Outlier patients - those residing in a ward outside that of the specialty caring for them - often experience delays due to lack of specialty-specific equipment. This study evaluated whether introducing a portable Orthopaedic 'Grab Bag' containing essential equipment improved the efficiency of reviewing and treating Orthopaedic outlier patients in a major trauma centre (MTC) and a trauma unit (TU). A prospective study was conducted at both a London MTC and a TU. Equipment retrieval times for common Orthopaedic procedures (including removal of plaster backslabs, removal of staples from a wound, joint aspiration, wound suturing, application of a polysling, skin traction) were measured under two conditions: standard collection versus use of a prepacked Orthopaedic Grab Bag. The primary outcome was total equipment retrieval time. At the MTC, modal retrieval time decreased from 5-10 minutes to 0-5 minutes post-implementation, with no retrievals exceeding 10 minutes (previously up to 30 minutes). The proportion completed within 5 minutes rose from 21.7% to 64.3%. At the TU, pre-intervention 50% of retrievals were completed within 5 minutes and 15.3% exceeded 10 minutes; post-intervention, all were completed within 5 minutes. The greatest improvements were seen in removal of plaster backslabs (437 seconds faster), polysling application (432 seconds faster) and staple removal from wounds (358 seconds faster). Implementation of an Orthopaedic Grab Bag improved equipment retrieval efficiency significantly in both MTC and TU settings. This low-cost, scalable intervention enhances the timeliness of Orthopaedic outlier care.
Adults with low socioeconomic status (SES) experience profound tobacco-related health disparities. This paper describes the development of a mobile application, iQuit Mindfully 2.0, to provide accessible mindfulness training for smoking cessation for adults with low SES. In the initial usability study, adults with low SES who smoked (N = 16) used the app for 2 weeks and provided feedback through individual interviews, which were coded using NVivo. Participants appreciated that the app was simple and easy to use, relatable and personalized, and taught mindfulness practices for coping with stress and cravings. The app helped them reduce their smoking, develop greater confidence in their ability to cope with cravings, and recover from smoking lapses. Participants suggested ways to increase interactivity and social support, improve smoking behavior tracking, and enhance app esthetics. This feedback will be used to improve the app with the goal of providing accessible smoking cessation treatment for low-SES populations.
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The neurotransmitter acetylcholine (ACh) is essential in both the central and peripheral nervous systems. Recent studies highlight the significance of interactions between ACh and various neuromodulators in regulating complex behaviors. The ability to simultaneously image ACh and other neuromodulators can provide valuable information regarding the mechanisms underlying these behaviors. Here we developed a series of red fluorescent G-protein-coupled receptor activation-based ACh sensors, with a wide detection range and expanded spectral profile. The high-affinity sensor rACh1h reliably detects ACh release in various brain regions, including the nucleus accumbens, amygdala, hippocampus and cortex. Moreover, rACh1h can be coexpressed with green fluorescent sensors to record ACh release together with other neurochemicals in various behavioral contexts using fiber photometry, mesoscopic imaging and two-photon imaging with high spatiotemporal resolution.
