Synergistic effect of phytic acid and eggshell bio-fillers on the dual-phase fire-retardancy of intumescent coatings applied on cellulosic substrates.

Cellulosic substrates, including wood and thatch, have become icons for sustainable architecture and construction, however, they suffer from high flammability because of their inherent cellulosic composition. Current control measures for such hazards include applying intumescent fire-retardant (IFR) coatings that swell and form a char layer upon ignition, protecting the underlying substrate from burning. Typically, conventional IFR coatings are opaque and are made of halogenated compounds that release toxic fumes when ignited, compromising the roofing's aesthetic value and sustainability. In this work, phytic acid, a naturally occurring phosphorus source extracted from rice bran, was used to synthesize phytic acid-based fire-retardants (PFR) via esterification under reflux, along with powdered chicken eggshells (CES) as calcium carbonate (CaCO3) bio-filler. These components were incorporated into melamine formaldehyde resin to produce the transparent IFR coating. It was revealed that the developed IFR coatings achieved the highest fire protection rating based on UL94 flammability standards compared to the control. The coatings also yielded increased LOI values, indicative of self-extinguishing properties. A 17 °C elevation of the IFR coating's melting temperature and a significant ∼172% increase in enthalpy change from the control were observed, indicating enhanced fire-retardancy. The thermal stability of the coatings was improved, denoted by reduced mass losses, and increased residual masses after thermal degradation. As validated by microscopy and spectroscopy, the abundance of phosphorus and carbon groups in the coatings' condensed phase after combustion indicates enhanced char formation. In the gas phase, TG-FTIR showed the evolution of non-flammable CO2, and fire-retardant PO and P-O-C. Mechanical property testing confirmed no reduction in the adhesion strength of the IFR coating. With these results, the developed IFR coating exhibited enhanced fire-retardancy whilst remaining optically transparent, suggestive of a dual-phase IFR protective mechanism involving the release of gaseous combustion diluents and the formation of a thermally insulating char layer.

Behavioral therapies targeting reward mechanisms in substance use disorders.

Behavioral therapies are considered best practices in the treatment of substance use disorders (SUD) and used as first-line approaches for SUDs without FDA-approved pharmacotherapies. Decades of research on the neuroscience of drug reward and addiction have informed the development of current leading behavioral therapies that, while differing in focus and technique, have in common the overarching goal of shifting reward responding away from drug and toward natural non-drug rewards. This review begins by describing key neurobiological processes of reward in addiction, followed by a description of how various behavioral therapies address specific reward processes. Based on this review, a conceptual 'map' is crafted to pinpoint gaps and areas of overlap, serving as a guide for selecting and integrating behavioral therapies.

Virome release of an invasive exotic plant species in southern France.

The increase in human-mediated introduction of plant species to new regions has resulted in a rise of invasive exotic plant species (IEPS) that has had significant effects on biodiversity and ecosystem processes. One commonly accepted mechanism of invasions is that proposed by the enemy release hypothesis (ERH), which states that IEPS free from their native herbivores and natural enemies in new environments can outcompete indigenous species and become invasive. We here propose the virome release hypothesis (VRH) as a virus-centered variant of the conventional ERH that is only focused on enemies. The VRH predicts that vertically transmitted plant-associated viruses (PAV, encompassing phytoviruses and mycoviruses) should be co-introduced during the dissemination of the IEPS, while horizontally transmitted PAV of IEPS should be left behind or should not be locally transmitted in the introduced area due to a maladaptation of local vectors. To document the VRH, virome richness and composition as well as PAV prevalence, co-infection, host range, and transmission modes were compared between indigenous plant species and an invasive grass, cane bluestem (Bothriochloa barbinodis), in both its introduced range (southern France) and one area of its native range (Sonoran Desert, Arizona, USA). Contrary to the VRH, we show that invasive populations of B. barbinodis in France were not associated with a lower PAV prevalence or richness than native populations of B. barbinodis from the USA. However, comparison of virome compositions and network analyses further revealed more diverse and complex plant-virus interactions in the French ecosystem, with a significant richness of mycoviruses. Setting mycoviruses apart, only one putatively vertically transmitted phytovirus (belonging to the Amalgaviridae family) and one putatively horizontally transmitted phytovirus (belonging to the Geminiviridae family) were identified from B. barbinodis plants in the introduced area. Collectively, these characteristics of the B. barbinodis-associated PAV community in southern France suggest that a virome release phase may have immediately followed the introduction of B. barbinodis to France in the 1960s or 1970s, and that, since then, the invasive populations of this IEPS have already transitioned out of this virome release phase, and have started interacting with several local mycoviruses and a few local plant viruses.

