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Abstract Biological soil crusts (BSC) are important contributors to nutrient cycling in arid environments such as the Sonoran Desert. BSC at an urban (University Indian Ruins) and at a non-urban site (Santa Rita Experimental Range) were compared to determine if their structure or function was influenced by proximity to an urban environment. The Step Point method was used in the field to determine ground cover; which was found to be similar between sites. However, the spatial distribution of the BSCs was significantly different, such that more BSCs were found under plants at the non-urban site (P

The purpose of this work was to investigate the presence of C. zemplinina yeasts in Sicilian musts and grapes and to identify strains of oenological interest. We report on the taxonomical reclassification of Candida yeast isolates from Sicilian musts and on the selection of one strain of oenological interest (Cz3), based on mixed micro-fermentation experiments in sterile Nero d'Avola musts. Our results show that Candida zemplinina is abundant in Sicilian grapes and musts, and that the Cz3 strain is suitable for Candida zemplinina/Saccharomyces cerevisiae mixed fermentations. The higher glycerol content and the lower ethanol level stood out as the most promising features of the wines obtained upon sequential inoculation of the Cz3 and (S. cerevisiae) NDA21 yeast starters. We therefore have isolated a Sicilian Cz strain endowed with very promising features for the future development of mixed fermentation protocols. [ABSTRACT FROM AUTHOR]

As sessile organisms, plants must be able to complete their life cycle in place and therefore tolerance to abiotic stress has had a major role in shaping biogeographical patterns. However, much of what we know about plant tolerance to abiotic stresses is based on studies of just a few plant species, most notably the model species Arabidopsis thaliana. In this study we examine natural variation in the stress responses of five diverse Boechera (Brassicaceae) species. Boechera plants were exposed to basal and acquired combined heat and high light stress. Plant response to these stresses was evaluated based on chlorophyll fluorescence measurements, induction of leaf chlorosis, and gene expression. Many of the Boechera species were more tolerant to heat and high light stress than A. thaliana. Gene expression data indicates that two important marker genes for stress responses: APX2 (Ascorbate peroxidase 2) and HsfA2 (Heat shock transcription factor A2) have distinct species-specific expression patterns. The findings of species-specific responses and tolerance to stress indicate that stress pathways are evolutionarily labile even among closely related species.

We developed a new protocol for winery mixed fermentations, using the selected Candida zemplinina yeast strain Cz3. The results of a two-year study, in which red musts (Merlot in 2010; Merlot, Nero d'Avola and Frappato in 2011) were inoculated with Cz3, is discussed. These wines were compared with wines obtained by inoculation with commercial Saccharomyces cerevisiae yeast strains (NDA21 and AR06 in 2010; NDA21 in 2011), or with those obtained by spontaneous fermentation (only in 2011). The inoculation of Cz3 always resulted in a two-phase fermentation: the first phase was driven by the C. zemplinina strain, while the second was dominated by the indigenous S. cerevisiae yeasts coming from the grapes and/or the winery. In both years the Cz3 wines contained less alcohol and more glycerol than those made with the commercial yeast strains or those obtained by spontaneous fermentation. Triangle tests showed that a sensorial difference between wines could only be achieved through the utilisation of Cz3. [ABSTRACT FROM AUTHOR]

Introduction: ASCEND PLUS is a randomised controlled trial assessing the effects of oral semaglutide on the primary prevention of cardiovascular events in around 20,000 individuals with type 2 diabetes in the UK. The trial's innovative design includes a decentralised direct-to-participant invitation, recruitment, and follow-up model, relying on self-completion of online forms or telephone or video calls with research nurses, with no physical sites. Extensive patient and public involvement and engagement (PPIE) was essential to the design and conduct of ASCEND PLUS., Aim: To report the process and conduct of PPIE activity in ASCEND PLUS, evaluate effects on trial design, reflect critically on successes and aspects that could have been improved, and identify themes and learning relevant to implementation of PPIE in future trials., Methods: PPIE activity was coordinated centrally and included six PPIE focus groups and creation of an ASCEND PLUS public advisory group (PAG) during the design phase. Recruitment to these groups was carefully considered to ensure diversity and inclusion, largely consisting of adults living with type 2 diabetes from across the UK. Two members of the PAG also joined the trial Steering Committee. Steering Committee meetings, focus groups, and PAG meetings were conducted online, with two hybrid workshops to discuss PPIE activity and aspects of the trial., Results: PPIE activity was critical to shaping the design and conduct of ASCEND PLUS. Key examples included supporting choice for participants to either complete the screening/consent process independently online, or during a telephone or video call interview with a research nurse. A concise 'initial information leaflet' was developed to be sent with the initial invitations, with the 'full' information leaflet sent later to those interested in joining the trial. The PAG reviewed the content and format of participant- and public-facing materials, including written documents, online screening forms, animated videos, and the trial website, to aid clarity and accessibility, and provided input into the choice of instruments to assess quality of life., Conclusions: PPIE is integral in ASCEND PLUS and will continue throughout the trial. This involvement has been critical to optimising the trial design, successfully obtaining regulatory and ethical approval, and conducting the trial., (© 2024. The Author(s).)

