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Abstract Purple blotch disease is a major fungal disease of Allium cepa L. plants which is caused by the fungus Alternaria porri. The best conditions for the growth of Alternaria porri are temperatures between 22 °C and 25 °C and relatively high humidity. The Hydrotime, Thermal Time, and Hydrothermal Time models were used to measure different parameters of seed germination; therefore, we used them to measure the interactive effects of temperature and water potential on the germination conidia of Alternaria porri. The laboratory experiments were carried out at five constant temperatures, between 5 and 30 °C, and five different water potentials between 0 MPa and − 6 MPa. The germination of Alternaria porri conidia was highest at 25 °C and 0 MPa and lowest at 5 °C and − 6 MPa. The percentage of conidia germination decreased rapidly after 25 oC. Conidia germination was also affected by different water potentials, decreasing at lower water potential. Models based on HTT showed a reasonable fit to the germination and growth rate datasets. The best fitting model for conidia germination (R2 = 0.98491) was based on variable base and maximum temperature as a function of water potential. Based on the TT, HT, and models, the highest and lowest values for θT1 were observed at -6.0 MPa at 30 °C, and 0 MPa at 5 °C and the highest and lowest θT2 values were recorded at -6.0 MPa at 5 °C and 0 MPa at 30 °C while the lowest and highest θH values were recorded at -6.0 MPa at 5 °C and 0 MPa at 25 °C, respectively, for the HTT model, the predicted θHTT average value is 16.32 (MPa°Ch-1). Based on the statistical analysis, the cardinal hydrothermal time constant (θHTT) accurately explains the interactive effect of T and Ψ on the germination of Alternaria porri conidia under different environmental conditions.

Background. Obstetric pessary comprises one of the methods for treatment of isthmic-cervical insufficiency. Despite the variety of pessaries produced, the common purpose of their use consists in preventing premature birth. Various types of pessaries correct different cervical parameters, which is not always taken into account by doctors when choosing a pessary and reduces their potential effectiveness. Objective. To substantiate a differentiated approach to the selection of pessary type for correcting isthmic-cervical insufficiency and preventing preterm birth based on the evaluation of cervical parameters. Methods. A randomized prospective study enrolled 90 pregnant women diagnosed with isthmic-cervical insufficiency (ICD-10 code — О.34.3) at 19–24 weeks of gestation. Of these, 41 women underwent correction of isthmic-cervical insufficiency with an obstetric unloading pessary and 49 women — with a perforated cervical pessary. Transvaginal ultrasound cervicometry evaluated the parameters of the cervix before correcting isthmic-cervical insufficiency and in dynamics (once every 4 weeks) after inserting various types of pessaries. Statistical data processing was carried out using Statistica 10.0 (StatSoft, Tulsa, USA) and MedCalc 10.2.0.0 (MedCalc, Mariakerke, Belgium). The differences were considered to be statistically significant at p

Doxylamine is an over-the-counter first-generation antihistamine used in the treatment of allergies and insomnia. Intentional ingestion is common due to its wide availability. Toxicity most frequently presents as an anticholinergic toxidrome with central effects leading to delirium, psychosis, or seizures, and peripheral effects manifested as tachycardia, dry and warm skin, mydriasis, or urinary retention. First-generation antihistamines can have antagonistic properties against the sodium channels on the cardiac myocytes in supratherapeutic doses. This article reports a polysubstance ingestion of 2 antihistaminergic agents with development of QRS complex widening and a right bundle branch block, which has not been well described in the literature.