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Wastewater-based surveillance (WBS) has emerged as a valuable tool for population-level monitoring of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission, yet the interplay between sampling strategies and disease prevalence in shaping detection performance remains ambiguous. We investigated how grab and composite sampling influence SARS-CoV-2 ribonucleic acid (RNA) detection dynamics and predictive lag times across high- and low-prevalence communities in Selangor, Malaysia. A 28-week longitudinal study was conducted in Selangor, Malaysia, comparing grab and composite wastewater sampling in communities with high and low Coronavirus disease 2019 (COVID-19) prevalence. SARS-CoV-2 RNA in 348 samples was quantified using digital Reverse Transcription Polymerase Chain Reaction (RT-dPCR), and viral lineages were characterized by Nanopore sequencing. Detection sensitivity and lead times relative to reported cases were evaluated. In low-prevalence settings, grab sampling showed higher detection sensitivity than composite sampling (92.0% vs. 70.0%), whereas both methods achieved similarly high detection in high-prevalence areas (>97.0%). Lag-time analysis indicated that grab sampling in high-prevalence settings was significantly associated with case trends at potential two-week lead (p = 0.024), while composite sampling in low-prevalence settings showed the strongest association at a potential one-week lead (p = 0.0022). Overall, lag structures varied by both sampling strategy and prevalence context. Both sampling approaches captured the replacement of Omicron sublineages (XBB.1.5, XBB.1.9.1, XBB.1.16) and identified additional circulating variants, including EG.5, that were not captured in the available clinical sequencing dataset during the same period. These findings reveal that local transmission intensity is associated with the utility of different sampling designs. Context-specific optimization of WBS sampling strategies enhances sensitivity, reduces detection lag, and strengthens early warning and genomic-tracking capacity in public health surveillance frameworks.
Tyre-related chemicals are emerging environmental pollutants. They can reach the aquatic environment via sustainable drainage systems (e.g., retention ponds). However, little is known about tyre chemicals in these engineered environments which themselves are important ecosystems. A key challenge of monitoring tyre chemicals is their changeable concentrations caused by road runoff. Therefore, it was proposed to establish a longer-term monitoring approach (e.g., ≥ 7 days) to complement low frequency grab sampling for improved fate and exposure assessments. A hydrophilic-lipophilic balance-Chemcatcher passive sampler configuration was assessed for uptake of 11 tyre-related chemicals including 1,3-diphenylguanidine, hexamethoxymethylmelamine (HMMM), and N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-quinone). Ex-situ 14-day uptake calibrations showed linear uptake (r2 values ≥ 0.9) in pond water with sampling uptake rates (RS) in the range 0.0073 - 0.054 L/d. Both water temperature and flow velocity had a significant effect (p-value < 0.05) on RS value for some chemicals. Subsequent in-situ monitoring revealed little reduction in tyre chemical concentrations through two retention pond systems. Nevertheless, 7-day and 14-day time weighted average concentrations were below the provisional predicted no effect concentration (PNEC) for most chemicals. However, all samples exceeded the current PNEC for HMMM (1.7 × 10-2 µg/L) and by ≥ 20 times for some samples suggesting need for 'upstream' or within pond intervention. Non-targeted analysis tentatively identified a further 20 potential chemicals of interest in Chemcatcher extracts including vulcanisation accelerators, plasticisers and transformation products. Overall, the proposed Chemcatcher passive sampler can complement grab sampling to better monitor tyre-related chemicals in surface waters for their improved management.
Wastewater surveillance can be used to monitor Salmonella enterica serovar Typhi (S Typhi) transmission in the community, allowing early outbreak detection and vaccine effect evaluation. This study aims to establish the baseline detection rate of S Typhi in wastewater and to evaluate its relationship with the clinical burden of typhoid before typhoid conjugate vaccine (TCV) introduction in an endemic urban context. We conducted wastewater surveillance for S Typhi in Vellore, Tamil Nadu, India, from Dec 12, 2022, to June 30, 2023, before implementing a cluster-randomised trial of a TCV. 723 grab and 723 Moore swabs were collected from 50 sampling locations and concentrated using Nanotrap A beads for grab samples and Moore swabs as a passive sampler. S Typhi was detected using multiplex quantitative PCR targeting ttr, staG, and tviB genes. Blood culture-confirmed cases of typhoid fever were recorded through hospital-based surveillance established as a part of an independent ongoing VeVact study, an observer-blinded, cluster-randomised trial of a TCV (TyphiBEV). We calculated proportions of typhoid positivity in wastewater sampling sites and the incidence rates of blood culture-confirmed typhoid cases. Spatial analysis was performed to detect statistically significant hotspots for typhoid fever cases in the study area. Bayesian inference using the integrated nested Laplace approximation and mixed-effects spatiotemporal regression quantified associations between wastewater S Typhi detection and typhoid incidence. S Typhi was detected in 80 (5·5%) of 1446 wastewater samples, higher in grab samples (60 [8·3%] of 723) than in Moore swabs (20 [2·8%] of 723). 207 typhoid cases were recorded, with cases peaking between March and May, 2023. Spatial clustering of typhoid cases corresponded with higher wastewater S Typhi detection. The proportion of wastewater samples that were positive over the study period correlated with typhoid incidence when analysed across the 60 vaccine trial clusters (Spearman's ρ=0·32; p=0·014) or the non-overlapping wastewater site catchment areas (ρ=0·57; p<0·0001). Mixed-effects logistic regression adjusting for spatiotemporal random effects, levels of human faecal contamination, rainfall, and laboratory processing method, gave a 2·43 (95% CI 1·38-4·27) times higher odds of detecting S Typhi in wastewater samples for each 10-fold increase in typhoid fever incidence. Wastewater surveillance data correlate with clinical disease incidence in an endemic setting and could be used to monitor targeted interventions, including TCV introduction. The Gates Foundation.