Toxicologic Pathology Forum Opinion: Apoptosis/Single Cell Necrosis as a Possible Procedural Effect in Primate Brain Following Ice-Cold Saline Perfusion.

Nonclinical studies of test articles (TAs) in nonhuman primates are often designed to assess both biodistribution and toxicity. For this purpose, studies commonly use intravenous perfusion of ice-cold (2°C-8°C) saline to facilitate measurements of TA-associated nucleic acids and proteins, after which tissues undergo later fixation by immersion for histological processing and microscopic evaluation. Intriguingly, minimal apoptosis/single cell necrosis (A/SCN) of randomly distributed neural cells is evident in the cerebral cortex and less often the hippocampus in animals from all groups, including vehicle-treated controls. Affected cells exhibit end-stage features such as cytoplasmic hypereosinophilia, nuclear condensation or fragmentation, and shape distortions, so their lineage(s) generally cannot be defined; classical apoptotic bodies are exceedingly rare. In addition, A/SCN is not accompanied by glial reactions, leukocyte infiltration/inflammation, or other parenchymal changes. The severity is minimal in controls but may be slightly exacerbated (to mild) by TA that accumulate in neural cells. One plausible hypothesis explaining this A/SCN exacerbation is that cold shock (perhaps complicated by concurrent tissue acidity and hypoxia) drives still-viable but TA-stressed cells to launch a self-directed death program. Taken together, these observations indicate that A/SCN in brain processed by cold saline perfusion with delayed immersion fixation represents a procedural artifact and not a TA-related lesion.

Prevalence of micronutrient inadequacy differs by severity of food insecurity among adults living in Canada in 2015.

Household food insecurity is generally associated with poorer quality diets in Canada, but whether household food insecurity heightens the probability of inadequate micronutrient intakes is unknown. The objective of this research was to investigate how prevalence of micronutrient inadequacy differed by severity of household food insecurity among adults in Canada. Using the 2015 Canadian Community Health Survey Nutrition, this study included participants aged 19-64 years who completed up to two 24-hour dietary recalls and provided details about household food insecurity (n = 9486). Children and older adults were not included due to sample size limitations. Usual micronutrient intake distributions were estimated by a 4-level measure of food insecurity status using the National Cancer Institute method. Welch's t-tests assessed differences in prevalence of inadequacy for selected micronutrients. Prevalence differed for some micronutrients among those living in marginally and moderately food insecure compared to food secure households. The greatest differences in prevalence of inadequacy were observed between severely food insecure and food secure households: vitamin A (60.0%, SE=11.9 vs. 40.6%, SE=2.7, p<0.0001), vitamin B6 (42.7%, SE=9.1 vs. 12.8%, SE=2.5, p<0.0001), folate (39.4%, SE=10.0 vs. 15.9%, SE=2.2, p<0.0001), vitamin C (63.3%, SE=5.2 vs. 29.1%, SE=2.8, p<0.0001), calcium (78.6%, SE=6.4 vs. 58.7%, SE=1.3, p<0.0001), magnesium (75.6%, SE=9.5 vs. 48.7%, SE=1.2, p<0.0001), and zinc (34.9%, SE=10.0 vs. 23.2%, SE=2.4, p=0.0009). Apparent underreporting also differed by severity of food insecurity, with increased underreporting observed with worsening food insecurity. The probability of inadequate micronutrient intakes among adults rises sharply with more severe household food insecurity in Canada.