Human ageing is a normal process and does not necessarily result in the development of frailty. A mix of genetic, environmental, dietary, and lifestyle factors can have an impact on ageing, and whether an individual develops frailty. Frailty is defined as the loss of physiological reserve both at the physical and cellular levels, where systemic processes such as oxidative stress and inflammation contribute to physical decline. The newest "omics" technology and systems biology discipline, metabolomics, enables thorough characterisation of small-molecule metabolites in biological systems at a particular time and condition. In a biological system, metabolites-cellular intermediate products of metabolic reactions-reflect the system's final response to genomic, transcriptomic, proteomic, epigenetic, or environmental alterations. As a relatively newer technique to characterise metabolites and biomarkers in ageing and illness, metabolomics has gained popularity and has a wide range of applications. We will give a comprehensive summary of what is currently known about metabolomics in studies of ageing, with a focus on biomarkers for frailty. Metabolites related to amino acids, lipids, carbohydrates, and redox metabolism may function as biomarkers of ageing and/or frailty development, based on data obtained from human studies. However, there is a complexity that underpins biological ageing, due to both genetic and environmental factors that play a role in orchestrating the ageing process. Therefore, there is a critical need to identify pathways that contribute to functional decline in people with frailty., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Abdullah, Akpan, Phelan and Wright.)

Objective: We aimed to determine the association of COVID-19 vaccination with flares of systemic rheumatic disease (SRD)., Methods: Adults with systemic rheumatic disease (SRD) in a single-center COVID-19 Rheumatology Registry were invited to enroll in a study of flares. COVID-19 vaccine information from March 5, 2021, to September 6, 2022, was obtained from chart review and self-report. Participants self-reported periods of SRD flare and periods without SRD flare. "Hazard periods" were defined as the time before a self-report of flare and "control periods" as the time before a self-report of no flare. The association between flare and COVID-19 vaccination was evaluated during hazard and control periods through univariate conditional logistic regression stratified by participant, using lookback windows of 2, 7, and 14 days., Results: A total of 434 participants (mean ± SD age 59 ± 13 years, 84.1% female, 81.8% White, 64.5% with inflammatory arthritis, and 27.0% with connective tissue diseases) contributed to both the hazard and control periods and were included in analysis. A total of 1,316 COVID-19 vaccinations were identified (58.5% Pfizer-BioNTech, 39.5% Moderna, and 1.4% Johnson & Johnson); 96.1% of participants received at least one dose and 93.1% at least two doses. There was no association between COVID-19 vaccination and flares in the subsequent 2, 7, or 14 days (odds ratio [OR] 1.46, 95% confidence interval [CI] 0.86-2.46; OR 1.09, 95% CI 0.76-1.55; and OR 0.85, 95% CI 0.64-1.13, respectively). Analyses stratified on sex, age, SRD subtype, and vaccine manufacturer similarly showed no association between vaccination and flare., Conclusion: COVID-19 vaccination was not associated with flares in this cohort of participants with SRD. These data are reassuring and can inform shared decision-making on COVID-19 immunization., (© 2024 American College of Rheumatology.)

The number of young adults seeking help for emotional distress, subsyndromal-syndromal mood/anxiety symptoms, including those associated with neuroticism, is rising and can be an early manifestation of mood/anxiety disorders. Identification of gray matter (GM) thickness alterations and their relationship with neuroticism and mood/anxiety symptoms can aid in earlier diagnosis and prevention of risk for future mood and anxiety disorders. In a transdiagnostic sample of young adults (n = 252;177 females; age 21.7 ± 2), Hypothesis (H) 1:regularized regression followed by multiple regression examined relationships among GM cortical thickness and clinician-rated depression, anxiety, and mania/hypomania; H2:the neuroticism factor and its subfactors as measured by NEO Personality Inventory (NEO-PI-R) were tested as mediators. Analyses revealed positive relationships between left parsopercularis thickness and depression (B = 4.87, p = 0.002), anxiety (B = 4.68, p = 0.002), mania/hypomania (B = 6.08, p ≤ 0.001); negative relationships between left inferior temporal gyrus (ITG) thickness and depression (B = - 5.64, p ≤ 0.001), anxiety (B = - 6.77, p ≤ 0.001), mania/hypomania (B = - 6.47, p ≤ 0.001); and positive relationships between left isthmus cingulate thickness (B = 2.84, p = 0.011), and anxiety. NEO anger/hostility mediated the relationship between left ITG thickness and mania/hypomania; NEO vulnerability mediated the relationship between left ITG thickness and depression. Examining the interrelationships among cortical thickness, neuroticism and mood and anxiety symptoms enriches the potential for identifying markers conferring risk for mood and anxiety disorders and can provide targets for personalized intervention strategies for these disorders., (© 2024. The Author(s).)