To date, research on gestural communication in species other than great apes has been quite limited, especially in their natural habitat, although including a broader range of species in different settings is essential for identifying evolutionary patterns and determining whether some of the fundamental characteristics of human communication are widely shared across primates. In this study, we specifically aimed to explore the use of gestural sequences in Geoffroy's spider monkeys (Ateles geoffroyi), a species for which research on gestural communication remains scarce. To this end, we conducted behavioral observations, recording focal video samples of a wild group of 54 individuals. From the videos, we coded all gestures (N = 709), of which 182 occurred alone and 527 occurred within 125 sequences, which mostly consisted of 2-4 successive gestures. The odds of producing gestural sequences rather than single gestures were higher in the contexts of play, aggression and sexual behavior. In contrast, there was no significant effect of signaler's sex and age on the odds of producing a gestural sequence rather than a single gesture. Only three sequences (i.e., embrace-pectoral sniff, push-present climb, grab-grab pull) occurred more than twice and were not mere repetitions of the same gesture type. Our results show that gestural sequences are used by platyrrhines in several different contexts, although more studies are needed to understand their function. Hasta la fecha, la investigación sobre comunicación gestual en especies distintas a los grandes simios ha sido limitada, especialmente en su hábitat natural, aunque incluir un abanico más amplio de especies en diferentes contextos es esencial para identificar patrones evolutivos y determinar si las caracteristicas fundamentales de la comunicación humana son exclusivas de los grandes simios o están más ampliamente compartidas entre los primates. En este estudio, exploramos el uso de secuencias gestuales en el mono araña de Geoffroy (Ateles geoffroyi), una especie para la cual la investigación sobre comunicación gestual sigue siendo escasa. Con este fin, realizamos observaciones de comportamiento, registrando muestras focales de un grupo silvestre compuesto por 54 individuos. A partir de los vídeos, codificamos todos los gestos (N = 709), de los cuales 182 ocurrieron como gestos únicos y 527 dentro de 125 secuencias, que en su mayoría incluían entre 2 y 4 gestos. Las odds de producir una secuencia gestual en lugar de un gesto único fue máyor en contextos de juego, agresión o sexuales. En contraste, no se encontró ningún efecto significativo del sexo y de la edad del emisor sobre las odds de producir una secuencia gestual en lugar de un gesto único. Solo tres secuencias (es decir, abrazo‐olfateo pectoral, empujón‐presentación para trepar y agarre‐tirón) ocurrieron más de dos veces y no fueron meras repeticiones del mismo tipo de gesto. Nuestros resultados muestran que las secuencias gestuales también son utilizadas por platirrinos en diferentes contextos, aunque se necesitan más estudios para comprender su función.
