Surgical Management of Iatrogenic Mercury Poisoning From Subcutaneous Injection Into the Arm.

BACKGROUND: Mercury, an element with threats of severe toxic insult to humans and no biological function, has a surprisingly extensive record of human exposure. Regardless of hesitancies toward its harmfulness, it has been historically identified with an almost supernatural power to provide protection from evil and sickness, give good fortune, lend aid in athletic undertakings, or even allow one to achieve immortality. Mercury poisoning is an iatrogenic disease even today as people attempt to achieve these effects through volitional injections into their body by practitioners. Although an uncommon practice in the United States, awareness of patient presentation after volitional injections of elemental mercury is necessary for appropriate treatment of these patients. We aim to increase awareness of the cultural practice of subcutaneous injections of mercury, as it is uncommonly seen in the United States, to contribute a broader understanding to the patient's medical presentation and describe an approach and the impact of medical and surgical intervention. METHODS: In this report, we describe a rare case of elemental mercury poisoning secondary to volitional subcutaneous injection to the arm. Initial management of care through chelation therapy and monitoring of renal and serum mercury levels in addition to symptoms of systemic spread was overseen by an internal medicine physician and poison control. Surgical intervention via full-thickness excision of the visible mercury to the right arm followed by local flap and skin grafting reconstruction was performed. CONCLUSIONS: Mercury poisoning from intentional subcutaneous administration is an uncommon patient presentation in the United States; however, knowledge of management of this rare condition is important for effective management of iatrogenic mercury toxicity.

Selection of den sites and chronology of denning by black bears in the eastern Sierra Nevada and western Great Basin.

Use of dens during winter is an important strategy for American black bears (Ursus americanus) for both energy conservation and reproduction; and occupancy of suitable den sites has implications for reproductive fitness. Denning strategies may change as a result of changing climatic conditions and habitat loss. Black bears occupy arid environments in the eastern Sierra Nevada and the western ranges of the Great Basin Ecosystem. Our objectives were to identify: (1) which physical characteristics of habitat influenced selection of den sites at multiple spatial scales and (2) which environmental factors influenced timing of entrance and exit of dens by females and males. We evaluated selection of den sites by black bears at three spatial scales (300, 1000, and 4000 m) from 2011 to 2022. Terrain ruggedness was important for selection of den sites at all spatial scales. Within a 300-m buffer from the den, bears selected den sites with rugged terrain, lower horizontal visibility, and greater canopy cover, resulting in more concealment and protection than that of the surrounding environment. Within 1000- and 4000-m buffers around each den, bears selected den sites with rugged terrain, northern aspects, and steep slopes. At the 4000-m scale, we observed interactions between sex with slope and distance to roads; females selected den sites on steeper slopes and closer to roads than did males. Females remained in the dens longer than males by entering earlier in the autumn and exiting later in the spring. Male bears exited their dens earlier with increasing consecutive days above freezing temperatures, but that relationship was weak for females. Knowing what characteristics are important for selection of den sites, and influence timing of denning, will be important for understanding how shifting climatic patterns will affect bears, particularly in arid environments that may be prone to wider fluctuations in climatic drivers of denning in the future.

Liquid-assisted grinding enables a direct mechanochemical functionalization of polystyrene waste.

The plastic waste crisis has grave consequences for our environment, as most single-use commodity polymers remain in landfills and oceans long after their commercial lifetimes. Utilizing modern synthetic techniques to chemically modify the structure of these post-consumer plastics (e.g., upcycling) can impart new properties and added value for commercial applications. To expand beyond the abilities of current solution-state chemical processes, we demonstrate post-polymerization modification of polystyrene via solid-state mechanochemistry enabled by liquid-assisted grinding (LAG). Importantly, this emblematic trifluoromethylation study modifies discarded plastic, including dyed materials, using minimal exogenous solvent and plasticizers for improved sustainability. Ultimately, this work serves as a proof-of-concept for the direct mechanochemical post-polymerization modification of commodity polymers, and we expect future remediation of plastic waste via similar mechanochemical reactions.

