic stress disorder (PTSD) has long been recognized as an important construct that identifies a subgroup of individuals who report significant PTSD symptoms and associated disability but do not endorse enough symptoms to meet the criteria for a full PTSD diagnosis. Different investigators have defined subthreshold PTSD in various ways, making it difficult to interpret findings across studies. To address this problem, we systematically compared individuals who met criteria for nine different subthreshold PTSD definitions with individuals diagnosed with either full PTSD or no PTSD (i.e., failed to meet the criteria for a subthreshold definition) with respect to prevalence and associated clinical outcomes of interest. Participants were 1,082 veterans enrolled in the Veterans After Discharge Longitudinal Registry. PTSD and subthreshold PTSD diagnostic status were determined using the Structured Clinical Interview for DSM-5 (SCID-5) and validated self-report instruments were used to assess clinical outcomes. Across outcomes, subthreshold definitions generally identified a group of participants that was distinguishable from participants in both the PTSD and no PTSD groups, rs = .02-.47. We discuss the benefits and drawbacks of various subthreshold definitions and highlight the need for additional work evaluating these definitions across additional outcomes and samples. In the interim, we propose a working case definition of subthreshold PTSD as meeting any three of the four DSM-5 symptom criteria (i.e., Criteria B, C, D, and E) along with Criterion A and Criteria F-H. The results suggest subthreshold PTSD is a clinically meaningful construct.

Pesticide use negatively affects bumble bees across European landscapes.

Sustainable agriculture requires balancing crop yields with the effects of pesticides on non-target organisms, such as bees and other crop pollinators. Field studies demonstrated that agricultural use of neonicotinoid insecticides can negatively affect wild bee species1,2, leading to restrictions on these compounds3. However, besides neonicotinoids, field-based evidence of the effects of landscape pesticide exposure on wild bees is lacking. Bees encounter many pesticides in agricultural landscapes4-9 and the effects of this landscape exposure on colony growth and development of any bee species remains unknown. Here we show that the many pesticides found in bumble bee-collected pollen are associated with reduced colony performance during crop bloom, especially in simplified landscapes with intensive agricultural practices. Our results from 316 Bombus terrestris colonies at 106 agricultural sites across eight European countries confirm that the regulatory system fails to sufficiently prevent pesticide-related impacts on non-target organisms, even for a eusocial pollinator species in which colony size may buffer against such impacts10,11. These findings support the need for postapproval monitoring of both pesticide exposure and effects to confirm that the regulatory process is sufficiently protective in limiting the collateral environmental damage of agricultural pesticide use.

Within-patient association between emotion regulation and outcome in prolonged exposure for posttraumatic stress disorder.

OBJECTIVE: Difficulties with emotion regulation (ER) are a risk factor for the development and maintenance of posttraumatic stress disorder (PTSD). Less is known about temporal relations between ER and PTSD symptom change during treatment, including whether ER may represent a more potent change ingredient for some patients relative to others. This study examined the association between within-patient changes in ER and next-session PTSD symptom change and whether this association was more pronounced for patients with poorer baseline ER, more severe depression, or higher borderline personality disorder symptoms. METHOD: Data derived from a randomized controlled trial (NCT01600456) in which 149 adults with PTSD received up to 10 sessions of prolonged exposure (PE) or PE + sertraline. Patients rated difficulties with ER and PTSD symptoms repeatedly during treatment. Moderators were assessed at baseline. RESULTS: Cross-lagged, dynamic structural equation models revealed that ER improvements were associated with next-session reductions in PTSD (standardized effect = 0.13). PTSD symptom reduction was also associated with next-session ER improvement (standardized effect = 0.34). Moderator analyses revealed that the within-person ER-PTSD symptoms association was stronger for patients with higher baseline depression (standardized effect = 0.39). CONCLUSIONS: Reductions in PTSD symptoms may facilitate ER improvements during PE and PE augmented with sertraline rather than improvements in ER producing changes in PTSD symptoms. For patients with higher severity co-occurring depression, ER may represent a more active change ingredient. PE therapists could therefore consider placing particular emphasis on improving ER capabilities when working with this subgroup of patients. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Endothelial Cell Dysfunction and Hypoxia as Potential Mediators of Pain in Fabry Disease: A Human-Murine Translational Approach.

