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Antimitochondrial antibody-positive primary biliary cholangitis (AMA-pos PBC) is an autoimmune disorder in which monoclonal antibodies are produced against epitopes in the mitochondrial membranes of biliary epithelial cells, resulting in progressive nonsuppurative biliary cholangitis. Up to 5% of patients lack these autoantibodies, termed antimitochondrial antibody-negative (AMA-neg) PBC. Although a somewhat new variant of AMA-pos PBC, it is not an overlapping syndrome. Few studies to date have described this phenomenon. An 87-year-old woman was referred to our clinic with elevated serum alkaline phosphatase (714 U/L). She reported fatigue but no other symptoms. A physical examination revealed a benign lesion and bilateral lower extremity swelling secondary to lymphedema. The serological profile was significant for a high antinuclear antibody titer (>1:2,560) with a centromere pattern and negative for antimitochondrial antibody (AMA). The hepatitis panel was negative for viruses A, B, and C. Her serum immunoglobulin G level was 871 mg/dL (normal

Background Though compulsive drinking is a hallmark of alcohol use disorder (AUD), little is known of the neural mechanisms driving this behavior. To further the understanding of the neural underpinnings of this compulsivity, a metanalytic approach was used to examine grey matter (GM) volume differences related to AUD, and contrast these differences with GM volume differences in obsessive-compulsive disorder (OCD), to find common underlying regional brain differences. Methods We systematically meta-analyzed case-control studies investigating GM volume that used whole brain voxel-based morphometry separately for AUD and OCD, and then the results of both were directly compared. The Seed-based d Mapping (SDM) software was used to perform the metanalyses. Results The AUD metanalysis used 19 citations, with 736 AUD and 827 control individuals. The OCD metanalysis had 25 citations with 995 OCD and 1177 control individuals. The AUD group showed decreased GM in areas including frontal, limbic, temporal and cerebellar regions. The OCD group had decreased GM in frontal and insular regions but increases in the hypothalamus and brainstem. Importantly, the main outcome showed both groups had decreased GM overlapping in the anterior cingulate and insula. Brain regions were p Conclusions Common brain regional differences in the anterior cingulate and insula that overlap between AUD and OCD suggest that interventions targeting these regions could prove to be beneficial in treating compulsive drinking related to AUD. Further research into the functional role of these brain regions in the etiology of compulsive drinking in AUD is warranted.

Coastal ecosystems play a disproportionately large role in society, and climate change is altering their ecological structure and function, as well as their highly valued goods and services. In the present article, we review the results from decade-scale research on coastal ecosystems shaped by foundation species (e.g., coral reefs, kelp forests, coastal marshes, seagrass meadows, mangrove forests, barrier islands) to show how climate change is altering their ecological attributes and services. We demonstrate the value of site-based, long-term studies for quantifying the resilience of coastal systems to climate forcing, identifying thresholds that cause shifts in ecological state, and investigating the capacity of coastal ecosystems to adapt to climate change and the biological mechanisms that underlie it. We draw extensively from research conducted at coastal ecosystems studied by the US Long Term Ecological Research Network, where long-term, spatially extensive observational data are coupled with shorter-term mechanistic studies to understand the ecological consequences of climate change.

Social attention involves selectively attending to and encoding socially relevant information. We investigated the neural systems underlying the wide range of variability in both social attention ability and social experience in a neurotypical sample. Participants performed a selective social attention task while undergoing fMRI and completed self-report measures of social functioning. Using connectome-based predictive modeling, we demonstrated that individual differences in whole-brain functional connectivity patterns during selective attention to faces predicted task performance. Individuals with more cerebellar-occipital connectivity performed better on the social attention task, suggesting more efficient social information processing. Then, we estimated latent communities of autistic and socially anxious traits using exploratory graph analysis to decompose heterogeneity in social functioning between individuals. Connectivity strength within the identified social attention network was associated with social skills, such that more temporal-parietal connectivity predicted fewer challenges with social communication and interaction. These findings demonstrate that individual differences in functional connectivity strength during a selective social attention task are related to varying levels of self-reported social skill.