Abstract Soil texture is one of the most important elements to consider before planting and tillage. These features affect the product selection and regulate its water permeability. Discrimination of soils by determining soil texture features requires an intense workload and is time-consuming. Therefore, having a powerful tool and knowledge for texture-based soil discrimination could enable rapid and accurate discrimination of soils. This study focuses on presenting new models for 6 different soil sample groups (Soil_1 to Soil_6) based on 12 different machine learning algorithms that can be utilized for various problems. As a result, overall accuracy values were determined as greater than 99.2% (Trilayered Neural Network). The greatest accuracy value was found in Bayes Net (99.83%) and followed by Subspace Discriminant (99.80%). In the Bayes Net algorithm, MCC (Matthews Correlation Coefficient) and F-measure values were obtained as 0.994 and 0.995 for Soil_4 and Soil_6 sample groups while these values were 1.000 for other soil groups. Soil types can visually vary based on their texture, mineral composition, and moisture levels. The variability of this can be influenced by fertilization, precipitation levels, and soil cultivation. It is important to capture the images in soil conditions that are more stable. In conclusion, the present study has proven the feasibility of rapid, non-destructive, and accurate discrimination of soils by image processing-based machine learning.

Abstract The absence of a long COVID (LC) or post-acute sequelae of COVID-19 (PASC) diagnostic has profound implications for research and potential therapeutics given the lack of specificity with symptom-based identification of LC and the overlap of symptoms with other chronic inflammatory conditions. Here, we report a machine-learning approach to LC/PASC diagnosis on 347 individuals using cytokine hubs that are also capable of differentiating LC from chronic lyme disease (CLD). We derived decision tree, random forest, and gradient-boosting machine (GBM) classifiers and compared their diagnostic capabilities on a dataset partitioned into training (178 individuals) and evaluation (45 individuals) sets. The GBM model generated 89% sensitivity and 96% specificity for LC with no evidence of overfitting. We tested the GBM on an additional random dataset (106 LC/PASC and 18 Lyme), resulting in high sensitivity (97%) and specificity (90%) for LC. We constructed a Lyme Index confirmatory algorithm to discriminate LC and CLD.

Abstract Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn’s disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14–29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3–92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p

Abstract The emerging field of cellular agriculture has accelerated the development of cell-cultivated adipose tissue as an additive to enhance the flavor of alternative meat products. However, there has been limited research to evaluate the sensory profile of in vitro-grown tissues compared to conventionally obtained animal fat. This study aimed to investigate the aromatic characteristics of cell-cultivated fat tissue as a flavor enhancer for meat alternatives. Porcine dedifferentiated fat (PDFAT) cells were clonally isolated and differentiated into adipocytes. This cultured adipose tissue was then analyzed alongside native porcine fat using gas chromatography-mass spectrometry (GC/MS) coupled with descriptive sensory analysis by human consumers. This evaluation enabled quantitative and qualitative assessments of volatile compounds released during cooking for both in vitro and in vivo porcine fats. The volatile profiles generated during the cooking process and fatty aroma characteristics reported by sensory consumers were largely similar between the two fat sources, with some differences in select compounds and aroma attributes. Ultimately, the consumers found comparable overall liking scores reported between the conventional and cultured porcine fats. These findings provide valuable sensory evidence supporting the viability of cell-cultivated adipose tissue as a flavor component of meat alternatives, substituting for conventional animal fat.

The COVID-19 pandemic highlighted the need for potent community-based tools to improve preparedness. We developed a community health-safety climate (HSC) measure to assess readiness to adopt health behaviors during a pandemic. We conducted a mixed-methods study incorporating qualitative methods (e.g., focus groups) to generate items for the measure and quantitative data from a February 2021 national survey to test reliability, multilevel construct, and predictive and nomologic validities. The 20-item HSC measure is unidimensional (Cronbach α = 0.87). All communities had strong health-safety climates but with significant differences between communities (F = 10.65; p