Understanding learners' experiences across three major transitions in undergraduate medical education.

BACKGROUND: Medical students in the United States undergo three significant transitions as they progress from pre-clinical to clinical rotations, to acting interns, and ultimately to first-year resident. However, there is limited understanding of whether the factors and strategies that impact these transitions remain consistent or are unique to each individual transition. METHODS: Qualitative data was collected from three Nominal Group Technique (NGT) sessions held separately for third-year students (M3), fourth-year students (M4), and first-year residents (PGY-1). The participants were asked to share their perceptions on their most recent medical school transition. These responses were independently coded into thematic categories. RESULTS: The NGT session with M3 students (n = 9) identified 67 transition factors and 64 coping strategies. The M4 (n = 8) session identified 33 transition factors and 72 strategies to manage their transition. The PGY-1 (n = 5) session identified 28 factors and 25 strategies. The coping strategies for each session were categorized into seven themes and the transition factors were assigned to ten thematic categories. CONCLUSION: Just as each transition is unique, so too are the number and variety of factors and strategies to manage each transition. Despite these differences, the themes of "Professional socialization" and "Prioritization, efficiency, and delegation" emerged as impactful in all three transitions.

Reelin marks cocaine-activated striatal ensembles, promotes neuronal excitability, and regulates cocaine reward.

Drugs of abuse activate defined neuronal ensembles in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote the enduring synaptic, circuit, and behavioral consequences of drug exposure. While the molecular and cellular effects arising from experience with drugs like cocaine are increasingly well understood, the mechanisms that sculpt NAc ensemble participation are largely unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling to identify expression of the secreted glycoprotein Reelin (encoded by the Reln gene) as a marker of cocaine-activated neuronal ensembles within the rat NAc. Multiplexed in situ detection confirmed selective expression of the immediate early gene Fos in Reln+ neurons after cocaine experience, and also revealed enrichment of Reln mRNA in Drd1 + medium spiny neurons (MSNs) in both the rat and human brain. Using a novel CRISPR interference strategy enabling selective Reln knockdown in the adult NAc, we observed altered expression of genes linked to calcium signaling, emergence of a transcriptional trajectory consistent with loss of cocaine sensitivity, and a striking decrease in MSN intrinsic excitability. At the behavioral level, loss of Reln prevented cocaine locomotor sensitization, abolished cocaine place preference memory, and decreased cocaine self-administration behavior. Together, these results identify Reelin as a critical mechanistic link between ensemble participation and cocaine-induced behavioral adaptations.

Plasma proteomic comparisons change as coverage expands for SomaLogic and Olink.

The number of assays on highly-multiplexed proteomic platforms has grown ten-fold over the past 15 years from less than 1,000 to >11,000. The leading aptamer-based and antibody-based platforms have different strengths. For example, Eldjarn et al 1 demonstrated that the aptamer-based SomaScan 5k (4,907 assays, assessed in the Icelandic 36K) and the antibody-based Olink Explore 3072 (2,931 assays, assessed in the UK BioBank) had a similar number of cis -pQTLs among all targets (2,120 vs. 2,101) but Olink had a greater number of cis -pQTLs among the overlapping targets (1,164 vs. 1,467). Analysis of split plasma measures showed the SomaScan assays to be more precise: median coefficient of variation (CV) of 9.9% vs. 16.5% for Olink. 1 Precision of the newest versions of the platforms-SomaScan 11k (>11,000 assays, released in December 2023) and Olink Explore HT (>5,400 assays, released in July 2023)-has not yet been established. We assessed the reproducibility of the SomaScan 11k and Olink Explore HT using split plasma samples from 102 Atherosclerosis Risk in Communities (ARIC) Study participants. We found that the SomaScan 11k assays had a median CV of 6.8% (vs 6.6% for the subset of assays available on the SomaScan 5k) and the Olink Explore HT assays had a median CV of 35.7% (vs 19.8% for the subset of assays available on the Olink Explore 3072). Across Olink assays, the CVs were strongly negatively correlated with protein detectability, i.e., percent of samples above the limit of detection (LOD). For the 4,443 overlapping assays, the distribution of between-platform correlations was bimodal with a peak at r ∼0 and with another smaller peak at r ∼0.8. These findings on precision are consistent with the updated results by Eldjarn et al 1 but indicate that precision of these two leading platforms in human plasma has diverged as the number of included proteins has increased.