Functional connectivity between the amygdala and the medial prefrontal cortex (mPFC) has been identified as a neural substrate of emotion regulation that undergoes changes throughout development, with a mature profile typically emerging at 10 years of age. Maternal bonding in childhood has been shown to buffer amygdala reactivity and to influence the trajectory of amygdala–mPFC coupling. The oxytocinergic system is critical in the development of social behavior and maternal bonding. Early-life parental care influences the methylation status of the oxytocin receptor (OXTRm) in animal models and humans, and higher OXTRm is associated with lower amygdala–PFC functional connectivity in adults. Using a neuroimaging-epigenetic approach, we investigated saliva-derived OXTRm as a biological marker of structural and functional connectivity maturation in 57 typically developing children (P OXTRm are associated with a more adult-like functional connectivity profile. Concurrently, more adult-like functional connectivity was associated with higher reported self-control and more diffusion streamlines between the amygdala and mPFC. OXTRm mediates the association between structural and functional connectivity with higher levels of OXTRm being associated with more streamlines. Lastly, we also find that lower OXTRm blunts the association between amygdala–mPFC connectivity and future internalizing behaviors in early adolescence. These findings implicate OXTRm as a biological marker at the interface of the social environment and amygdala–mPFC connectivity in emotional and behavioral regulation. Ultimately, identification of neurobiological markers may lead to earlier detection of children at risk for socio-emotional dysfunction.

Sea-level rise (SLR) and obstructions to sediment delivery pose challenges to the persistence of estuarine habitats and the ecosystem services they provide. Restoration actions and sediment management strategies may help mitigate such challenges by encouraging the vertical accretion of sediment in and horizontal migration of tidal forests and marshes. We used a process-based soil accretion model (Coastal Wetland Equilibrium Model) combined with a habitat classification model (MOSAICS) to estimate the effects of SLR, suspended sediment, and inland habitat migration on estuarine habitats, soil carbon accumulation, and economic value of climate change mitigation of carbon accumulation (social cost of carbon dioxide) in a macrotidal estuary in the northwest USA over 100 years (2011 to 2110). Under present-day sediment levels, we projected that after 100 years, most high salt marsh would remain with < 100 cm SLR, but substantial area converted to transitional (low) salt marsh and mudflat with ≥ 100 cm SLR. Increasing sediment availability increased the projected resilience of transitional salt marsh to SLR but did not prevent declines in high marsh area. Projected total carbon accumulation plateaued or declined with ≥ 100 cm SLR, yet the economic value of carbon accumulation continued to rise over time, suggesting that the value of this ecosystem service was resilient to SLR. Doubling or tripling sediment availability increased projected carbon accumulation up to 7.69 and 14.2 kg m−2 and increased total economic value up to $373,000 and $710,000, respectively. Allowing marsh migration supported conversion of upland to freshwater marsh, with slight increases in carbon accumulation. These results inform climate adaptation planning for wetland managers seeking to understand the resilience of estuarine habitats and ecosystem services to SLR under multiple management strategies.

HighlightsThree rigorous, methods for estimating influent-effluent mass flow differences due to biogas generation in manure-based anaerobic co-digestion systems are presented.The methods developed reveal that influent-effluent mass flow differences are driven by waste biochemical conversion - biogas water vapor content is insignificant.A simple, input-based method produced comparable results to two, more complex, output-based methods, when tested using 12 months of data collected from three dairy-based anaerobic co-digestion systems.Abstract.During co-digestion of dairy manure and off-farm organic waste in farm anaerobic co-digestion (AcoD) systems, the process’s conversion of biodegradable organics to biogas reduces the volumetric mass (or mass-volume) of the effluent discharged compared to the mass-volume fed. In this study, we present three methods for estimating the mass-flow difference between influent and effluent due to conversion to biogas based on widely accepted, rigorously applied, biological and engineering principles. Monthly operating data from three full-scale AcoD systems, operated under different conditions for a full year were used to compare results using the three calculation methods. Results revealed that the predictions of influent mass flow loss obtained using a simplified input-based method primarily based on influent volumetric flow rates and biodegradability data were in good agreement with those obtained using more accurate, real-time data, namely methane concentration and biogas production. For AcoD systems adding off-site wastes at around 30% or less of the total influent volatile solids (VS), the estimated reduction in effluent flow was in the range of 3% or less. In one case, for VS additions up to approximately 60% of the AcoD system’s influent load, the reduction was 12%. Accepted fundamental water vapor relationships were also applied to biogas generation. Biogas water vapor loses were estimated to comprise approximately 0.2% of the total biogas mass-volume typically produced. Since in most anaerobic digestion systems, biogas condensate water is returned to the influent, this insignificant amount may be ignored. Keywords: Anaerobic, Biogas, Co-digestion, Dairy manure, Digestion, Food waste, Volume-mass flow conversion.