Purpose: Post removal may be necessary for many reasons and is inevitable after the re-application of a dental post. The present study investigated the bond strength between root dentin and a re-applied fibre-reinforced composite (FRC) post by a pull-out test. Materials and methods: After root canal treatments of 30 extracted human maxillary canine teeth, post spaces were prepared (10 mm), and FRC posts (Hi-Rem Post; Overfibres, İmola, Italy) were luted with self-adhesive resin cement. The samples were than randomly divided into test and control groups (n = 15 in each). The FRC posts were removed in the test group, and new posts were cemented. The pull-out test (1 mm/minute speed) was used to measure the bond strength. Failure types were determined using a stereomicroscope. Mann-Whitney U, chi-square and Fisher-Freeman-Halton exact tests were used for statistical analysis. Results: The bond strength values of the test (119.5 ± 36.86 N) and control (115.55 ± 55.44 N) groups did not differ significantly (p >.05). In terms of the percentage of failure types, there was a significant difference only in the test group between the mixed failure type and the other failure types (p

The aim of this study was to investigate the effects of acute anaerobic exercise on serum levels of adipokines Zinc-α2-glycoprotein (ZAG), apelin, and lipasin. Eighteen male athletes who actively played soccer and trained at least four days a week, with a mean age of 19.11 ± 2.59 years, body weight of 70.61 ± 8.17 kg, height of 176.0 ± 7.71 cm, sport age of 7.22 ± 2.60 years and BMI of 22.76 ± 1.68 kg/m2 participated in the study. Athletes were subjected to the Running-Based Anaerobic Sprint Test (RAST) for anaerobic performance. Blood samples were collected from the athletes 4 times (at rest, 10 minutes, 60 minutes, and 24 hours after exercise). The results of the study showed that acute anaerobic exercise significantly increased ZAG levels (p 0.05). In conclusion, the findings of this study indicate that acute anaerobic exercise is associated with an increase in ZAG levels, but not apelin or lipasin levels. The observations suggest that ZAG may have a specific response to anaerobic exercise, which provides valuable insight into its potential impact on energy metabolism.

Aminoglycoside nephrotoxicity stands as a primary contributor to the development of acute intrinsic renal failure. Distinctive characteristic associated with this nephrotoxicity is the occurrence of tubular necrosis, which is why it is commonly referred to as acute tubular necrosis. Studies have demonstrated that inhibiting rhoA/rho-kinase pathway is beneficial for kidney damage induced by diabetes and renal ischemia. Comparable pathological conditions can be observed in aminoglycoside nephrotoxicity, like those found in diabetes and renal ischemia. Gentamicin, an aminoglycoside, is known to activate Rho/Rho-kinase pathway. The primary goal of this study is to explore influence of oxidative stress on this pathway by concurrently administering gentamicin and alpha-linolenic acid (ALA) possessing known antioxidant properties. To achieve this, gentamicin (100 mg kg−1) and ALA (70 mg kg−1) were administered to mice for a period of 9 days, and Rho/Rho-kinase pathway was examined by using ELISA. Administration of gentamicin to mice led to an elevation in RhoA and rho-kinase II levels, along with the activity of rho-kinase in kidneys. However, ALA effectively reversed this heightened response. ALA, known for its antioxidant properties, inhibited activation of Rho/Rho-kinase pathway induced by gentamicin. This finding suggests that gentamicin induces nephrotoxicity through oxidative stress.

Abstract Objective Oxygen therapy is used for the treatment of various diseases, but prolonged exposure to high concentrations of O2 is also associated with formation of free radicals and oxidative damage. Methods In the present study we compared α-ketoglutarate dehydrogenase (KGDH) activity and mitochondrial oxidative damage in the hearts of guinea pigs after long-term (17 and 60 h) oxygenation with 100% normobaric O2 and with partially negatively (O2 neg) or positively (O2 posit) ionized oxygen. Results Inhalation of O2 led to significant loss in KGDH activity and thiol group content and accumulation of bityrosines. Inhalation of O2 neg was accompanied by more pronounced KGDH inhibition, possibly due to additional formation of protein-lipid conjugates. In contrast, O2 posit prevented loss in KGDH activity and diminished mitochondrial oxidative damage. Conclusions These findings suggest that oxygen treatment is associated with impairment of heart energy metabolism and support the view that inhalation of O2 posit optimizes the beneficial effects of oxygen therapy.