Plasma proteins associated with plant-based diets: Results from the Atherosclerosis Risk in Communities (ARIC) study and Framingham Heart Study (FHS).

BACKGROUND & AIMS: Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort. METHODS: ARIC Study participants at visit 3 (1993-1995) with completed food frequency questionnaire (FFQ) data and proteomics data were divided into internal discovery (n = 7690) and replication (n = 2543) data sets. Multivariable linear regression was used to examine associations between plant-based diet indices (PDIs) and 4955 individual proteins in the discovery sample. Then, proteins that were internally replicated in the ARIC Study were tested for external replication in FHS (n = 1358). Pathway overrepresentation analysis was conducted for diet-related proteins. C-statistics were used to predict if the proteins improved prediction of plant-based diet indices beyond participant characteristics. RESULTS: In ARIC discovery, a total of 837 diet-protein associations (PDI = 233; provegetarian = 182; hPDI = 406; uPDI = 16) were observed at false discovery rate (FDR) < 0.05. Of these, 453 diet-protein associations (PDI = 132; provegetarian = 104; hPDI = 208; uPDI = 9) were internally replicated. In FHS, 167/453 diet-protein associations were available for external replication, of which 8 proteins (PDI = 1; provegetarian = 0; hPDI = 8; uPDI = 0) replicated. Complement and coagulation cascades, cell adhesion molecules, and retinol metabolism were over-represented. C-C motif chemokine 25 for PDI and 8 proteins for hPDI modestly but significantly improved the prediction of these indices individually and collectively (P value for difference in C-statistics<0.05 for all tests). CONCLUSIONS: Using large-scale proteomics, we identified potential candidate biomarkers of plant-based diets, and pathways that may partially explain the associations between plant-based diets and chronic conditions.

Estimating coccidioidomycosis endemicity while accounting for imperfect detection using spatio - temporal occupancy modeling.

Coccidioidomycosis, or Valley fever, is an infectious disease caused by inhaling Coccidioides fungal spores. Incidence has risen in recent years, and it is believed the endemic region for Coccidioides is expanding in response to climate change. While Valley fever case data can help us understand trends in disease risk, using case data as a proxy for Coccidioides endemicity is not ideal because case data suffers from imperfect detection, including false positives (e.g., travel-related cases reported outside of endemic area) and false negatives (e.g., misdiagnosis or underreporting). We proposed a Bayesian, spatio-temporal occupancy model to relate monthly, county-level presence/absence data on Valley fever cases to latent endemicity of Coccidioides, accounting for imperfect detection. We used our model to estimate endemicity in the western United States. We estimated high probability of endemicity in southern California, Arizona, and New Mexico, but also in regions without mandated reporting, including western Texas, eastern Colorado, and southeastern Washington. We also quantified spatio-temporal variability in detectability of Valley fever, given an area is endemic to Coccidioides. We estimated an inverse relationship between lagged 3- and 9-month precipitation and case detection, and a positive association with agriculture. This work can help inform public health surveillance needs and identify areas that would benefit from mandatory case reporting.

Growth and population structure of Lodoicea maldivica in natural stands in Seychelles.