White-nose syndrome, winter duration, and pre-hibernation climate impact abundance of reproductive female bats.

White-nose syndrome (WNS) is an infectious disease that disrupts hibernation in bats, leading to premature exhaustion of fat stores. Though we know WNS does impact reproduction in hibernating female bats, we are unsure how these impacts are exacerbated by local climate factors. We compiled data from four southeastern U.S. states and used generalized linear mixed effects models to compare effects of WNS, pre-hibernation climate variables, and winter duration on the number of reproductive females in species across the range of WNS susceptibility. We predicted we would see a decline in the number of reproductive females in WNS-susceptible species, with the effect exaggerated by longer winter durations and pre-hibernation climate variables that lead to reductions in foraging. We found that the number of reproductive females in WNS-susceptible species was positively correlated with pre-hibernation local climate conditions conducive to foraging; however, WNS-susceptible species experienced an overall decline with the presence of WNS and as winter duration increased. Our long-term dataset provides evidence that pre-hibernation climate, specifically favorable summer weather conditions for foraging, greatly influences the reproduction, regardless of WNS status.

Developing competency of nursing students in cardiopulmonary resuscitation using Resuscitation Quality Improvement technology.

OBJECTIVES: This study examined the outcomes of training nursing students in CPR skills using the Resuscitation Quality Improvement (RQI) program. METHODS: Nursing students (n=2,193) in 12 schools across the United States participated in this study. Students performed compressions and bag-masked ventilation on adult and infant manikins using the RQI simulation station without and then with feedback on their performance. RESULTS: With real-time, objective feedback from the RQI simulation station, students' performance of CPR skills improved, and they retained their skills over time. CONCLUSIONS: The RQI program and methodology of feedback is effective for training nursing students to be competent in CPR skills, essential for safe patient care. Nursing and other healthcare professions programs should consider adopting the RQI program for students to develop competency in CPR.

Assessing the effect of soil cultivation methods and genotypes on crop yield components, yield and soil properties in wheat (Triticum aestivum L.) and Rice (Oryza sativa L.) cropping system.

BACKGROUND: The rice-wheat cropping system is the prevailing agricultural method in the North-Western states of India, namely in the Indo-Gangetic plains. The practice of open burning of rice residue is frequently employed for expedient land preparation, but it has significant adverse impacts on both the environment and human health. These include the emission of greenhouse gases, loss of nutrients, elevated concentrations of particulate matter (PM), and disruption of the biological cycle. This research aims to investigate the implementation of effective management strategies in the rice-wheat cropping system, namely via the use of tillage-based crop cultivation techniques, stubble retention, and integration approaches. The objective is to enhance soil health features in order to augment crop yield and improve its attributes. RESULTS: The research was carried out using a split plot experimental design, consisting of three replications. The main plot consisted of four different cultivation methods, while the subplot included three genotypes of both rice and wheat. The research demonstrates the enhanced efficacy of residue application is significantly augmenting soil nutrient concentrations compared to standard tillage practices (P < 0.05). This was accomplished by an analysis of soil nutrient levels, namely nitrogen (N), phosphorus (P), potassium (K), and organic carbon (OC), at a depth of 0-15 cm. The implementation of natural farming, zero tillage, and reduced tillage practices resulted in decreases in rice grain yields of 34.0%, 16.1%, and 10.8%, respectively, as compared to conventional tillage methods. Similarly, the implementation of natural farming, zero tillage, and reduced tillage resulted in reductions in wheat grain yields of 59.4%, 10.9%, and 4.6% respectively, in comparison to conventional tillage practices. CONCLUSION: Regarding the individual crop genotypes investigated, it was continuously observed that Him Palam Lal Dhan 1 and HPW 368 displayed considerably greater grain yields for both rice and wheat during the two-year experimental period. Furthermore, when considering different cultivation methods, conventional tillage emerged as the most effective approach for obtaining higher productivity in both rice and wheat. Additionally, Him Palam Lal Dhan 1 and HPW 368 exhibited superior performance in terms of various crucial yield components for rice (such as panicle density, grains per panicle, panicle weight, and test weight) and wheat (including effective tiller density, grains per spike, spike weight, and 1000-grain weight).