Quantitative, broadly applicable metrics of resilience are needed to effectively manage tidal marshes into the future. Here we quantified three metrics of temporal marsh resilience: time to marsh drowning, time to marsh tipping point, and the probability of a regime shift, defined as the conditional probability of a transition to an alternative super-optimal, suboptimal, or drowned state. We used organic matter content (loss on ignition, LOI) and peat age combined with the Coastal Wetland Equilibrium Model (CWEM) to track wetland development and resilience under different sea-level rise scenarios in the Sacramento-San Joaquin Delta (Delta) of California. A 100-year hindcast of the model showed excellent agreement (R2 = 0.96) between observed (2.86 mm/year) and predicted vertical accretion rates (2.98 mm/year) and correctly predicted a recovery in LOI (R2 = 0.76) after the California Gold Rush. Vertical accretion in the tidal freshwater marshes of the Delta is dominated by organic production. The large elevation range of the vegetation combined with high relative marsh elevation provides Delta marshes with resilience and elevation capital sufficiently great to tolerate centenary sea-level rise (CLSR) as high as 200 cm. The initial relative elevation of a marsh was a strong determinant of marsh survival time and tipping point. For a Delta marsh of average elevation, the tipping point at which vertical accretion no longer keeps up with the rate of sea-level rise is 50 years or more. Simulated, triennial additions of 6 mm of sediment via episodic atmospheric rivers increased the proportion of marshes surviving from 51% to 72% and decreased the proportion drowning from 49% to 28%. Our temporal metrics provide critical time frames for adaptively managing marshes, restoring marshes with the best chance of survival, and seizing opportunities for establishing migration corridors, which are all essential for safeguarding future habitats for sensitive species.

Epigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. In this study, we use GrimAge, an epigenetic clock correlated to several blood plasma proteins, to longitudinally investigate brain cellular microstructure in axonal white matter from a cohort of healthy aging individuals. Given the blood plasma correlations used to develop GrimAge, a specific focus was made on white matter hyperintensities, a visible neurological manifestation of small vessel disease, and the axonal pathways throughout each individual’s brain affected by their unique white matter hyperintensity location and volume. 98 subjects over 55 years of age were scanned at baseline with 41 returning for a follow-up scan 2 years later. Using diffusion MRI lesionometry, we reconstructed subject-specific networks of affected axonal tracts and examined the diffusion cellular microstructure composition of these areas, both at baseline and longitudinally, for evidence of cellular degeneration. A chronological age-adjusted version of GrimAge was significantly correlated with baseline WMH volume and markers of neuronal decline, indicated by increased extracellular free water, increased intracellular signal, and decreased axonal signal within WMH. By isolating subject-specific axonal regions ‘lesioned’ by crossing through a WMH, age-adjusted GrimAge was also able to predict longitudinal development of similar patterns of neuronal decline throughout the brain. This study is the first to establish a relationship between accelerated epigenetic GrimAge and brain cellular microstructure in humans.

Thiols easily react with [1.1.1]propellane to give sulfur-substituted bicyclo[1.1.1]pentanes in radical reactions, but this reactivity is not replicated in the case of heterocyclic thiols. Herein, we address this issue by electrophilically activating [1.1.1]propellane to promote its iodo-sulfenylation with 10 classes of heterocyclic thiols in two protocols that can be conducted on a multigram scale without exclusion of air or moisture.