Fabry disease (FD) is caused by α-galactosidase A (AGAL) enzyme deficiency, leading to globotriaosylceramide accumulation (Gb3) in several cell types. Pain is one of the pathophysiologically incompletely understood symptoms in FD patients. Previous data suggest an involvement of hypoxia and mitochondriopathy in FD pain development at dorsal root ganglion (DRG) level. Using immunofluorescence and quantitative real-time polymerase chain reaction (qRT PCR), we investigated patient-derived endothelial cells (EC) and DRG tissue of the GLA knockout (KO) mouse model of FD. We address the question of whether hypoxia and mitochondriopathy contribute to FD pain pathophysiology. In EC of FD patients (P1 with pain and, P2 without pain), we found dysregulated protein expression of hypoxia-inducible factors (HIF) 1a and HIF2 compared to the control EC (p < 0.01). The protein expression of the HIF downstream target vascular endothelial growth factor A (VEGFA, p < 0.01) was reduced and tube formation was hampered in the P1 EC compared to the healthy EC (p < 0.05). Tube formation ability was rescued by applying transforming growth factor beta (TGFß) inhibitor SB-431542. Additionally, we found dysregulated mitochondrial fusion/fission characteristics in the P1 and P2 EC (p < 0.01) and depolarized mitochondrial membrane potential in P2 compared to control EC (p < 0.05). Complementary to human data, we found upregulated hypoxia-associated genes in the DRG of old GLA KO mice compared to WT DRG (p < 0.01). At protein level, nuclear HIF1a was higher in the DRG neurons of old GLA KO mice compared to WT mice (p < 0.01). Further, the HIF1a downstream target CA9 was upregulated in the DRG of old GLA KO mice compared to WT DRG (p < 0.01). Similar to human EC, we found a reduction in the vascular characteristics in GLA KO DRG compared to WT (p < 0.05). We demonstrate increased hypoxia, impaired vascular properties, and mitochondrial dysfunction in human FD EC and complementarily at the GLA KO mouse DRG level. Our data support the hypothesis that hypoxia and mitochondriopathy in FD EC and GLA KO DRG may contribute to FD pain development.

Characterisation of TbSmee1 suggests endocytosis allows surface-bound cargo to enter the trypanosome flagellar pocket.

All endocytosis and exocytosis in the African trypanosome Trypanosoma brucei occurs at a single subdomain of the plasma membrane. This subdomain, the flagellar pocket, is a small vase-shaped invagination containing the root of the single flagellum of the cell. Several cytoskeleton-associated multiprotein complexes are coiled around the neck of the flagellar pocket on its cytoplasmic face. One of these, the hook complex, was proposed to affect macromolecule entry into the flagellar pocket lumen. In previous work, knockdown of T. brucei (Tb)MORN1, a hook complex component, resulted in larger cargo being unable to enter the flagellar pocket. In this study, the hook complex component TbSmee1 was characterised in bloodstream form T. brucei and found to be essential for cell viability. TbSmee1 knockdown resulted in flagellar pocket enlargement and impaired access to the flagellar pocket membrane by surface-bound cargo, similar to depletion of TbMORN1. Unexpectedly, inhibition of endocytosis by knockdown of clathrin phenocopied TbSmee1 knockdown, suggesting that endocytic activity itself is a prerequisite for the entry of surface-bound cargo into the flagellar pocket.

Fertilizer and herbicide alter nectar and pollen quality with consequences for pollinator floral choices.

Background: Pollinating insects provide economically and ecologically valuable services, but are threatened by a variety of anthropogenic changes. The availability and quality of floral resources may be affected by anthropogenic land use. For example, flower-visiting insects in agroecosystems rely on weeds on field edges for foraging resources, but these weeds are often exposed to agrochemicals that may compromise the quality of their floral resources. Methods: We conducted complementary field and greenhouse experiments to evaluate the: (1) effect of low concentrations of agrochemical exposure on nectar and pollen quality and (2) relationship between floral resource quality and insect visitation. We applied the same agrochemcial treatments (low concentrations of fertilizer, low concentrations of herbicide, a combination of both, and a control of just water) to seven plant species in the field and greenhouse. We collected data on floral visitation by insects in the field experiment for two field seasons and collected pollen and nectar from focal plants in the greenhouse to avoid interfering with insect visitation in the field. Results: We found pollen amino acid concentrations were lower in plants exposed to low concentrations of herbicide, and pollen fatty acid concentrations were lower in plants exposed to low concentrations of fertilizer, while nectar amino acids were higher in plants exposed to low concentrations of either fertilizer or herbicide. Exposure to low fertilizer concentrations also increased the quantity of pollen and nectar produced per flower. The responses of plants exposed to the experimental treatments in the greenhouse helped explain insect visitation in the field study. The insect visitation rate correlated with nectar amino acids, pollen amino acids, and pollen fatty acids. An interaction between pollen protein and floral display suggested pollen amino acid concentrations drove insect preference among plant species when floral display sizes were large. We show that floral resource quality is sensitive to agrochemical exposure and that flower-visiting insects are sensitive to variation in floral resource quality.