Objective: To test the reliability of Medicare claims in measuring vertical integration. We assess the accuracy of a commonly used measure of integration, primary care physician (PCP) practices billing Medicare as a hospital outpatient department (HOPD) in claims., Data Sources and Study Setting: Medicare fee-for-service claims, IQVIA, and CPC+ practice surveys for this study., Study Design: We compare measures of integration from Medicare claims to self-reported indicators of integration from IQVIA and a survey of CPC+ participating practice sites., Data Collection/extraction Methods: We measure integration by using site-of-service billing in the 100% sample of Medicare Carrier claims from 2017-2020. In the IQVIA SK&A (2017-2018), OneKey (2019-2020), and practice survey data (2017-2019), we use self-reported responses to measure integration., Principal Findings: We find that currently most PCP practices sites that report themselves as being integrated with a health system do not bill as an HOPD. In 2017, 11% of CPC+ practices were identified as being vertically integrated in claims, while the equivalent numbers in SK&A and surveys were 52% and 54% integration, respectively. A t-test found that both datasets significantly differed from claims (Survey: 41.3%-45.1%; SK&A: 45.3%-51.1%); this gap persists in 2018-2019., Conclusion: Measuring physician-hospital vertical integration accurately is integral to determining consolidation. The overwhelming majority of PCP practice sites not billing as an HOPD may reflect Medicare regulatory changes that have reduced the financial incentives for doing so. These findings have implications for researchers that study the growth in PCP-hospital integration in health care markets., (© 2024 Health Research and Educational Trust.)

Inherited defects in cytochrome c oxidase (COX) are associated with a substantial subset of diseases adversely affecting the structure and function of the mitochondrial respiratory chain. This multi-subunit enzyme consists of 14 subunits and numerous cofactors, and it requires the function of some 30 proteins to assemble. COX assembly was first shown to be the primary defect in the majority of COX deficiencies 36 years ago. Over the last three decades, most COX assembly genes have been identified in the yeast Saccharomyces cerevisiae , and studies in yeast have proven instrumental in testing the impact of mutations identified in patients with a specific COX deficiency. The advent of accessible genome-wide sequencing capabilities has led to more patient mutations being identified, with the subsequent identification of several new COX assembly factors. However, the lack of genotype-phenotype correlations and the large number of genes involved in generating a functional COX mean that functional studies must be undertaken to assign a genetic variant as being causal. In this review, we provide a brief overview of the use of yeast as a model system and briefly compare the COX assembly process in yeast and humans. We focus primarily on the studies in yeast that have allowed us to both identify new COX assembly factors and to demonstrate the pathogenicity of a subset of the mutations that have been identified in patients with inherited defects in COX. We conclude with an overview of the areas in which studies in yeast are likely to continue to contribute to progress in understanding disease arising from inherited COX deficiencies.

Objectives: To understand the role of health information technology (IT) vendors and health IT functionality in supporting advanced primary care., Study Design: We synthesized multiple rounds of surveys and interviews (2017-2022) from a mixed-methods evaluation of Comprehensive Primary Care Plus (CPC+), a multipayer model developed by CMS. CPC+ was the first federal advanced primary care reform effort that formalized health IT vendors' roles in supporting health IT implementation and specified detailed health IT requirements for practices., Methods: We conducted content analysis to identify cross-cutting themes related to health IT for both practices and vendors, comparing similarities and differences across participants and (when possible) over time., Results: Vendors and practices reported advances in registries and dashboards for improved information management within the practice as well as strengthened relationships between vendors and practices that supported health IT implementation. However, CPC+ practices noted several gaps or challenges using existing functionalities, and both vendors and practices reported broader challenges for more transformative health IT change, particularly the lack of interoperable health information exchange needed to support care management and care coordination. Key factors constraining vendors' investment in further advances included long product development schedules, making it difficult to respond to rapidly evolving model requirements. Vendors also shared that CPC+ practices represented a small fraction of their client base, so investing in developing new functionality was not strategic unless it was more broadly relevant outside CPC+., Conclusions: Continued collaboration among health IT vendors, practices, policy makers, and payers could support continued technological improvements, particularly related to information exchange and communication. Aligning requirements more closely with other federal and private models could also help mitigate the risk for vendors.