We monitored leaf production in seedlings, trunkless juvenile, immature, and mature male and female plants of the dioecious palm, Lodoicea maldivica, and studied how internode length changed with trunk height. The fieldwork was conducted in closed forest on Praslin Island and degraded forest on Curieuse Island. Data on numbers of leaves produced and rates of leaf production were used to estimate plant age. On Praslin, the interval between successive leaves increased from 0.47/0.52 years in male/female plants to 4.2 years in seedlings, and on Curieuse from 0.41/0.49 to 2.3 years. Estimated leaf lifespan was 6.4-6.8 years in mature palms and much longer in seedlings and juveniles. On Praslin, internode length increased from the base of the trunk to a mean of 14 cm at leaf 21, before declining to 2.75 cm above leaf 100. Mean internode length of the smaller palms on Curieuse was 1.9 cm and varied little with height. Plants at the same development stage varied widely in age. On Praslin, median time to maturity was 77 (range: 32-209) and on Curieuse 83 (31-191) years. The tallest palms on Praslin (28.4 m trunk height) and Curieuse (8 m) were estimated at 442 and 232 years old, respectively. The ageing method was used to interpret height data of different populations. All showed a marked decline in regeneration in the 19th or early 20th centuries, probably caused by fires. We conclude that slow growth makes this species very vulnerable to disturbance, especially from fire.

Factors Associated with Time to Initial Antiretroviral Therapy Discontinuation in the DC Cohort.

When an initial antiretroviral therapy (ART) regimen is effective and well-tolerated, it can be maintained for years as long as the patient adheres. Prior research has revealed that shorter initial ART duration is associated with regimen type, female sex, injection drug use as the HIV transmission category, and lower baseline CD4 count. We examined potential factors associated with initial regimen discontinuation among a subset of newly diagnosed virally unsuppressed PWH in the DC Cohort, an ongoing prospective observation study that uses electronic health record data from clinic sites to collect relevant information, including demographic and clinical information. Participants were excluded from the analysis if they had less than 6 months of follow-up and were virally suppressed at enrollment. There were 479 individuals included in the study. The median age of participants was 33.9 years [interquartile range (IQR) 26-43.9]. The sample was predominantly male (79.1%) and of Black race (70.8%). Over half of the study participants (56.4%) attended community-based clinic sites. The median time to the discontinuation of initial ART was 2.7 years [95% confidence interval (CI): 2.3, 3.4]. Females had a shorter time to ART discontinuation [adjusted hazard ratio (aHR) 1.55, 95% CI: 1.14, 2.11] as did individuals who started on a protease inhibitor-based regimen versus integrase strand transfer inhibitors (aHR 1.87, 95% CI: 1.34, 2.61) and those receiving HIV care at a community-based site (aHR 1.46, 95% CI: 1.11,1.93). Although limited by lack of reason for discontinuation, we demonstrated that ART-naïve women, community clinic attendees, and patients starting on PIs had a shorter duration of initial ART. More anticipatory guidance may be needed to help patients stay on their initial therapy and manage the side effects or to be flexible in trying different regimens.

Rural and urban differences in marijuana use following passages of medical marijuana laws.

INTRODUCTION: Understanding differences in post-legalization patterns of marijuana between rural and urban environments has the potential to go a long way towards targeting intervention efforts aimed at reducing marijuana use disorders. METHODS: Data come from the National Survey on Drug Use and Health (NSDUH, 2015-2019, N = 210,392). Survey-weighted multivariable linear and logistic regression analyses were used to assess the relationship between key marijuana-related variables and the status of medical marijuana use in each state with interaction terms for rural versus urban status. RESULTS: Among the entire sample, the prevalence of marijuana abuse and dependence were 0.7% and 1.8%, respectively. Among marijuana users, the average number of days on which marijuana was used was 131.3 (SD = 136.3) days. Those living in states with legalized medical marijuana reported use on a greater number of days (B = 10.69; 95% CI: 5.26, 16.13) with frequency of use increasing as rurality increased, compared to a core based statistical area (CBSA) of ≥1 million: a CBSA of <1 million residents (B = 23.02; 95% CI: 17.38, 28.66) and non-CBSA (B = 37.62; 95% CI: 22.66, 52.58). We also observed lower odds of driving under the influence of marijuana in states where medical marijuana was legal (aOR = 0.86; 95% CI: 0.77, 0.95). CONCLUSION: We observed an increase in the frequency of marijuana use and a decrease in driving under the influence of marijuana in states with legalized medical marijuana use relative to those states where it remained illegal. We also observed key moderation based on rural-urban status. This body of results suggests that problematic marijuana use may be on the rise following the legalization of marijuana use, but also that corresponding protective attitudes exist.