Paradoxical effects of nanomaterials on plants: Phytohormonal perspective exposes hidden risks amidst potential benefits.

The rapid growth of nanotechnology has led to the production of a significant amount of engineered nanomaterials (NMs), raising concerns about their impact on various domains. This study investigates the negative interactions between NMs and phytohormones in plants, revealing the changes in signaling crosstalk, integrated responses and ecological repercussions caused by NM pollution. Phytohormones, which include auxins, cytokinins, gibberellins, abscisic acid, ethylene, jasmonic acid, salicylic acid and brassinosteroids are essential for plant growth, development, and stress responses. This review examines the intricate relationships between NMs and phytohormones, highlighting disruptions in signaling crosstalk, integrated responses, and ecological consequences in plants due to NM pollution. Various studies demonstrate that exposure to NMs can lead to alterations in gene expression, enzyme functions, and ultimately affect plant growth and stress tolerance. Exposure to NMs has the capacity to affect plant phytohormone reactions by changing their levels, biosynthesis, and signaling mechanisms, indicating a complex interrelation between NMs and phytohormone pathways. The complexity of the relationships between NMs and phytohormones necessitates further research, utilizing modern molecular techniques, to unravel the intricate molecular mechanisms and develop strategies to mitigate the ecological consequences of NM pollution. This review provides valuable insights for researchers and environmentalists concerned about the disruptive effects of NMs on regulating phytohormone networks in plants.

Opioid Risk Tool, in-hospital opioid exposure, and opioid demand predict pain outcomes following traumatic injury.

Prescribed opioids are a mainstay pain treatment after traumatic injury, but a subgroup of patients may be at risk for continued opioid use. We evaluated the predictive utility of a traditional screening tool, the Opioid Risk Tool (ORT), and two other measures: average in-hospital milligram morphine equivalents (MME) per day and an assessment of opioid demand in predicting pain outcomes. Assessments of pain-related outcomes (pain intensity, interference, injury-related stress, and need for additional pain treatment) were administered at 2 weeks and 12 months post-discharge in a sample of 34 patients hospitalized for traumatic injury. Bayesian linear models were used to evaluate changes in responses over time as a function of predictors. High-risk ORT, higher MME per day, and greater opioid demand predicted less change in outcomes over time. This report provides first evidence that malleable factors of opioid and opioid demand have utility in predicting pain outcomes following traumatic injury.

Long-term disease-free survival with chemotherapy and pembrolizumab in a patient with unmeasurable, advanced stage dedifferentiated endometrial carcinoma.

Dedifferentiated endometrial carcinoma is a rare, highly aggressive subtype of endometrial cancer associated with poor survival outcomes. Current guidelines recommend treatment of advanced-stage disease with surgical staging or cytoreduction and platinum/taxane-based chemotherapy. Despite these approaches, the achievement of long-term remission or prolonged survival is challenging. Recent Phase III studies demonstrate that the addition of PD-1 inhibitors to standard chemotherapy significantly improves progression-free survival in patients with measurable, mismatch repair deficient (dMMR) and proficient (pMMR) advanced-stage or recurrent endometrial carcinoma. However, the role of PD-1 blockade in the treatment of undifferentiated and dedifferentiated endometrial carcinoma remains unclear, as very few patients with these cancer subtypes were included in the trials. In this case report, we present a patient with dMMR dedifferentiated endometrial carcinoma, treated with primary surgery to no gross residual disease, followed by carboplatin/paclitaxel chemotherapy and a short course of maintenance pembrolizumab. To date, the patient remains with a prolonged disease-free survival of 61 months, supporting the potential use of PD-1 inhibitors in the upfront treatment of unmeasurable, advanced-stage, dMMR dedifferentiated endometrial carcinoma.