Abstract Tactile Imagery (TI) remains a fairly understudied phenomenon despite growing attention to this topic in recent years. Here, we investigated the effects of TI on corticospinal excitability by measuring motor evoked potentials (MEPs) induced by single-pulse transcranial magnetic stimulation (TMS). The effects of TI were compared with those of tactile stimulation (TS) and kinesthetic motor imagery (kMI). Twenty-two participants performed three tasks in randomly assigned order: imagine finger tapping (kMI); experience vibratory sensations in the middle finger (TS); and mentally reproduce the sensation of vibration (TI). MEPs increased during both kMI and TI, with a stronger increase for kMI. No statistically significant change in MEP was observed during TS. The demonstrated differential effects of kMI, TI and TS on corticospinal excitability have practical implications for devising the imagery-based and TS-based brain–computer interfaces (BCIs), particularly the ones intended to improve neurorehabilitation by evoking plasticity changes in sensorimotor circuitry.

It is well known that the brain is quite vulnerable to oxidative stress, initiating neuronal loss after ischemia-reperfusion (IR) injury. A potent protective mechanism is ischemic preconditioning (IPC), where proteins are among the primary targets. This study explores redox-active proteins’ role in preserving energy supply. Adult rats were divided into the control, IR, and IPC groups. Protein profiling was conducted to identify modified proteins and then verified through activity assays, immunoblot, and immunohistochemical analyses. IPC protected cortex mitochondria, as evidenced by a 2.26-fold increase in superoxide dismutase (SOD) activity. Additionally, stable core subunits of respiratory chain complexes ensured sufficient energy production, supported by a 16.6% increase in ATP synthase activity. In hippocampal cells, IPC led to the downregulation of energy-related dehydrogenases, while a significantly higher level of peroxiredoxin 6 (PRX6) was observed. Notably, IPC significantly enhanced glutathione reductase activity to provide sufficient glutathione to maintain PRX6 function. Astrocytes may mobilize PRX6 to protect neurons during initial ischemic events, by decreased PRX6 positivity in astrocytes, accompanied by an increase in neurons following both IR injury and IPC. Maintained redox signaling via astrocyte-neuron communication triggers IPC’s protective state. The partnership among PRX6, SOD, and glutathione reductase appears essential in safeguarding and stabilizing the hippocampus.

Abstract Hypertrophic cardiomyopathy (HCM) remains the most common cardiomyopathy in humans and cats with few preclinical pharmacologic interventional studies. Small-molecule sarcomere inhibitors are promising novel therapeutics for the management of obstructive HCM (oHCM) patients and have shown efficacy in left ventricular outflow tract obstruction (LVOTO) relief. The objective of this study was to explore the 6-, 24-, and 48-hour (h) pharmacodynamic effects of the cardiac myosin inhibitor, CK-586, in six purpose-bred cats with naturally occurring oHCM. A blinded, randomized, five-treatment group, crossover preclinical trial was conducted to assess the pharmacodynamic effects of CK-586 in this oHCM model. Dose assessments and select echocardiographic variables were assessed five times over a 48-h period. Treatment with oral CK-586 safely ameliorated LVOTO in oHCM cats. CK-586 treatment dose-dependently eliminated obstruction (reduced LVOTOmaxPG), increased measures of systolic chamber size (LVIDs Sx), and decreased select measures of heart function (LV FS% and LV EF%) in the absence of impact on heart rate. At all tested doses, a single oral CK-586 dose resulted in improved or resolved LVOTO with well-tolerated, dose-dependent, reductions in LV systolic function. The results from this study pave the way for the potential use of CK-586 in both the veterinary and human clinical setting.