Background: Diffuse intrinsic pontine glioma (DIPG) is the most common and deadliest pediatric brainstem tumor and is difficult to treat with chemotherapy in part due to the blood-brain barrier (BBB). Focused ultrasound (FUS) and microbubbles (MBs) have been shown to cause BBB opening, allowing larger chemotherapeutics to enter the parenchyma. Panobinostat is an example of a promising in vitro agent in DIPG with poor clinical efficacy due to low BBB penetrance. In this study, we hypothesized that using FUS to disrupt the BBB allows higher concentrations of panobinostat to accumulate in the tumor, providing a therapeutic effect., Methods: Mice were orthotopically injected with a patient-derived diffuse midline glioma (DMG) cell line, BT245. MRI was used to guide FUS/MB (1.5 MHz, 0.615 MPa peak negative pressure, 1 Hz pulse repetition frequency, 10-ms pulse length, 3 min treatment time)/(25 µL/kg, i.v.) targeting to the tumor location., Results: In animals receiving panobinostat (10 mg/kg, i.p.) in combination with FUS/MB, a 3-fold increase in tumor panobinostat concentration was observed, without significant increase of the drug in the forebrain. In mice receiving 3 weekly treatments, the combination of panobinostat and FUS/MB led to a 71% reduction of tumor volumes ( P = .01). Furthermore, we showed the first survival benefit from FUS/MB improved delivery increasing the mean survival from 21 to 31 days ( P < .0001)., Conclusions: Our study demonstrates that FUS-mediated BBB disruption can increase the delivery of panobinostat to an orthotopic DMG tumor, providing a strong therapeutic effect and increased survival., Competing Interests: The authors declare that they have no competing interests., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Yellowhorn tea (YT) is traditionally used as a lipid-lowering beverage in Mongolian minorities. However, the pharmacological effects of YT extract and its specific metabolic changes in hyperlipidemia models are not fully understood. The aim of this study was to identify biomarkers using untargeted metabolomics techniques and to investigate the mechanisms underlying the changes in metabolic pathways associated with lipid lowering, anti-inflammation and anti-oxidant in hyperlipidemic mice. A high-fat diet (HFD)-induced hyperlipidemic mouse model was established. YT extract was administered as oral gavage at 0.15, 0.3, and 0.6 g/kg doses for 10 weeks. HFD-induced hyperlipidemia and the therapeutic effect of YT extract were evaluated based on histopathology and by assessing blood lipid levels. Liver inflammatory factors and oxidative stress indices were determined using enzyme-linked immunosorbent assays. Liver metabolites were evaluated using untargeted metabolomics. Biochemical and histological examinations showed that YT extract significantly reduced body-weight gain ( p < 0.01) and fat deposition in tissues. YT extract significantly reduced the levels of serum and liver triglyceride and total cholesterol; inflammatory factors [interleukin (IL)-6, IL-1β, and tumor necrosis factor-α]; malondialdehyde; and leptin ( p < 0.05) in hyperlipidemic mice. YT extract also significantly increased the levels of oxidative stress indicators (superoxide dismutase, catalase, and glutathione peroxidase) and adiponectin. Metabolomics studies revealed several endogenous molecules were altered by the high-fat diet and recovery following intervention with YT extract. The metabolites that were significantly different in the liver after YT intake included citicoline, acetylcholine, pyridoxine, and NAD. Pathway analysis indicated that YT extract ameliorated HFD-induced hyperlipidemia in mice via three major metabolic pathways, namely, glycerophospholipid metabolism, vitamin B6 metabolism, and nicotinate and nicotinamide metabolism. This study demonstrates YT extract has profound effects on the alleviation of HFD-induced hyperlipidemia, inflammation and oxidative stress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ta, A., E., Qi, Mu, Feng, Ba, Li, Zhang, Bai and Fu.)

Notwithstanding mass vaccination against specific SARS-CoV-2 variants, there is still a demand for complementary nutritional intervention strategies to fight COVID-19. The bovine milk protein lactoferrin (LF) has attracted interest of nutraceutical, food and dairy industries for its numerous properties-ranging from anti-viral and anti-microbial to immunological-making it a potential functional ingredient in a wide variety of food applications to maintain health. Importantly, bovine LF was found to exert anti-viral activities against several types of viruses, including certain SARS-CoV-2 variants. LF's potential effect on COVID-19 patients has seen a rapid increase of in vitro and in vivo studies published, resulting in a model on how LF might play a role during different phases of SARS-CoV-2 infection. Aim of this narrative review is two-fold: (1) to highlight the most relevant findings concerning LF's anti-viral, anti-microbial, iron-binding, immunomodulatory, microbiota-modulatory and intestinal barrier properties that support health of the two most affected organs in COVID-19 patients (lungs and gut), and (2) to explore the possible underlying mechanisms governing its mode of action. Thanks to its potential effects on health, bovine LF can be considered a good candidate for nutritional interventions counteracting SARS-CoV-2 infection and related COVID-19 pathogenesis.