Cadmium (Cd) contamination poses a serious threat to aquatic ecosystems and human health. Duckweed has been recognized as a promising plant for phytoremediation of heavy metal-polluted water, yet the signaling mechanisms underlying its response to Cd stress remain poorly understood. Dopamine (DA), a catecholamine known as a neurotransmitter in animals, has recently been identified as a potential regulatory molecule in plants, but its dynamic response under heavy metal stress has not been clearly characterized. In this study, dopamine signaling dynamics in duckweed (Lemna turionifera 5511) were investigated using the genetically encoded fluorescent dopamine sensor GRAB-DA2h. Stable transgenic duckweed lines expressing the sensor were generated via Agrobacterium-mediated transformation, enabling real-time visualization of intracellular dopamine changes. With Cd treatment, GRAB-DA2h fluorescence in root tissues increased within 1 minute and remained elevated during the imaging period, indicating a rapid early signaling response. Following a 24-hour exposure to 50 mM CdCl2, the protoplasts isolated from fronds exhibited an increase in fluorescence intensity from 345.18 to 391.14, while those derived from roots showed an increase from 112.75 to 140.68. These findings provide direct evidence of dopamine signaling dynamics in duckweed under cadmium stress and demonstrate the applicability of genetically encoded biosensors for studying plant stress signaling. This work offers new insights into plant responses to heavy metal stress and may contribute to improving phytoremediation strategies.
Managing salinity in arid rivers is impeded by sparse monitoring, relying on low-frequency grab samples that miss hydrological event dynamics. Here, interpretable machine learning is applied to a 50-year monthly archive (1968-2018; Discharge, major ions, pH) from three stations on Iran's Karkheh River. Gradient Boosting Regression achieves high predictive skill for Total Dissolved Solids (TDS)/Electrical Conductivity (EC) (test-set R2 = 0.94/0.97; RMSE = 55 mg L-1/56 µS cm-1), validated via time-aware cross-validation. SHAP-based feature attribution reveals that Na+ and SO4-2 are the strongest contributors to TDS, while Na+ and Cl- dominate EC, consistent with conservative salinity sources under baseflow conditions. A reduced-input decision tree (four predictors) retains R2 = 0.81-0.87, enabling minimal-sensor monitoring. Flow-regime partitioning and STL (Seasonal-Trend decomposition using Locally estimated scatterplot smoothing)-detrended event composites reveal low-flow salinization and ion-specific post-flood recovery (Cl-: 1-2 months; Na+: 2-3 months), guiding targeted sampling. This framework extracts predictive power, process associations, and operational guidance from legacy grab-sample archives, scalable to data-limited basins worldwide.
Synthetic musks (SMs) are rarely included in routine monitoring programs and are typically investigated only in wastewater-impacted environments. There is limited understanding of their potential sources and transport from industrial and other urban areas. This study investigates the occurrence of SMs in urban waterways across the greater Melbourne area, Australia, by examining land-use associations. Sampling methods were also assessed by comparing grab water sample collection against trimethylpentane (TRIMPS) and Chemcatcher SDB-XC passive samplers. Surface water samples from 20 sites were extracted and analysed via solid-phase extraction and gas chromatography-mass spectrometry. Passive samplers detected a higher number of SMs (eight) compared to grab samples (four). Eight SMs-galaxolide, tonalide, cashmeran, celestolide, traseolide, phantolide, and musk ambrette and musk ketone-were detected in urban waterways, with SMs present at 70% of sites. No statistically significant land-use associations were found for SMs, yet distinct patterns emerged. Galaxolide reached the highest concentrations (up to 1550 ng/L) and detection frequency in wastewater- and residential-impacted areas. Tonalide and galaxolide were detected in rural sites implying widespread use and possibly atmospheric transport. Cashmeran had a higher incidence of detection at residential sites, while musk ketone-internationally regulated in cosmetics-was highest in industrial areas, suggesting possible non-cosmetic sources. Polycyclic musks and nitro musks were present throughout the urban environment highlighting the need for continued monitoring and further research on their environmental distribution and impact.