Abstract We construct non-linear machine learning (ML) prediction models for systolic and diastolic blood pressure (SBP, DBP) using demographic and clinical variables and polygenic risk scores (PRSs). We developed a two-model ensemble, consisting of a baseline model, where prediction is based on demographic and clinical variables only, and a genetic model, where we also include PRSs. We evaluate the use of a linear versus a non-linear model at both the baseline and the genetic model levels and assess the improvement in performance when incorporating multiple PRSs. We report the ensemble model’s performance as percentage variance explained (PVE) on a held-out test dataset. A non-linear baseline model improved the PVEs from 28.1 to 30.1% (SBP) and 14.3% to 17.4% (DBP) compared with a linear baseline model. Including seven PRSs in the genetic model computed based on the largest available GWAS of SBP/DBP improved the genetic model PVE from 4.8 to 5.1% (SBP) and 4.7 to 5% (DBP) compared to using a single PRS. Adding additional 14 PRSs computed based on two independent GWASs further increased the genetic model PVE to 6.3% (SBP) and 5.7% (DBP). PVE differed across self-reported race/ethnicity groups, with primarily all non-White groups benefitting from the inclusion of additional PRSs. In summary, non-linear ML models improves BP prediction in models incorporating diverse populations.

Introduction: The definitive diagnosis of coronavirus disease-2019 (COVID-19) infection is made by polymerase chain reaction (PCR) tests on nasopharyngeal and oropharyngeal swab samples. However, the presence of viral RNA has also been identified in stool samples. In this study, we aimed to investigate the relationship between severe acute respiratory syndrome-coronavirus-2 positivity in stool and the outcomes of COVID-19 disease. Methods: Fifty-four patients who were hospitalized between April-June 2020 and had positive COVID-19 PCR tests in nasopharyngeal and oropharyngeal swab samples were included in the study. PCR was performed on the stool samples of all patients. In addition, laboratory findings, clinical data, and computed tomography (CT) results of these patients were recorded and analyzed. Results: Among the patients, 13 out of 28 (46.4%) with positive fecal PCR test results were female, whereas 11 out of 26 (46.4%) with negative fecal PCR test results were female. Furthermore, 19 out of 28 patients (67.9%) with positive fecal PCR test results recovered, whereas 23 out of 26 patients (88.5%) with negative fecal PCR test results recovered. Notably, patients with fecal PCR-positive results exhibited more severe dyspnea, higher blood pressure, abnormal CT findings, and elevated D-dimer levels. Moreover, compared with patients with negative PCR results, those with positive fecal PCR results had lower levels of procalcitonin, hemoglobin, hematocrit, and lymphocytes. Conclusion: Considering the relationship between stool PCR positivity and the prognosis of the disease and laboratory test results, routine stool PCR tests may be useful, especially in COVID-19 patients presenting with gastrointestinal symptoms.

Abstract Background Gut dysbiosis has been linked with both HIV infection and diabetes, but its interplay with metabolic and inflammatory responses in diabetes, particularly in the context of HIV infection, remains unclear. Methods We first conducted a cross-sectional association analysis to characterize the gut microbial, circulating metabolite, and immune/inflammatory protein features associated with diabetes in up to 493 women (~ 146 with prevalent diabetes with 69.9% HIV +) of the Women’s Interagency HIV Study. Prospective analyses were then conducted to determine associations of identified metabolites with incident diabetes over 12 years of follow-up in 694 participants (391 women from WIHS and 303 men from the Multicenter AIDS Cohort Study; 166 incident cases were recorded) with and without HIV infection. Mediation analyses were conducted to explore whether gut bacteria–diabetes associations are explained by altered metabolites and proteins. Results Seven gut bacterial genera were identified to be associated with diabetes (FDR-q

The COVID-19 pandemic disproportionately affected persons held in and working in correctional and detention facilities, causing facilities’ traditional priorities to shift when healthcare and public health needs temporarily drove many aspects of operations. During July–August 2022, we interviewed members of health departments and criminal justice organizations to document lessons learned from the COVID-19 response in correctional settings. Participants valued enhanced partnerships, flexibility, and innovation, as well as real-time data and corrections-specific public health guidance. Challenges included cross-sector collaborations, population density, scarcity of equipment and supplies, and mental health. Most participants reported improved relationships between criminal justice and public health organizations during the pandemic. Lessons from COVID-19 can be applied to everyday public health preparedness and emergency response in correctional facilities by ensuring representation of correctional health in public health strategy and practice and providing timely, data-driven, and partner-informed guidance tailored to correctional environments when public health needs arise.