Understanding neurobiological characteristics of cognitive dysfunction in distinct psychiatric disorders remains challenging. In this secondary data analysis, we examined neurobiological differences in brain response during working memory updating among individuals with bipolar disorder (BD), those with unipolar depression (UD), and healthy controls (HC). Individuals between 18-45 years of age with BD (n = 100), UD (n = 109), and HC (n = 172) were scanned using fMRI while performing 0-back (easy) and 2-back (difficult) tasks with letters as the stimuli and happy, fearful, or neutral faces as distractors. The 2(n-back) × 3(groups) × 3(distractors) ANCOVA examined reaction time (RT), accuracy, and brain activation during the task. HC showed more accurate and faster responses than individuals with BD and UD. Difficulty-related activation in the prefrontal, posterior parietal, paracingulate cortices, striatal, lateral occipital, precuneus, and thalamic regions differed among groups. Individuals with BD showed significantly lower difficulty-related activation differences in the left lateral occipital and the right paracingulate cortices than those with UD. In individuals with BD, greater difficulty-related worsening in accuracy was associated with smaller activity changes in the right precuneus, while greater difficulty-related slowing in RT was associated with smaller activity changes in the prefrontal, frontal opercular, paracingulate, posterior parietal, and lateral occipital cortices. Measures of current depression and mania did not correlate with the difficulty-related brain activation differences in either group. Our findings suggest that the alterations in the working memory circuitry may be a trait characteristic of reduced working memory capacity in mood disorders. Aberrant patterns of activation in the left lateral occipital and paracingulate cortices may be specific to BD., (© 2022. The Author(s).)

Objective: Corydalis bungeana (CB) is a well-used medicinal herb in Mongolian folk medicine and has been traditionally applied as an antiobesity agent. However, the evidence-based pharmacological effects of CB and its specific metabolic alterations in the obese model are not entirely understood. This study aimed to utilize untargeted metabolomic techniques to identify biomarkers and gain mechanistic insight into the serum metabolite alterations associated with weight loss and lipid metabolism in obese rats., Methods: A high-fat high-sugar (HFHS) diet was used to induce obese models in rats. CB extract was orally gavaged at 0.18, 0.9 and 1.8 g/kg doses for six weeks, and feed intake, body weight, fat pad weight, and blood indexes were measured. Blood serum metabolites were evaluated by gas chromatography/quadrupole time-of-flight tandem mass spectrometry (GC-TOF/MS)., Results: The results showed that compared with the obese group, the administration of CB extract caused significant decreases in body weight ( P  < 0.05), feed intake, Lee's index, and perirenal, mesenteric, epididymal fat weight. CB extract also reduced blood triglyceride and total cholesterol levels ( P  < 0.05) of obese rats. Metabolomic findings showed that nine differential metabolites, including pyruvic acid, D -glucuronic acid, malic acid, dimethylglycine, oxoglutaric acid, pantothenic acid, sorbitol acid, fumaric acid and glucose 6-phosphate were identified under CB treatment and altered metabolic pathways such as TCA cycle, pantothenate and CoA biosynthesis, and glycolysis/gluconeogenesis., Conclusion: This study demonstrated weight loss and lipid lowering effects of CB on HFHS diet-induced obese rats and identified nine metabolites as potential biomarkers for evaluating the favorable therapeutic mechanism of CB via regulation of lipid and glucose metabolism., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Diffusion Magnetic Resonance Imaging (dMRI) studies have reported abnormalities in emotion regulation circuits in BD; however, no study has examined the contribution of previous illness on these mechanisms. Using global probabilistic tractography, we aimed to identify neural correlates of previous BD illness and the extent to which these can help predict one-year recurrence of depressive episodes. dMRI data were collected in 70 adults with early-onset BD who were clinically followed for up to 18 years and 39 healthy controls. Higher number of depressive episodes during childhood/adolescence and higher percentage of time with syndromic depression during longitudinal follow-up was associated with lower fractional anisotropy (FA) in focal regions of the forceps minor (left, F = 4.4, p = 0.003; right, F = 3.1, p = 0.021) and anterior cingulum bundle (left, F = 4.7, p = 0.002; right, F = 7.0, p < 0.001). Lower FA in these regions was also associated with higher depressive and anxiety symptoms at scan. Remarkably, those having higher FA in the right cluster of the forceps minor (AOR = 0.43, p = 0.017) and in a cluster of the posterior cingulum bundle (right, AOR = 0.50, p = 0.032) were protected against the recurrence of depressive episodes. Previous depressive symptomatology may cause neurodegenerative effects in the forceps minor that are associated with worsening of BD symptomatology in subsequent years. Abnormalities in the posterior cingulum may also play a role.

Ixeris chinensis (Thunb.) Nakai (IC) is a folk medicinal herb used in Mongolian medical clinics for the treatment of hepatitis and fatty liver diseases even though its pharmacological mechanism has not been well characterized. This study investigated the hepatoprotective mechanism of IC on mice with nonalcoholic fatty liver disease (NAFLD) by integrating gut microbiota and metabolomic analysis. A high-fat diet (HFD) was used to develop nonalcoholic fatty liver disease, after which the mice were treated with oral IC (0.5, 1.5 and 3.0 g/kg) for 10 weeks. HFD induced NAFLD and the therapeutic effects were characterized by pathological and histological evaluations, and the serum indicators were analyzed by ELISA. The gut microbial and metabolite profiles were studied by 16S rRNA sequencing and untargeted metabolomic analysis, respectively. The results showed that the administration of IC resulted in significant decreases in body weight; liver index; serum biomarkers such as ALT, TG, and LDL-C; and the liver inflammatory factors IL-1β, IL-6, and TNF-α. The 16S rRNA sequencing results showed that administration of IC extract altered both the composition and abundance of the gut microbiota. Untargeted metabolomic analysis of liver samples detected a total of 212 metabolites, of which 128 were differentially expressed between the HFD and IC group. IC was found to significantly alter the levels of metabolites such as L-glutamic acid, pyridoxal, ornithine, L-aspartic acid, D-proline, and N4-acetylaminobutanal, which are involved in the regulation of glutamine and glutamate, Vitamin B6 metabolism, and arginine and proline metabolic pathways. Correlation analysis indicated that the effects of the IC extract on metabolites were associated with alterations in the abundance of Akkermansiaceae, Lachnospiraceae, and Muribaculaceae. Our study revealed that IC has a potential hepatoprotective effect in NAFLD and that its function might be linked to improvements in the composition of gut microbiota and their metabolites.