Hepatocellular carcinoma (HCC) remains an important form of cancer-related morbidity and mortality in the U.S. and worldwide. Previous U.S.-based studies on survival suggest ethnic disparities in HCC patients, but the complex interplay of multiple factors that contribute are still incompletely understood. Here we considered the influences of risk factors contributing towards HCC survival, including ethnic background, over ten years at a premier academic medical center with a majority (57.20%) African American (AA) population. Retrospective HCC data were collected from 2008–2018 at LSUHSC-Shreveport, an urban tertiary medical center. Data included demographics, comorbidities, liver disease characteristics, and tumor parameters. Statistical analysis was performed using Chi Square and one-way ANOVA. Results: 229 HCC patients were identified (male 78.6%). The mean HCC age at diagnosis was 61 years (SD = 7.3). Compared to non-Hispanic Caucasians (42.7%), AA patients (57.2% of total) were older at presentation, had more frequent diabetes/dyslipidemia/NAFLD (45 (34.3%) compared with 19 (19.3%) in non-Hispanic Caucasians, p = 0.02), and had a larger HCC burden at diagnosis. We conclude that compared to white patients, despite having similar BMI and MELD scores and rates of portal vein thrombosis, AA patients with HCC in our cohort were older at presentation, had a significantly increased incidence of modifiable metabolic risk factors including diabetes, higher AFP values, increased incidence of gallstones, and larger sized HCCs, and were more likely to be outside Milan criteria. These findings have important prognostic and diagnostic implications for developing a more targeted HCC surveillance program.

It’s been an extraordinary two years, for everyone, and let’s hope it is never to be repeated.

Infection with pathogenic free-living amoebae, including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because of catastrophic central nervous system involvement. Efficacious treatment options for these infections are lacking, and the mortality rate due to infection is high. Previously, we evaluated the N. fowleri glucokinase (NfGlck) as a potential target for therapeutic intervention, as glucose metabolism is critical for in vitro viability. Here, we extended these studies to the glucokinases from two other pathogenic free-living amoebae, including Acanthamoeba castellanii (AcGlck) and B. mandrillaris (BmGlck). While these enzymes are similar (49.3% identical at the amino acid level), they have distinct kinetic properties that distinguish them from each other. For ATP, AcGlck and BmGlck have apparent K(m) values of 472.5 and 41.0 μM, while Homo sapiens Glck (HsGlck) has a value of 310 μM. Both parasite enzymes also have a higher apparent affinity for glucose than the human counterpart, with apparent K(m) values of 45.9 μM (AcGlck) and 124 μM (BmGlck) compared to ~8 mM for HsGlck. Additionally, AcGlck and BmGlck differ from each other and other Glcks in their sensitivity to small molecule inhibitors, suggesting that inhibitors with pan-amoebic activity could be challenging to generate.

Perceived discrimination has been associated with a higher prevalence of e-cigarette use among adult samples. However, little is understood about the relationship between discrimination and various vaping behaviors among college students.

Background People with chronic kidney disease (CKD) are at high risk of polypharmacy. However, no previous study has investigated international prescribing patterns in this group. This article aims to examine prescribing and polypharmacy patterns among older people with advanced CKD across the countries involved in the European Quality (EQUAL) study. Methods The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced CKD. Baseline demographic, clinical and medication data were analysed and reported descriptively. Polypharmacy was defined as ≥5 medications and hyperpolypharmacy as ≥10. Univariable and multivariable linear regressions were used to determine associations between country and the number of prescribed medications. Univariable and multivariable logistic regression were used to determine associations between country and hyperpolypharmacy. Results Of the 1317 participants from five European countries, 91% were experiencing polypharmacy and 43% were experiencing hyperpolypharmacy. Cardiovascular medications were the most prescribed medications (mean 3.5 per person). There were international differences in prescribing, with significantly greater hyperpolypharmacy in Germany {odds ratio (OR) 2.75 [95% confidence interval (CI) 1.73–4.37]; P Conclusions Hyperpolypharmacy is common among older people with advanced CKD, with significant international differences in the number of medications prescribed. Practice variation may represent a lack of consensus regarding appropriate prescribing for this high-risk group for whom pharmacological treatment has great potential for harm as well as benefit.