Mid-life plasma proteins associated with late-life prefrailty and frailty: a proteomic analysis.

Physical frailty is a syndrome that typically manifests in later life, although the pathogenic process causing physical frailty likely begins decades earlier. To date, few studies have examined the biological signatures in mid-life associated with physical frailty later in life. Among 4,189 middle-aged participants (57.8 ± 5.0 years, 55.8% women) from the Atherosclerosis Risk in Community (ARIC) study, we evaluated the associations of 4,955 plasma proteins (log 2-transformed and standardized) measured using the SomaScan platform with their frailty status approximately 20 years later. Using multinomial logistic regression models adjusting for demographics, health behaviors, kidney function, total cholesterol, and comorbidities, 12 and 221 proteins were associated with prefrailty and frailty in later life, respectively (FDR p < 0.05). Top frailty-associated proteins included neurocan core protein (NCAN, OR = 0.66), fatty acid-binding protein heart (FABP3, OR = 1.62) and adipocyte (FABP4, OR = 1.65), as well proteins involved in the contactin-1 (CNTN1), toll-like receptor 5 (TLR5), and neurogenic locus notch homolog protein 1 (NOTCH1) signaling pathway relevant to skeletal muscle regeneration, myelination, and inflammation. Pathway analyses suggest midlife dysregulation of inflammation, metabolism, extracellular matrix, angiogenesis, and lysosomal autophagy among those at risk for late-life frailty. After further adjusting for midlife body mass index (BMI) - an established frailty risk factor - only CNTN1 (OR = 0.75) remained significantly associated with frailty. Post-hoc analyses demonstrated that the top 41 midlife frailty-associated proteins mediate 32% of the association between mid-life BMI and late-life frailty. Our findings provide new insights into frailty etiology earlier in the life course, enhancing the potential for prevention.

Oncometabolite 2-hydroxyglutarate suppresses basal protein levels of DNA polymerase beta that enhances alkylating agent and PARG inhibition induced cytotoxicity.

Mutations in isocitrate dehydrogenase isoform 1 (IDH1) are primarily found in secondary glioblastoma (GBM) and low-grade glioma but are rare in primary GBM. The standard treatment for GBM includes radiation combined with temozolomide, an alkylating agent. Fortunately, IDH1 mutant gliomas are sensitive to this treatment, resulting in a more favorable prognosis. However, it's estimated that up to 75 % of IDH1 mutant gliomas will progress to WHO grade IV over time and develop resistance to alkylating agents. Therefore, understanding the mechanism(s) by which IDH1 mutant gliomas confer sensitivity to alkylating agents is crucial for developing targeted chemotherapeutic approaches. The base excision repair (BER) pathway is responsible for repairing most base damage induced by alkylating agents. Defects in this pathway can lead to hypersensitivity to these agents due to unresolved DNA damage. The coordinated assembly and disassembly of BER protein complexes are essential for cell survival and for maintaining genomic integrity following alkylating agent exposure. These complexes rely on poly-ADP-ribose formation, an NAD+-dependent post-translational modification synthesized by PARP1 and PARP2 during the BER process. At the lesion site, poly-ADP-ribose facilitates the recruitment of XRCC1. This scaffold protein helps assemble BER proteins like DNA polymerase beta (Polß), a bifunctional DNA polymerase containing both DNA synthesis and 5'-deoxyribose-phosphate lyase (5'dRP lyase) activity. Here, we confirm that IDH1 mutant glioma cells have defective NAD+ metabolism, but still produce sufficient nuclear NAD+ for robust PARP1 activation and BER complex formation in response to DNA damage. However, the overproduction of 2-hydroxyglutarate, an oncometabolite produced by the IDH1 R132H mutant protein, suppresses BER capacity by reducing Polß protein levels. This defines a novel mechanism by which the IDH1 mutation in gliomas confers cellular sensitivity to alkylating agents and to inhibitors of the poly-ADP-ribose glycohydrolase, PARG.