Soil lead (Pb) contamination is a recognized environmental and global health problem. Phytoextraction of Pb using switchgrass ( Panicum virgatum L.), a second-generation biofuel crop, is typically enhanced by soil chelation. The effectiveness of four different chelating agents, phytic acid (inositol hexaphosphate), citric acid, NTA (nitrilotriacetic acid), and EDTA (ethylenediaminetetraacetic acid) was examined in pot culture. Plants treated with EDTA (1 mM) showed significantly higher shoot Pb concentrations compared to control plants and plants treated with other chelates. Lead-solubility following phytoextraction was examined by soil washing using 0.01 and 0.05 M acetic acid as an extractant solution revealed no significant differences in Pb concentrations in soil among different chelate treatments and control. Furthermore, the effects of different concentrations (1, 2, 5 and 10 mM) of NTA on Pb phytoextraction of switchgrass were examined. Plants receiving 5 mM and 10 mM NTA had significantly higher foliage concentrations of Pb compared to plants treated with lower levels (1 and 2 mM) of NTA. Moreover, the effect of NTA application alone was significantly improved by a combined application of Triton X-100, an alkyl polyglucoside (APG); the Pb concentration in the foliage of switchgrass was more than doubled when treated with NTA combined with APG. The use of NTA combined with APG has great potential in improving phytoextraction efficiencies of switchgrass on Pb-contaminated soils.

Biological soil crusts (BSC) are important contributors to nutrient cycling in arid environments such as the Sonoran Desert. BSC at an urban (University Indian Ruins) and at a non-urban site (Santa Rita Experimental Range) were compared to determine if their structure or function was influenced by proximity to an urban environment. The Step Point method was used in the field to determine ground cover; which was found to be similar between sites. However, the spatial distribution of the BSCs was significantly different, such that more BSCs were found under plants at the non-urban site (P < 0.05). Relative gross photosynthesis was measured in the lab by addition of a watering event. Gross photosynthesis was found to be higher in the non-urban BSCs (P < 0.001), indicating lowered productivity in urban BSCs due to effects caused by proximity to urban environments. This study provides evidence that BSCs at urbanized sites are affected functionally, and therefore may be contributing differently to carbon and nitrogen cycling in these ecosystems., (© 2022. The Author(s).)

Bipolar disorder (BD) is highly heritable. Identifying objective biomarkers reflecting pathophysiological processes predisposing to, versus protecting against BD, can help identify BD risk in offspring of BD parents. We recruited 21 BD participants with a first-degree relative with BD, 25 offspring of BD parents, 27 offspring of comparison parents with non-BD psychiatric disorders, and 32 healthy offspring of healthy parents. In at-risk groups, 23 had non-BD diagnoses and 29, no Axis-I diagnoses(healthy). Five at-risk offspring who developed BD post scan(Converters) were included. Diffusion imaging(dMRI) analysis with tract segmentation identified between-group differences in the microstructure of prefrontal tracts supporting emotional regulation relevant to BD: forceps minor, anterior thalamic radiation(ATR), cingulum bundle(CB), and uncinate fasciculus(UF). BD participants showed lower fractional anisotropy (FA) in the right CB (anterior portion) than other groups (q < 0.05); and in bilateral ATR (posterior portion) versus at-risk groups (q < 0.001). Healthy, but not non-BD, at-risk participants showed significantly higher FA in bilateral ATR clusters than healthy controls (qs < 0.05). At-risk groups showed higher FA in these clusters than BD participants (qs < 0.05). Non-BD versus healthy at-risk participants, and Converters versus offspring of BD parents, showed lower FA in the right ATR cluster (qs < 0.05). Low anterior right CB FA in BD participants versus other groups might result from having BD. High bilateral ATR FA in at-risk groups, and in healthy at-risk participants, versus healthy controls might protect against BD/other psychiatric disorders. Absence of elevated right ATR FA in non-BD versus healthy at-risk participants, and in Converters versus non-converter offspring of BD parents, might lower protection against BD in at-risk groups., (© 2021. The Author(s).)