Healthcare expenditure is on the rise placing greater emphasis on operational excellence, cost containment, and high quality of care. Significant variation is seen in operating room (OR) costs with common surgical procedures such as laparoscopic appendectomy. Surgeons can influence cost through the selection of instrumentation for common surgical procedures such as laparoscopic appendectomy. We aimed to quantify the cost of laparoscopic appendectomy in our healthcare system and compare cost variations to operative times and outcomes. We performed a retrospective review of laparoscopic appendectomies in a large regional healthcare system during one-year period (2018). Operating room supply costs and procedure durations were obtained for each hospital. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) outcomes and demographics were compared to the costs for each hospital. A total of 4757 laparoscopic appendectomies were performed at 20 hospitals (27 to 522 per hospital) by 233 surgeons. The average supply cost per case ranged from $650 to $1067. Individual surgeon cost ranged from $197 to $1181. The average operative time was 41 min (range 33 to 60 min). There was no association between lower cost and longer operative time. The patient demographics and comorbidities were similar between sites. There were no significant differences in postoperative complications between high- and low-cost centers. The items with the greatest increase in cost were single-use energy devices (SUD) and endoscopic stapler. We estimate that a saving of over $417 per case is possible by avoiding the use of energy devices and may be as high as $ 984 by adding selective use of staplers. These modifications would result in an annual savings of $1 million for our health system and more than $ 125 million nationwide. Performing laparoscopic appendectomy with reusable instruments and finding alternatives to expensive energy devices and staplers can significantly decrease costs and does not increase operative time or postoperative complications.

In this study, we examine the rhizosphere processes influencing organic P (Po) utilization in soil with low inorganic P (Pi) availability and how they change with plant development. Interactions between plants and the rhizosphere microbial community triggered by P deficiency may provide insights into the role of P availability on degradation of soil organic matter (SOM). Maize (Zea mays) plants were grown in low P containing soil. Soil pH, potential acid phosphatase activities, soil C and P pools, microbial biomass C and P, microbial community structure, and plant P content were analyzed at different vegetative growth stages (VGS). At early VGS, the plants were P deficient which correlated with greater rhizosphere potential acid phosphatase activity, degradation of SOM and a reduction in the Po pool. At late VGS, the plants appeared to recover which correlated with a decrease in Meh (III) extractable P, an increase in microbial biomass C and P, change in microbial community structure, and greater total P (TP) in the plant biomass. The mineralization of organic C and Po are coupled in low P soil where N is not limited. The overall findings from this study advance our understanding of the coupled biogeochemical rhizosphere processes controlling P cycling at different plant growth stages and notably the importance of Po to the overall P needs of plants in soil with low Pi availability.

The peroxidation of unsaturated fatty acids is a widely recognized metabolic process that creates a complex mixture of volatile organic compounds including aldehydes. Elevated levels of reactive oxygen species in cancer cells promote random lipid peroxidation, which leads to a variety of aldehydes. In the case of lung cancer, many of these volatile aldehydes are exhaled and are of interest as potential markers of the disease. Relevant studies reporting aldehydes in the exhaled breath of lung cancer patients were collected for this review by searching the PubMed and SciFindern databases until 25 May 2022. Information on breath test results, including the biomarker collection, preconcentration, and quantification methods, was extracted and tabulated. Overall, 44 studies were included spanning a period of 34 years. The data show that, as a class, aldehydes are significantly elevated in the breath of lung cancer patients at all stages of the disease relative to healthy control subjects. The type of aldehyde detected and/or deemed to be a biomarker is highly dependent on the method of exhaled breath sampling and analysis. Unsaturated aldehydes, detected primarily when derivatized during preconcentration, are underrepresented as biomarkers given that they are also likely products of lipid peroxidation. Pentanal, hexanal, and heptanal were the most reported aldehydes in studies of exhaled breath from lung cancer patients.