Tissues and signals with true organizer properties in craniofacial development.

Transplantation experiments have shown that a true organizer provides instructive signals that induce and pattern ectopic structures in the responding tissue. Here, we review craniofacial experiments to identify tissues with organizer properties and signals with organizer properties. In particular, we evaluate whether transformation of identity took place in the mesenchyme. Using these stringent criteria, we find the strongest evidence for the avian foregut ectoderm. Transplanting a piece of quail foregut endoderm to a host chicken embryo caused ectopic beaks to form derived from chicken mesenchyme. The beak identity, whether upper or lower as well as orientation, was controlled by the original anterior-posterior position of the donor endoderm. There is also good evidence that the nasal pit is necessary and sufficient for lateral nasal patterning. Finally, we review signals that have organizer properties on their own without the need for tissue transplants. Mouse germline knockouts of the endothelin pathway result in transformation of identity of the mandible into a maxilla. Application of noggin-soaked beads to post-migratory neural crest cells transforms maxillary identity. This suggests that endothelin or noggin rich ectoderm could be organizers (not tested). In conclusion, craniofacial, neural crest-derived mesenchyme is competent to respond to tissues with organizer properties, also originating in the head. In future, we can exploit such well defined systems to dissect the molecular changes that ultimately lead to patterning of the upper and lower jaw.

Diverse papillomaviruses identified from Antarctic fur seals, leopard seals and Weddell seals from the Antarctic.

Papillomaviruses (family Papillomaviridae) are non-enveloped, circular, double-stranded DNA viruses known to infect squamous and mucosal epithelial cells. In the family Papillomaviridae there are 53 genera and 133 viral species whose members infect a variety of mammalian, avian, reptilian, and fish species. Within the Antarctic context, papillomaviruses (PVs) have been identified in Adélie penguins (Pygoscelis adeliae, 2 PVs), Weddell seals (Leptonychotes weddellii, 7 PVs), and emerald notothen (Trematomus bernacchii, 1 PV) in McMurdo Sound and Ross Island in eastern Antarctica. Here we identified 13 diverse PVs from buccal swabs of Antarctic fur seals (Arctocephalus gazella, 2 PVs) and leopard seal (Hydrurga leptonyx, 3 PVs) in western Antarctica (Antarctic Peninsula), and vaginal and nasal swabs of Weddell seals (8 PVs) in McMurdo Sound. These PV genomes group into four genera representing 11 new papillomavirus types, of which five are from two Antarctic fur seals and a leopard seal and six from Weddell seals.

Draft genome sequences of Arthrobacter sp. AZCC_0090 and Mycobacterium sp. AZCC_0083 isolated from oligotrophic subsurface forest soil in the Santa Catalina mountains of Southern Arizona.

Here, we present the genomes of two soil actinobacteria: Arthrobacter sp. strain AZCC_0090 and Mycobacterium sp. strain AZCC_0083, isolated from oligotrophic subsurface soils in Southern Arizona, USA.

Flexible Polyurethane Foams Modified with Novel Coconut Monoglycerides-Based Polyester Polyols.