Respiratory protective textiles increasingly require multifunctional surface treatments that enhance durability and provide active antiviral performance without compromising filtration. In this context, this study develops graphene nanoplatelet-silver nanoparticle (GNP-Ag) and super activated carbon-silver nanoparticle (SAC-Ag) composite coatings for PPE-grade nonwoven fabrics using a room-temperature ultrasonic atomization process. The coatings enhanced mechanical integrity while maintaining baseline filtration efficiency. GNP-Ag increased spunbond grab strength by 54% and, when combined with polyurethane and UV cross-linking, improved meltblown strength by 47%. Surface wettability shifted from hydrophilic to hydrophobic, with meltblown contact angle increasing from 88° to 121°, and wash fastness improved following heat and UV curing. Cytotoxicity assays showed a dose-dependent response, with GNP-Ag exhibiting lower cytotoxicity compared with SAC-Ag. Antiviral testing against human coronavirus OC43 demonstrated a 1.93-log reduction (98.8%) after 10 min for unwashed GNP-Ag fabrics and a 1.43-log reduction (96.3%) after washing. Filtration performance remained unchanged for GNP-Ag and slightly increased for SAC-Ag. These results demonstrate a stable, mechanically reinforcing, and antiviral coating that enhances the protective function of PPE-grade nonwoven fabrics.
This experiment evaluated intake, nutrient digestibility, growth rates, and metabolic responses of Bos indicus beef heifers fed Bacillus spp. when offered a low-quality tropical hay [≤5% crude protein (CP)] and then transitioned to lush pastures during the early vegetative stage. Nellore heifers (n = 48; 20 ± 1 mo) were ranked by initial body weight (BW; 312 ± 26.4 kg) and randomly assigned to Tifton 85 hay-based diet and a protein supplement offered at 0.30% BW with or without (CON; n = 24) the inclusion of a Bacillus-based direct-fed microbial (DFM; BAC; n = 24). Animals were housed individually throughout the experiment, resulting in 48 drylot pens. The experimental period lasted 140 d, while individual full BW and blood samples were collected every 28 d. In the last 3 d of each 28-d period, fecal grab samples were collected from all heifers to assess the apparent total-tract digestibility. After the dry season, heifers were transitioned into lush pastures for 15 d and offered the same treatments (total experimental period = 156 d). Dry matter (DM) availability was measured at the beginning and end of the grazing period, whereas BW and blood samples were collected over the 15-d period. All data were analyzed with SAS (version 9.4). During the dry season, no treatment effects were observed (P ≥ 0.20) for feed intake or ADG. Dry matter and CP digestibility were greater for BAC (P ≤ 0.05). Heifers fed BAC had greater blood urea-N (BUN) and plasma insulin-like growth factor-I (IGF-I; P ≤ 0.02), while mean serum glucose tended (P = 0.09) to be greater. Treatment × day effects (P < 0.01) were observed on BW change during the 15-d grazing season. The BAC-fed heifers tended to lose (P ≤ 0.09) more BW from day 0 to 1, but gained (P < 0.01) more BW from days 0 to 15 of the period. During the 15-d grazing period, heifers fed BAC had a greater overall BW change and average daily gain (ADG) when compared with CON cohorts (P < 0.01). No differences were observed for DM availability at the beginning of the grazing period (P = 0.61), whereas paddocks assigned to BAC heifers had less DM available after 15 d (P = 0.02). In summary, feeding Bacillus spp. increased DM and CP digestibility, serum hormones and metabolites associated with energy and protein metabolism in beef heifers fed a low-quality tropical hay, without effects on growth rates. When the heifers were transitioned to lush pastures for 15 d, Bacillus spp. supplementation improved the growth rate of the heifers, positively impacting the entire growth of the herd.