Neural Circuits for Emotion.

Emotions are fundamental to our experience and behavior, affecting and motivating all aspects of our lives. Scientists of various disciplines have been fascinated by emotions for centuries, yet even today vigorous debates abound about how to define emotions and how to best study their neural underpinnings. Defining emotions from an evolutionary perspective and acknowledging their important functional roles in supporting survival allows the study of emotion states in diverse species. This approach enables taking advantage of modern tools in behavioral, systems, and circuit neurosciences, allowing the precise dissection of neural mechanisms and behavior underlying emotion processes in model organisms. Here we review findings about the neural circuit mechanisms underlying emotion processing across species and try to identify points of convergence as well as important next steps in the pursuit of understanding how emotions emerge from neural activity.

Carbon-biodiversity relationships in a highly diverse subtropical forest.

Carbon-focused climate mitigation strategies are becoming increasingly important in forests. However, with ongoing biodiversity declines we require better knowledge of how much such strategies account for biodiversity. We particularly lack information across multiple trophic levels and on established forests, where the interplay between carbon stocks, stand age, and tree diversity might influence carbon-biodiversity relationships. Using a large dataset (>4600 heterotrophic species of 23 taxonomic groups) from secondary, subtropical forests, we tested how multitrophic diversity and diversity within trophic groups relate to aboveground, belowground, and total carbon stocks at different levels of tree species richness and stand age. Our study revealed that aboveground carbon, the key component of climate-based management, was largely unrelated to multitrophic diversity. By contrast, total carbon stocks-that is, including belowground carbon-emerged as a significant predictor of multitrophic diversity. Relationships were nonlinear and strongest for lower trophic levels, but nonsignificant for higher trophic level diversity. Tree species richness and stand age moderated these relationships, suggesting long-term regeneration of forests may be particularly effective in reconciling carbon and biodiversity targets. Our findings highlight that biodiversity benefits of climate-oriented management need to be evaluated carefully, and only maximizing aboveground carbon may fail to account for biodiversity conservation requirements.

Comparing the Prevalence of Probable DSM-IV and DSM-5 Posttraumatic Stress Disorder in a Sample of U.S. Military Veterans Using the PTSD Checklist.

Posttraumatic stress disorder (PTSD) changed substantially when Diagnostic and Statistical Manual of Mental Disorders transitioned from fourth (DSM-IV) to fifth (DSM-5) edition. Hoge et al. found that although diagnostic prevalence remained consistent across nomenclatures, diagnostic concordance was low (55%). Study goals were to examine both the generalizability of these findings and whether either diagnosis systematically excluded patients. U.S. veterans (N = 1,171) who completed the PTSD Checklist for DSM-IV (PCL-S) and DSM-5 (PCL-5) were classified as: probable PTSD on both measures; probable PTSD on PCL-S only; probable PTSD on PCL-5 only; or no PTSD on either measure. Diagnostic prevalence was equivalent. Unlike Hoge et al.'s findings, diagnostic concordance was high (91.3%). Furthermore, observed demographic and severity differences were driven by disparities between veterans in the no PTSD versus the probable PTSD groups, not diagnostic changes. Findings suggest translatability across measures and that diagnostic changes do not systematically exclude patients.

The Effect of Night Float Rotation on Resident Sleep, Activity, and Well-Being.