Coconut oil, a low-molecular-weight vegetable oil, is virtually unutilized as a polyol material for flexible polyurethane foam (FPUF) production due to the high-molecular-weight polyol requirement of FPUFs. The saturated chemistry of coconut oil also limits its compatibility with widely used polyol-forming processes, which mostly rely on the unsaturation of vegetable oil for functionalization. Existing studies have only exploited this resource in producing low-molecular-weight polyols for rigid foam synthesis. In this present work, high-molecular-weight polyester polyols were synthesized from coconut monoglycerides (CMG), a coproduct of fatty acid production from coconut oil, via polycondensation at different mass ratios of CMG with 1:5 glycerol:phthalic anhydride. Characterization of the CMG-based polyol (CMGPOL) products showed number-average molecular weights between 1997 and 4275 g/mol, OH numbers between 77 and 142 mg KOH/g, average functionality between 4.8 and 5.8, acid numbers between 4.49 and 23.56 mg KOH/g, and viscosities between 1.27 and 89.57 Pa·s. The polyols were used to synthesize the CMGPOL-modified PU foams (CPFs) at 20 wt % loading. The modification of the foam formulation increased the monodentate and bidentate urea groups, shown using Fourier transform infrared (FTIR) spectroscopy, that promoted microphase separation in the foam matrix, confirmed using atomic force microscopy (AFM) and differential scanning calorimetry (DSC). The implications of the structural change to foam morphology and open cell content were investigated using a scanning electron microscope (SEM) and gas pycnometer. The density of the CPFs decreased, while a significant improvement in their tensile and compressive properties was observed. Also, the CPFs exhibited different resiliency with a correlation to microphase separation. These findings offer a new sustainable polyol raw material that can be used to modify petroleum-based foam and produce flexible foams with varying properties that can be tailored to meet specific requirements.

Sexual dichromatism in the fur of a bat: An exploration of color differences and potential signaling functions.

Sex differences in body color (i.e., sexual dichromatism) are rare in bats and, more broadly, in mammals. The eastern red bat (Lasiurus borealis) is a common tree-roosting bat that occupies much of North America and has long been described as sexually dichromatic. However, previous research on this species found that absolute body size and collection year were better predictors of fur color in preserved specimens than sex. We revisited this issue and photographed 82 live eastern red bats under standardized conditions, then used image analysis to quantify pelage hue, saturation, and value. We used an information theoretic approach to evaluate four competing hypotheses about the principal drivers of color differences in the fur of eastern red bats. Our analyses demonstrated that sex was a better predictor of pelage color than body size; males had redder, more saturated, and lighter pelages than females. Additionally, the fur color of juvenile versus adult bats differed somewhat, as juveniles were darker than adults. In general, absolute body size (i.e., forearm length in bats) was a poor predictor of color in live eastern red bats. In an exploratory post-hoc analysis, we confirm that fur color is related to body mass (i.e., a proxy for body condition in bats), suggesting color might serve as a sexually selected signal of mate quality in this partially diurnal species. Future work should investigate the functional role of sexual dichromatism in this species, which could be related to signaling or possibly thermoregulation.

Acoustic monitoring yields informative bat population density estimates.

Bat population estimates are typically made during winter, although this is only feasible for bats that aggregate in hibernacula. While it is essential to measure summer bat population sizes for management, we lack a reliable method. Acoustic surveys should be less expensive and more efficient than capture surveys, and acoustic activity data are already used as indices of population size. Although we currently cannot differentiate individual bats by their calls, we can enter call counts, information on signal and detection angles, and weather data into generalized random encounter models to estimate bat density. We assessed the utility of generalized random encounter models for estimating Indiana bat (Myotis sodalis) population density with acoustic data collected at 51 total sites in six conservation areas in northeast Missouri, 2019-2021. We tested the effects of year, volancy period, conservation area, and their interactions on estimated density. Volancy period was the best predictor, with average predicted density increasing 60% from pre-volancy (46 bats/km2) to post-volancy (74 bats/km2); however, the magnitude of the effect differed by conservation area. We showed that passive acoustic surveys yield informative density estimates that are responsive to temporal changes in bat population size, which suggests this method may be useful for long-term monitoring. However, we need more information to choose the most appropriate values for the density estimation formula. Future work to refine this approach should include assessments of bat behavior and detection parameters and testing the method's efficacy in areas where population sizes are known.

Contingency management plus acceptance and commitment therapy for initial cocaine abstinence: Results of a sequential multiple assignment randomized trial (SMART).