An aging population is a major demographic transition with significant implications for healthcare systems, particularly in low- and middle-income countries. Ensuring age-friendly healthcare services is essential to meet the complex needs of the elderly population. The objective of this study was to assess the elderly friendliness of government and private hospitals in Ernakulam district, Kerala, India. A cross-sectional study was conducted among 70 hospitals (34 government and 36 private) with inpatient facilities in Ernakulam district. A structured checklist was used to assess six domains: accessibility, medical care services, physical environment, inpatient services, admission and billing, and spiritual environment. Data were collected through interviews with administrative personnel and direct observation and analyzed using descriptive and inferential statistical methods. The mean elderly friendliness score was 27.36 ± 4.78. Overall, 31 (44.3%) hospitals were classified as elderly friendly. Among these, a higher proportion were private hospitals (52.8%) compared with government hospitals (35.3%). The physical environment domain showed the highest performance, whereas accessibility performed the poorest. Private hospitals scored significantly higher in admission and billing (p=0.002) and spiritual environment (p=0.001). Government hospitals showed higher scores in medical care services, but the difference was not statistically significant (p=0.057). No significant difference was observed in overall elderly-friendliness scores between the two sectors (p=0.369). Less than half of the hospitals in the study were elderly friendly, with major gaps in accessibility infrastructure, geriatric care services, and safety features such as grab rails in toilets. Strengthening hospital accessibility, improving geriatric training among healthcare personnel, and implementing standardized age-friendly policies are required to improve elderly healthcare services.
Freshwater ecosystems are increasingly exposed to complex mixtures of pesticides and pharmaceutical compounds, raising concerns about their accumulation in aquatic organisms and implications for biomonitoring. While bioaccumulation has been widely studied in fish and invertebrate soft tissues, the potential role of freshwater gastropod shells as accumulation sites remains largely unexplored. In this study, we explored the occurrence and bioaccumulation of 58 organic pollutants (13 antibiotics, 30 pesticides, and 15 pharmaceuticals) in shells and soft tissues of freshwater gastropods, and correlated these concentrations to contaminant concentrations in one grab water sample and one suspended sediments sample from the Orge River (France). Pollutant concentrations in gastropods were not related to concentrations in water but were significantly correlated with concentrations measured in suspended sediments, highlighting particle-associated exposure as a possible pathway. Overall, soft tissues exhibited higher concentrations and more consistent detection frequencies than shells, except for antibiotics, for which no significant difference was observed. Bioaccumulation factors in soft tissues were generally low, even if high values were observed for diflufenican, tebuconazole, and propranolol. Our results suggest that although gastropod shells can accumulate organic pollutants, soft tissues provide a more reliable and mechanistically interpretable matrix for biomonitoring. Combining biological measurements with suspended sediment analyses appears essential for realistic environmental risk assessment in freshwater systems. These findings should be explored in future studies including broader spatial and temporal replication.
We aimed to evaluate the long-term effects of systemic ceftiofur (CEF) and ampicillin (AMP) on the abundance and duration of fecal shedding of resistant Gram-negative (GN) bacteria from healthy dairy cows, as compared to cows that did not receive antibiotic treatment. Healthy lactating Holstein cows were randomly assigned to receive once daily treatments for 5 days with CEF (2.2 mg/kg subcutaneously, n = 8), AMP (11 mg/kg intramuscular, n = 8) or isotonic sodium chloride solution (25 cc, subcutaneously, n = 8). Fecal grab samples were collected before the initial treatment (day 0) and weekly for 11 weeks, beginning 2 days after the final treatment. Briefly, samples were diluted and inoculated in duplicate using a spiral plater on MacConkey agar or MacConkey agar supplemented with AMP or CEF. The phenotypic abundance of GN bacteria resistant to AMP or CEF was enumerated using a logarithmic scale and as a proportion of the total number of GN bacteria. Generalized linear mixed models for repeated measurements were used to compare the abundance of resistant bacteria among treatments over a 12-week clinical trial period. The abundance of GN bacteria did not vary within or among treatments over the weeks of the trial. The abundance of GN bacteria resistant to AMP and CEF did not differ among treatment groups within a given week. After treatment, systemic treatment with AMP or CEF did not increase the proportion of resistant GN bacteria in feces of treated cows as compared to a control group that did not receive antibiotic treatment. Our preliminary molecular results suggest that the overall bacterial composition remained similar across groups. The relative abundance of antimicrobial resistance genes (ARG) revealed that the macrolide-lincosamide-streptogramin B (MLS), aminoglycoside, tetracycline, and elfamycin classes were the most predominant, whereas beta-lactams were moderate, ranging from 4 to 7%. In summary, a long-term effect of systemic treatment with AMP or CEF in healthy dairy cows produced minimal changes in the abundance of resistant GN bacteria, which indicates that systemically administered treatments of AMP and CEF had similar effects on the abundance and duration of resistant bacteria shedding in feces.