In October 2019, public health surveillance systems in Scotland identified an increase in the number of reported infections of Shiga toxin-producing Escherichia coli (STEC) O26:H11 involving bloody diarrhoea. Ultimately, across the United Kingdom (UK) 32 cases of STEC O26:H11 stx1a were identified, with the median age of 27 years and 64% were male; six cases were hospitalised. Among food exposures there was an association with consuming pre-packed sandwiches purchased at outlets belonging to a national food chain franchise (food outlet A) [odds ratio (OR) = 183.89, P < 0.001]. The common ingredient identified as a component of the majority of the sandwiches sold at food outlet A was a mixed salad of Apollo and Iceberg lettuce and spinach leaves. Microbiological testing of food and environmental samples were negative for STEC O26:H11, although STEC O36:H19 was isolated from a mixed salad sample taken from premises owned by food outlet A. Contamination of fresh produce is often due to a transient event and detection of the aetiological agent in food that has a short-shelf life is challenging. Robust, statistically significant epidemiological analysis should be sufficient evidence to direct timely and targeted on-farm investigations. A shift in focus from testing the microbiological quality of the produce to investigating the processes and practices through the supply chain and sampling the farm environment is recommended.

Background/aim: We evaluated timeliness of care at a safety-net hospital after implementation of a multidisciplinary breast program., Patients and Methods: A prospective database of patients with breast cancer was created after multidisciplinary breast program initiation in 2018. Patients were tracked to obtain time to completion of diagnostic imaging, biopsy, and treatment initiation. Patients with breast cancer diagnosed from 2015-2017 were reviewed for comparison., Results: A total of 102 patients were identified. There was no statistical difference in time to completion of imaging, biopsy, and initial treatment between the 2018 and the 2015-2017 cohorts (p>0.05). No statistical difference was observed in time to completion of imaging, biopsy, and initial treatment between different races (p>0.05)., Conclusion: Within the same socioeconomic status, there was no differential delivery of screening, work-up, and treatment by race. Despite protocol implementations, efficiency of care remained limited in a safety-net hospital with lack of financial resources., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Approximately one in three of all older adults fall each year, with wide ranging physical, psychosocial and healthcare-related consequences. Exercise-based interventions are the cornerstone for falls prevention programmes, yet these are not consistently provided, do not routinely address all components of the balance system and are often not well attended. The HOLOBalance system provides an evidence-based balance training programme delivered to patients in their home environment using a novel technological approach including an augmented reality virtual physiotherapist, exergames and a remote monitoring system. The aims of this proof-of-concept study are to (1) determine the safety, acceptability and feasibility of providing HOLOBalance to community dwelling older adults at risk for falls and (2) provide data to support sample size estimates for a future trial., Methods: A single (assessor) blinded pilot randomised controlled proof of concept study. 120 participants will be randomised to receive an 8-week home exercise programme consisting of either: (1) HOLOBalance or (2) The OTAGO Home Exercise Programme. Participants will be required to complete their exercise programme independently under the supervision of a physiotherapist. Participants will have weekly telephone contact with their physiotherapist, and will receive home visits at weeks 0, 3 and 6. Outcome measures of safety, acceptability and feasibility, clinical measures of balance function, disability, balance confidence and cognitive function will be assessed before and immediately after the 8 week intervention. Acceptability and feasibility will be explored using descriptive statistics, and trends for effectiveness will be explored using general linear model analysis of variance., Ethics and Dissemination: This study has received institutional ethical approvals in Germany (reference: 265/19), Greece (reference: 9769/24-6-2019) and the UK (reference: 19/LO/1908). Findings from this study will be submitted for peer-reviewed publications., Trial Registration Number: NCT04053829., Protocol Version: V.2, 20 January 2020., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus is a life-threatening lung disease of immunocompromised patients. Diagnosis currently relies on non-specific chest CT, culture of the fungus from invasive lung biopsy, and detection of the cell wall carbohydrate galactomannan (GM) in serum or in BAL fluids recovered during invasive bronchoscopy. Urine provides an ideal bodily fluid for the non-invasive detection of pathogen biomarkers, with current urine-based immunodiagnostics for IPA focused on GM. Surrogate protein biomarkers might serve to improve disease detection. Here, we report the development of a monoclonal antibody (mAb), PD7, which is specific to A. fumigatus and related species in the section Fumigati , and which binds to its 18 kDa ribotoxin Asp f I. Using PD7, we show that the protein is secreted during hyphal development, and so represents an ideal candidate for detecting invasive growth. We have developed a lateral-flow device ( Afu -LFD ® ) incorporating the mAb which has a limit of detection of ~15 ng Asp f I/mL urine. Preliminary evidence of the test's diagnostic potential is demonstrated with urine from a patient with acute lymphoid leukaemia with probable IPA. The Afu -LFD ® therefore provides a potential novel opportunity for non-invasive urine-based detection of IPA caused by A. fumigatus ., Competing Interests: C. R. Thornton is a Director of ISCA Diagnostics Ltd. M. Hoenigl has received research funding from Gilead and Pfizer outside of this work. The other authors declare no conflicts of interest.