BACKGROUND: Night float call systems are becoming increasingly common at training programs with the goal of reducing fatigue related to sleep deprivation and sleep disturbance. Previous studies have shown that trainees obtain less sleep during the night float rotation and have decreased sleep efficiency for several days after the rotation. The impact on physical and emotional well-being has not been documented. METHODS: Twenty-seven anesthesia residents were enrolled in a study using wearable sleep and activity trackers and National Institutes of Health Patient-Reported Outcome Measurement Information System (NIH PROMIS) surveys for sleep disturbance, fatigue, and positive affect to record data the week before ("baseline"), during ("night float"), and 1 week after ("recovery") their night float rotation. Each subject's data during the night float week and recovery week were compared to his or her own baseline week data using a paired, nonparametric analysis. The primary outcome variable was the change in average daily sleep hours during the night float week compared to the baseline week. Average daily rapid eye movement (REM) sleep, daily steps, and NIH PROMIS scores comparing night float and recovery weeks to baseline week were prespecified secondary outcomes. NIH PROMIS scores range from 0 to 100 with 50 as the national mean and more of the construct having a higher score. RESULTS: There was no difference in average daily sleep hours between the night float and the baseline weeks (6.7 [5.9-7.8] vs 6.7 [5.5-7.7] hours, median [interquartile range]; P = .20). Residents had less REM sleep during the night float compared to the baseline weeks (1.1 [0.7-1.5] vs 1.4 [1.1-1.9] hours, P = .002). NIH PROMIS fatigue scores were higher during the night float than the baseline week (58.8 [54.6-65.1] vs 48.6 [46.0-55.1], P = .0004) and did not return to baseline during the recovery week (51.0 [48.6-58.8], P = .029 compared to baseline). Sleep disturbance was not different among the weeks. Positive affect was reduced after night float compared to baseline (39.6 [35.0-43.5] vs 44.8 [40.1-49.6], P = .0009), but returned to baseline during the recovery week (43.6 [39.6-48.2], P = .38). CONCLUSIONS: The residents slept the same number of total hours during their night float week but had less REM sleep, were more fatigued, and had less positive affect. All of these resolved to baseline except fatigue, that was still greater than the baseline week. This methodology appears to robustly capture psychophysiological data that might be useful for quality initiatives.

WhatsApp supervision for a lay-led Islamic trauma-focused intervention in Somaliland: Qualitative content analysis.

Clinical supervision is critical for the uptake of psychotherapy but difficult to facilitate in countries with limited providers, resources, and internet infrastructure. Innovative supervision approaches are needed to increase access to mental health treatments in low-to-middle income countries (LMICs). This study examined the content and feasibility of remote WhatsApp text supervision conducted as part of an open clinical trial in Somaliland. Islamic Trauma Healing ITH) is a brief, group, lay-lead, trauma-focused, mosque-based intervention that has demonstrated initial efficacy in pilot studies in the United States and Somaliland. After a 2-day, in-person training, lay leaders led four groups of five to seven members focused on trauma-related psychopathology and community reconciliation. Somali lay leaders trained in ITH (n = 9) and the research team (n = 6) attended weekly WhatsApp supervision during the intervention. Content was logged and subjected to qualitative analysis by two coders. Comments related to intervention implementation indicated that lay leaders understood the treatment rationale, adhered to treatment procedures, and believed the intervention components to be helpful and culturally relevant. Themes related to engagement suggested perfect attendance across groups and high levels of participation. Lay leader psychoeducation and skill development; supervisor praise, support, and encouragement; and supervisee gratitude emerged as additional themes. Remote text supervision conducted via WhatsApp was technologically feasible and may have facilitated skill development and the effective implementation of this lay-led intervention. When tailored to the local context, remote supervision approaches hold promise for increasing access to services in LMICs with limited resources.

Nutritional stress exacerbates impact of a novel insecticide on solitary bees' behaviour, reproduction and survival.

Pesticide exposure and food stress are major threats to bees, but their potential synergistic impacts under field-realistic conditions remain poorly understood and are not considered in current pesticide risk assessments. We conducted a semi-field experiment to examine the single and interactive effects of the novel insecticide flupyradifurone (FPF) and nutritional stress on fitness proxies in the solitary bee Osmia bicornis. Individually marked bees were released into flight cages with monocultures of buckwheat, wild mustard or purple tansy, which were assigned to an insecticide treatment (FPF or control) in a crossed design. Nutritional stress, which was high in bees foraging on buckwheat, intermediate on wild mustard and low on purple tansy, modulated the impact of insecticide exposure. Within the first day after application of FPF, mortality of bees feeding on buckwheat was 29 times higher compared with control treatments, while mortality of FPF exposed and control bees was similar in the other two plant species. Moreover, we found negative synergistic impacts of FPF and nutritional stress on offspring production, flight activity, flight duration and flower visitation frequency. These results reveal that environmental policies and risk assessment schemes that ignore interactions among anthropogenic stressors will fail to adequately protect bees and the pollination services they provide.