Perfluorooctane sulfonate (PFOS), a member of the per- and polyfluoroalkyl substances family, is highly bioaccumulative and remains a persistent public health concern for consumers of wild freshwater fish. However, testing fish tissue for PFOS is time-consuming and costly, and it requires fish mortality. To reduce these costs by furthering the understanding of controls on PFOS bioaccumulation, we analyzed 3,831 paired fish tissue and surface water grab samples collected between 2006 and 2023 from 185 sites in Colorado, Minnesota, and Wisconsin, United States. We found that surface water samples reliably predict PFOS concentrations in fish filets. Species-averaged tissue PFOS scales log-linearly with water PFOS (R2 = 0.49). Adding fish taxonomy modestly improves fit (R2 = 0.69), while fish length, feeding guilds, and habitat preferences contribute little compared with water concentration. Decision tests tied to common fish consumption advisory targets (3.9-200 ng/g) yield surface water thresholds of ∼2.3-26.2 ng/L and strong classification abilities (AUC 0.85-0.97). We posit that surface water PFOS is a practical, defensible proxy for fish PFOS that can accelerate protection while improving efficiency. Regulatory agencies could adopt a tiered framework using surface water PFOS concentrations to triage waterbodies for fish sampling, thus reducing costs, limiting fish mortality, and enabling timely, consistent advisories.
Cortical control of movement is a distributed computation spanning multiple densely interconnected regions. Although we have rich anatomical atlases and a coarse understanding of how function maps to areas and subregions, we lack a detailed account of how behaviorally relevant activity is organized across the cortical sheet. Here, we trained head-fixed mice to perform a 15-target reach-to-grasp task while we performed cellular-resolution, two-photon calcium imaging across five regions of sensorimotor cortex (>39,000 layer 2/3 neurons). We characterized each neuron's trial-averaged peri-event activity with interpretable metrics and mapped these response properties across areas, revealing large-scale spatial structure. Neuronal response profiles often shifted abruptly at anatomical borders: motor areas showed sharper tuning and more linear relationships with target location, whereas somatosensory areas displayed more heterogeneous response patterns. Neural response properties also differed according to somatotopic representation. Nonlinear dimensionality reduction of the neural feature matrix revealed that areas varied in their average response profiles, but that areas did not have well-separated feature distributions; instead, each area contained subpopulations. Neurons in each subpopulation had characteristic response profiles and were distributed across multiple cortical areas. The spatial distributions of the subpopulations overlapped, with neurons from different subpopulations salt-and-pepper intermingled in the overlap zones. Together, these results describe novel activity structure across sensorimotor cortex and identify several distinct but spatially overlapping subpopulations with characteristic activity patterns during reach-to-grasp behavior. Reaching out to grab a cup of coffee may feel effortless, but it requires the brain to coordinate a precise sequence of movement commands. This control is supported by the sensorimotor cortex, the part of the brain's wrinkled outer layer involved in integrating incoming sensory feedback with outgoing movement commands. Researchers have traditionally divided the sensorimotor cortex into separate anatomical areas based on the shapes of neurons as well as their connectivity to other brain structures. This area-based view has shaped our understanding of the sensorimotor cortex based on the idea that different areas generally serve different functions. However, it has been less clear whether these functions change sharply at the borders dividing regions or whether groups of neurons within an area might perform different functions. Anatomical areas have long formed the basic unit for studying cortical function, yet recent work shows that movement-related activity