BACKGROUND: This study tested an adaptive intervention for optimizing abstinence outcomes over phases of treatment for cocaine use disorder using a SMART design. Phase 1 assessed whether 4 weeks of contingency management (CM) improved response with the addition of Acceptance and Commitment Therapy (ACT). Phase 2 assessed pharmacological augmentation with modafinil (MOD) vs. placebo (PLA) for individuals not achieving abstinence during Phase 1. METHOD: For Phase 1 of treatment, participants (N=118) were randomly allocated to ACT+CM or Drug Counseling (DC+CM), the comparison condition. At week 4, treatment response was defined as the submission of six consecutive cocaine-negative urine drug screens (UDS). Phase 1 non-responders were re-randomized to MOD or PLA as adjunct to their initial treatment. Phase 1 responders continued receiving their initial treatment. Primary outcomes included response rate and proportion of cocaine-negative UDS for Phase 1 and 2. Analyses used Bayesian inference with 80% pre-specified as the posterior probability (PP) threshold constituting moderate evidence that an effect exists. RESULTS: Phase 1 response was higher in the ACT+CM group (24.5%) compared to the DC+CM group (17.5%; PP = 84.5%). In Phase 2, the proportion of cocaine-negative UDS among Phase 1 responders did not differ by initial treatment (PP = 61.8%) but remained higher overall compared to Phase 1 non-responders (PPs > 99%). No evidence of an effect favoring augmentation with MOD was observed. DISCUSSION: Adding ACT to CM increased abstinence initiation. Initial responders were more likely to remain abstinent compared to initial non-responders, for whom modafinil was not an effective pharmacotherapy augmentation strategy.

Crystal structure and biophysical characterization of IspD from Burkholderia thailandensis and Mycobacterium paratuberculosis.

The methylerythritol phosphate (MEP) pathway is a metabolic pathway that produces the isoprenoids isopentyl pyrophosphate and dimethylallyl pyrophosphate. Notably, the MEP pathway is present in bacteria and not in mammals, which makes the enzymes of the MEP pathway attractive targets for discovering new anti-infective agents due to the reduced chances of off-target interactions leading to side effects. There are seven enzymes in the MEP pathway, the third of which is IspD. Two crystal structures of Burkholderia thailandensis IspD (BtIspD) were determined: an apo structure and that of a complex with cytidine triphosphate (CTP). Comparison of the CTP-bound BtIspD structure with the apo structure revealed that CTP binding stabilizes the loop composed of residues 13-19. The apo structure of Mycobacterium paratuberculosis IspD (MpIspD) is also reported. The melting temperatures of MpIspD and BtIspD were evaluated by circular dichroism. The moderate Tm values suggest that a thermal shift assay may be feasible for future inhibitor screening. Finally, the binding affinity of CTP for BtIspD was evaluated by isothermal titration calorimetry. These structural and biophysical data will aid in the discovery of IspD inhibitors.

A meta-analysis of electrophysiological biomarkers of reward and error monitoring in substance misuse.

Substance use disorders are characterized by marked changes in reward and error processing. The primary objective of this meta-analysis was to estimate effect sizes for the reward positivity (RewP) and error-related negativity (ERN), two event-related potential indicators of outcome monitoring, in substance users compared to controls. The secondary objective was to test for moderation by demographic, substance type, and EEG experiment parameters. Final PubMed searches were performed in August 2023. Inclusion criteria were substance use disorder/dependence or validated self-report of substance misuse, RewP/ERN means available, healthy control comparison group, non-acute drug study, peer-reviewed journal, English language, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. The RewP results (19 studies, 1641 participants) did not support an overall effect (Hedges' g = 0.07, 95% CI [-0.44, 0.58], p = .777) and nor effect of any moderators. The ERN results (20 studies, 1022 participants) indicated no significant overall effect (g = 0.41, 95%CI [-0.05, 0.88]). Subgroup analyses indicated that cocaine users had a blunted ERN compared to controls (g = 1.12, 95%CI [0.77, 1.47]). There was limited evidence for publication/small study bias. Although the results indicate a potential dissociation between substance types, this meta-analysis revealed the need for additional research on the RewP/ERN in substance using populations and for better designed experiments that adequately address research questions.