Prevalence and diversity of TAL effector-like proteins in fungal endosymbiotic Mycetohabitans spp.

Endofungal Mycetohabitans (formerly Burkholderia) spp. rely on a type III secretion system to deliver mostly unidentified effector proteins when colonizing their host fungus, Rhizopus microsporus. The one known secreted effector family from Mycetohabitans consists of homologues of transcription activator-like (TAL) effectors, which are used by plant pathogenic Xanthomonas and Ralstonia spp. to activate host genes that promote disease. These 'Burkholderia TAL-like (Btl)' proteins bind corresponding specific DNA sequences in a predictable manner, but their genomic target(s) and impact on transcription in the fungus are unknown. Recent phenotyping of Btl mutants of two Mycetohabitans strains revealed that the single Btl in one Mycetohabitans endofungorum strain enhances fungal membrane stress tolerance, while others in a Mycetohabitans rhizoxinica strain promote bacterial colonization of the fungus. The phenotypic diversity underscores the need to assess the sequence diversity and, given that sequence diversity translates to DNA targeting specificity, the functional diversity of Btl proteins. Using a dual approach to maximize capture of Btl protein sequences for our analysis, we sequenced and assembled nine Mycetohabitans spp. genomes using long-read PacBio technology and also mined available short-read Illumina fungal-bacterial metagenomes. We show that btl genes are present across diverse Mycetohabitans strains from Mucoromycota fungal hosts yet vary in sequences and predicted DNA binding specificity. Phylogenetic analysis revealed distinct clades of Btl proteins and suggested that Mycetohabitans might contain more species than previously recognized. Within our data set, Btl proteins were more conserved across M. rhizoxinica strains than across M. endofungorum, but there was also evidence of greater overall strain diversity within the latter clade. Overall, the results suggest that Btl proteins contribute to bacterial-fungal symbioses in myriad ways.

Extreme Humid-Heat Exposure and Mortality Among Patients Receiving Dialysis.

RATIONALE & OBJECTIVE: Exposure to extreme heat events has been linked to increased morbidity and mortality in the general population. Patients receiving maintenance dialysis may be vulnerable to greater risks from these events, but this is not well understood. We characterized the association of extreme heat events and the risk of death among patients receiving dialysis in the United States. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Data from the US Renal Data System were used to identify adults living in US urban settlements prone to extreme heat who initiated maintenance dialysis between 1997 and 2016. EXPOSURE: An extreme heat event, defined as a time-updated heat index (a humid-heat metric) exceeding 40.6°C for≥2 days or 46.1°C for≥1day. OUTCOME: Death. ANALYTICAL APPROACH: Cox proportional hazards regression to estimate the elevation in risk of death during a humid-heat event adjusted for age, sex, year of dialysis initiation, dialysis modality, poverty level, and climate region. Interactions between humid-heat and these same factors were explored. RESULTS: Among 945,251 adults in 245 urban settlements, the mean age was 63 years, and 44% were female. During a median follow-up period of 3.6 years, 498,049 adults were exposed to at least 1 of 7,154 extreme humid-heat events, and 500,025 deaths occurred. In adjusted models, there was an increased risk of death (hazard ratio 1.18 [95% CI, 1.15-1.20]) during extreme humid-heat exposure. The relative mortality risk was higher among patients living in the Southeast (P<0.001) compared with the Southwest. LIMITATIONS: Possibility of exposure misclassification, did not account for land use and air pollution co-exposures. CONCLUSIONS: This study suggests that patients receiving dialysis face an increased risk of death during extreme humid-heat exposure. PLAIN-LANGUAGE SUMMARY: Patients who receive dialysis are vulnerable to extreme weather events, and rising global temperatures may bring more frequent extreme heat events. We sought to determine whether extreme heat exposure was associated with an increased risk of death in urban-dwelling patients receiving dialysis across the United States. We found that people receiving dialysis were more likely to die during extreme humid-heat events, defined by a heat index exceeding 40.6°C (105°F) for≥2 days or 46.1°C (115°F) for≥1day. These findings inform the nephrology community about the potential importance of protecting patients receiving maintenance dialysis from the risks associated with extreme heat.