is far more widely distributed than this view assumes. Understanding how the cortex controls movement, therefore, requires mapping the responses of large numbers of individual neurons across different areas, and determining how responses relate to known anatomical and somatotopic boundaries. Salimian, Grier and Kaufman sought to characterize how responses of single neurons are distributed across anatomically defined sensorimotor areas in the cortex of mice while they performed reach-to-grasp movements. Salimian et al. characterized the activity of nearly 40,000 individual neurons across different areas of the sensorimotor cortex of mice using interpretable features obtained from their activity during a challenging forelimb control task. Neural response features were then organized into coherent spatial gradients spanning motor and somatosensory cortical areas. The results showed that the spatial patterns possessed sharp transitions that closely aligned with anatomical and somatotopic borders. Clustering cells based on their features identified four unique subpopulations with characteristic response profiles, whose members were widely distributed across all recorded areas, but with different prevalence in each. The spatial distributions of these subpopulations formed overlapping zones, in which neurons from different subpopulations intermingled. The findings of Salimian et al. suggest that a complete understanding of the sensorimotor cortex requires mapping the distributed neuronal networks, instead of just focusing on separate, specialized areas. In the future, this view could inform clinical technologies such as the placement of recording electrodes for brain-computer interfaces that help paralyzed people move, or stimulation-based maps used to guide surgical resection of brain tissue. In addition, they may inform the design of neural networks for controlling robots, where sensory feedback must be integrated into choosing motor commands. However, realizing such benefits would first require confirming that these subpopulations exist in the human brain and elucidating their contributions to movement control.
The dorsolateral striatum (DLS) is a key site for coordinating the alcohol-induced stimulant response, a behavioral marker predictive of future alcohol use disorder. Although ethanol (EtOH) affects all brain cells, little is known about the contribution of non-neuronal DLS cell types to EtOH-induced stimulation. We used ex vivo two photon calcium imaging, in vivo fiber photometry of astrocyte and neuronal GCaMP, and astrocyte-specific manipulations in mice to determine DLS astrocyte contributions to EtOH-induced stimulation and voluntary EtOH drinking behavior. Using fiber photometry of GRAB-ACh sensors and cell-type specific chemogenetics, we also assessed the role of cholinergic signaling in observed astrocyte EtOH effects. As expected, intraperitoneal EtOH injections (0.5-2g/kg) evoked a stimulant response, evidenced by increased locomotion compared to saline. In parallel, EtOH dose-dependently decreased astrocyte calcium activity but had minimal effects on direct and indirect pathway neuronal activity. Mimicking this reduction with astrocyte-specific expression of CalEX, a calcium extruding pump, facilitated EtOH stimulation compared to mice expressing a control fluorophore. Hence, EtOH-induced suppression of DLS astrocyte activity contributes to stimulation. Astrocyte calcium signaling is a well-known target of neuromodulation. Fiber photometry recordings of extracellular acetylcholine (ACh) levels via GRAB-ACh imaging showed inhibition of ACh release by acute EtOH. We virally expressed the excitatory chemogenetic actuator hM3Dq in striatal cholinergic interneurons to assess whether artificially increasing ACh release blocks EtOH-induced inhibition of astrocytic calcium activity. Despite facilitating ACh release, this manipulation did not impact astrocyte calcium activity under control (saline) or EtOH conditions. Together, this work identifies DLS astrocytes as key contributors to EtOH-induced stimulation and highlights the importance of considering astrocyte-neuron interactions in evaluating alcohol effects.