Summary: Background: It is uncertain which biological features underpin the response of rectal cancer (RC) to radiotherapy. No biomarker is currently in clinical use to select patients for treatment modifications. Methods: We identified two cohorts of patients (total N = 249) with RC treated with neoadjuvant radiotherapy (45Gy/25) plus fluoropyrimidine. This discovery set included 57 cases with pathological complete response (pCR) to chemoradiotherapy (23%). Pre-treatment cancer biopsies were assessed using transcriptome-wide mRNA expression and targeted DNA sequencing for copy number and driver mutations. Biological candidate and machine learning (ML) approaches were used to identify predictors of pCR to radiotherapy independent of tumour stage. Findings were assessed in 107 cases from an independent validation set (GSE87211). Findings: Three gene expression sets showed significant independent associations with pCR: Fibroblast-TGFβ Response Signature (F-TBRS) with radioresistance; and cytotoxic lymphocyte (CL) expression signature and consensus molecular subtype CMS1 with radiosensitivity. These associations were replicated in the validation cohort. In parallel, a gradient boosting machine model comprising the expression of 33 genes generated in the discovery cohort showed high performance in GSE87211 with 90% sensitivity, 86% specificity. Biological and ML signatures indicated similar mechanisms underlying radiation response, and showed better AUC and p-values than published transcriptomic signatures of radiation response in RC. Interpretation: RCs responding completely to chemoradiotherapy (CRT) have biological characteristics of immune response and absence of immune inhibitory TGFβ signalling. These tumours may be identified with a potential biomarker based on a 33 gene expression signature. This could help select patients likely to respond to treatment with a primary radiotherapy approach as for anal cancer. Conversely, those with predicted radioresistance may be candidates for clinical trials evaluating addition of immune-oncology agents and stromal TGFβ signalling inhibition. Funding: The Stratification in Colorectal Cancer Consortium (S:CORT) was funded by the Medical Research Council and Cancer Research UK (MR/M016587/1).

Abstract Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood–brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10–14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8–22.2). The median overall survival (OS) was 29 months (95% CI, 25.2–33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

Venous collateral shunting of blood from the splanchnic to systemic venous systems due to portal hypertension increases the pressure in the ventral lingual venous bed. We hypothesized that the appearance of sublingual varices evaluated by pre-endoscopy/bedside visual inspection of ventrum of tongue (VIVOT) might predict the presence of esophageal varices (EVs). Methods: To test this hypothesis, we prospectively enrolled patients with cirrhosis (CP) referred for EV screening for assessment of lingual vasculature after informed consent. Non-cirrhosis control patients were also enrolled. Methods: VIVOT was scored based on the presence of vessels > 2 mm and/or serpiginous veins. VIVOT scores were then correlated with endoscopic findings. Results: A total of 59 patients with cirrhosis (Group 1) were enrolled, as were 62 patients without cirrhosis (Group 2). Group 1 consisted of 100% male patients with mean age 59.5 ± 5.4 years; 39.0% were African American (AA). Group 2 consisted of 86% male patients, 59.0 ± 13 years and 53% AA. Among Group 1 patients, varices were present in 29% (16 esophageal and 3 gastric). There were no demographic differences among Group 1 patients with or without varices. Positive VIVOT scores were associated with EVs on endoscopy in 11 of 16 patients (sensitivity 68.75%). Positive VIVOT findings were present in 8 of 40 patients without EVs (specificity 80%). False-positive VIVOT scores were present in 6 of 62 non-cirrhotic controls. Overall, the positive predictive value among patients with cirrhosis was 59% with a negative predictive value of 84%. Conclusions: VIVOT has modest values in predicting EVs and should not be used alone to stratify patients for endoscopic evaluation when elastography and laboratory tests are available; however, its use in resource-limited settings to identify high-risk patients may be considered.