The Latent Aging of Cells.

As epigenetic clocks have evolved from powerful estimators of chronological aging to predictors of mortality and disease risk, it begs the question of what role DNA methylation plays in the aging process. We hypothesize that while it has the potential to serve as an informative biomarker, DNA methylation could also be a key to understanding the biology entangled between aging, (de)differentiation, and epigenetic reprogramming. Here we use an unsupervised approach to analyze time associated DNA methylation from both in vivo and in vitro samples to measure an underlying signal that ties these phenomena together. We identify a methylation pattern shared across all three, as well as a signal that tracks aging in tissues but appears refractory to reprogramming, suggesting that aging and reprogramming may not be fully mirrored processes.

Task-based default mode network connectivity predicts cognitive impairment and negative symptoms in first-episode schizophrenia.

Individuals diagnosed with schizophrenia (SZ) demonstrate difficulty distinguishing between internally and externally generated stimuli. These aberrations in "source monitoring" have been theorized as contributing to symptoms of the disorder, including hallucinations and delusions. Altered connectivity within the default mode network (DMN) of the brain has been proposed as a mechanism through which discrimination between self-generated and externally generated events is disrupted. Source monitoring abnormalities in SZ have additionally been linked to impairments in selective attention and inhibitory processing, which are reliably observed via the N100 component of the event-related brain potential elicited during an auditory paired-stimulus paradigm. Given overlapping constructs associated with DMN connectivity and N100 in SZ, the present investigation evaluated relationships between these measures of disorder-related dysfunction and sought to clarify the nature of task-based DMN function in SZ. DMN connectivity and N100 measures were assessed using EEG recorded from SZ during their first episode of illness (N = 52) and demographically matched healthy comparison participants (N = 25). SZ demonstrated less evoked theta-band connectivity within DMN following presentation of pairs of identical auditory stimuli than HC. Greater DMN connectivity among SZ was associated with better performance on measures of sustained attention (p = .03) and working memory (p = .09), as well as lower severity of negative symptoms, though it was not predictive of N100 measures. Together, present findings provide EEG evidence of lower task-based connectivity among first-episode SZ, reflecting disruptions of DMN functions that support cognitive processes. Attentional processes captured by N100 appear to be supported by different neural mechanisms.

Bumble bee responses to climate and landscapes: Investigating habitat associations and species assemblages across geographic regions in the United States of America.

Bumble bees are integral pollinators of native and cultivated plant communities, but species are undergoing significant changes in range and abundance on a global scale. Climate change and land cover alteration are key drivers in pollinator declines; however, limited research has evaluated the cumulative effects of these factors on bumble bee assemblages. This study tests bumble bee assemblage (calculated as richness and abundance) responses to climate and land use by modeling species-specific habitat requirements, and assemblage-level responses across geographic regions. We integrated species richness, abundance, and distribution data for 18 bumble bee species with site-specific bioclimatic, landscape composition, and landscape configuration data to evaluate the effects of multiple environmental stressors on bumble bee assemblages throughout 433 agricultural fields in Florida, Indiana, Kansas, Kentucky, Maryland, South Carolina, Utah, Virginia, and West Virginia from 2018 to 2020. Distinct east versus west groupings emerged when evaluating species-specific habitat associations, prompting a detailed evaluation of bumble bee assemblages by geographic region. Maximum temperature of warmest month and precipitation of driest month had a positive impact on bumble bee assemblages in the Corn Belt/Appalachian/northeast, southeast, and northern plains regions, but a negative impact on the mountain region. Further, forest land cover surrounding agricultural fields was highlighted as supporting more rich and abundant bumble bee assemblages. Overall, climate and land use combine to drive bumble bee assemblages, but how those processes operate is idiosyncratic and spatially contingent across regions. From these findings, we suggested regionally specific management practices to best support rich and abundant bumble bee assemblages in agroecosystems. Results from this study contribute to a better understanding of climate and landscape factors affecting bumble bees and their habitats throughout the United States.