Bipolar disorder (BD) is common and debilitating and confounding effects of depression history on neural activity in BD are unknown. We aimed to dissociate neural activity reflecting past depression-load vs. present symptom severity using the Course and Outcome of Bipolar Youth (COBY), a prospective longitudinal cohort study of pediatric-onset BD. In n = 54 COBY (18-32 years), we modeled depression scores over time (up to 17.5 years) using a standardized autoregressive moving average (ARMA) model, followed by k-means cluster analysis. N = 36 healthy participants (HC, 20-36 years) were included. Using two factorial analyses, we parsed the impact of ARMA-defined past depression-load on neural activity from the impact of current symptoms on neural activity (p < 0.001, k > 30) and examined relationships with past and present symptoms (ps FDR-corrected). ARMA identified three COBY groups based on past depression-load. ARMA-defined COBY participants with the greatest past depression-load vs. other groups showed greater activity in right temporoparietal junction, thalamus, insula, premotor cortex, left fusiform gyrus, bilateral precuneus and cerebellum. In contrast, BD-COBY participants vs. HC showed greater activity in left hippocampus, dorsolateral prefrontal cortex, and right somatosensory cortex, plus the above thalamus, premotor cortex and cerebellum; activity positively correlated with present symptom severity in most regions. Past depression-load was related to social cognition and salience perception network activity, potentially reflecting heightened attention to socially relevant distracters, while present symptoms were associated with emotion processing and reappraisal network activity, potentially reflecting abnormal emotional experience and regulation. Differentiating aberrant neural activity related to long-term depression vs. present affective symptoms can help target interventions to networks associated with pathophysiological processes, rather than long-term illness effects.

Electronic health record (EHR) log data have shown promise in measuring physician time spent on clinical activities, contributing to deeper understanding and further optimization of the clinical environment. In this article, we propose 7 core measures of EHR use that reflect multiple dimensions of practice efficiency: total EHR time, work outside of work, time on documentation, time on prescriptions, inbox time, teamwork for orders, and an aspirational measure for the amount of undivided attention patients receive from their physicians during an encounter, undivided attention. We also illustrate sample use cases for these measures for multiple stakeholders. Finally, standardization of EHR log data measure specifications, as outlined here, will foster cross-study synthesis and comparative research., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

A recently developed risk calculator for bipolar disorder (BD) accounts for clinical and parental psychopathology. Yet, it is understood that both familial predisposition and early life adversity contribute to the development of BD. How the interplay between these two factors influence emotion and reward processing networks in youth at risk for BD remains unclear. In this exploratory analysis, offspring of BD parents performed emotion and reward processing tasks while undergoing a fMRI scan. Risk calculator score was used to assess risk for developing BD in the next 5 years. Environmental risk was tabulated using the Stressful Life Events Schedule (SLES). Emotion and reward processing networks were investigated for genetic and/or environment interactions. Interaction effects were found between risk calculator scores, negative SLES score and activity in right amygdala and bilateral fusiform gyri during the emotion processing task, as well as activity in the fronto-, striatal, and parietal regions during the reward processing task. Our findings are preliminary; however, they support the unique and interactive contributions of both familial and environmental risk factors on emotion and reward processing within OBP. They also identify potential neural targets to guide development of interventions for youth at greatest risk for psychiatric disorders., Competing Interests: The authors have declared that no competing interests exist.

We aimed to identify markers of future affective lability in youth at bipolar disorder risk from the Pittsburgh Bipolar Offspring Study (BIOS) (n = 41, age = 14, SD = 2.30), and validate these predictors in an independent sample from the Longitudinal Assessment of Manic Symptoms study (LAMS) (n = 55, age = 13.7, SD = 1.9). We included factors of mixed/mania, irritability, and anxiety/depression (29 months post MRI scan) in regularized regression models. Clinical and demographic variables, along with neural activity during reward and emotion processing and gray matter structure in all cortical regions at baseline, were used to predict future affective lability factor scores, using regularized regression. Future affective lability factor scores were predicted in both samples by unique combinations of baseline neural structure, function, and clinical characteristics. Lower bilateral parietal cortical thickness, greater left ventrolateral prefrontal cortex thickness, lower right transverse temporal cortex thickness, greater self-reported depression, mania severity, and age at scan predicted greater future mixed/mania factor score. Lower bilateral parietal cortical thickness, greater right entorhinal cortical thickness, greater right fusiform gyral activity during emotional face processing, diagnosis of major depressive disorder, and greater self-reported depression severity predicted greater irritability factor score. Greater self-reported depression severity predicted greater anxiety/depression factor score. Elucidating unique clinical and neural predictors of future-specific affective lability factors is a step toward identifying objective markers of bipolar disorder risk, to provide neural targets to better guide and monitor early interventions in bipolar disorder at-risk youth.