Abstract The long-term safe disposal of radioactive waste corresponds to a challenging responsibility of present societies. Within deep geological waste disposal concepts, host rocks correspond to the ultimate safety barrier towards the environment. To assess the performance of such barriers over extended time scales, mechanistic information on the interaction between the radiotoxic, long-lived radionuclides like plutonium and the host rock is essential. Chemical imaging based on synchrotron microspectroscopic techniques was used to visualize undisturbed reactive transport patterns of Pu within pristine Opalinus Clay rock material. Pu+V is shown to be progressively reduced along its diffusion path to Pu+IV and Pu+III due to interaction with redox-active clay rock constituents. Experimental results and modeling emphasize the dominant role of electron-transfer reactions determining the mobility of Pu in reactive barrier systems. The effective migration velocity of Pu is controlled by the kinetic rates of the reduction to Pu+IV and Pu+III and the redox capacity of the involved electron donor pools. To advance our predictive capabilities further, an improved understanding of the nature and capacity of redox-active components of the reactive barrier material is fundamental. The findings represent an essential contribution to the evaluation of the long-term safety of potential nuclear waste repositories and have implications regarding the development of effective geological disposal strategies.

Abstract Background Hemolysis is a cardinal feature of hemolytic uremic syndrome (HUS) and during hemolysis excess arginase 1 is released from red blood cells. Increased arginase activity leads to reduced L-arginine, as it is converted to urea and L-ornithine, and thereby reduced nitric oxide bioavailability, with secondary vascular injury. The objective of this study was to investigate arginase release in HUS patients and laboratory models and correlate arginase levels to hemolysis and kidney injury. Methods Two separate cohorts of patients (n = 47 in total) with HUS associated with Shiga toxin-producing enterohemorrhagic E. coli (EHEC) and pediatric controls (n = 35) were investigated. Two mouse models were used, in which mice were either challenged intragastrically with E. coli O157:H7 or injected intraperitoneally with Shiga toxin 2. An in vitro model of thrombotic microangiopathy was developed in which Shiga toxin 2- and E. coli O157 lipopolysaccharide-stimulated human blood cells combined with ADAMTS13-deficient plasma were perfused over glomerular endothelial cells. Two group statistical comparisons were performed using the Mann–Whitney test, multiple groups were compared using the Kruskal–Wallis test followed by Dunn’s procedure, the Wilcoxon signed rank test was used for paired data, or linear regression for continuous variables. Results HUS patients had excessively high plasma arginase 1 levels and activity (conversion of L-arginine to urea and L-ornithine) during the acute phase, compared to remission and controls. Arginase 1 levels correlated with lactate dehydrogenase activity, indicating hemolysis, as well as the need for dialysis treatment. Patients also exhibited high levels of plasma alpha-1-microglobulin, a heme scavenger. Both mouse models exhibited significantly elevated plasma arginase 1 levels and activity. Plasma arginase 1 levels correlated with lactate dehydrogenase activity, alpha-1-microglobulin and urea levels, the latter indicative of kidney dysfunction. In the in vitro model of thrombotic microangiopathy, bioactive arginase 1 was released and levels correlated to the degree of hemolysis. Conclusions Elevated red blood cell-derived arginase was demonstrated in HUS patients and in relevant in vivo and in vitro models. The excessively high arginase levels correlated to the degree of hemolysis and kidney dysfunction. Thus, arginase inhibition should be investigated in HUS.

Objectives: This study aimed to report the demographic and clinical characteristics of diabetic macular edema (DME) patients treated with intravitreal injection (IVI) of anti-vascular endothelial growth factors (anti-VEGF) and provide an overview of outcomes during routine clinical practice in Türkiye. Materials and Methods: This retrospective, real-world study included 1,372 eyes (854 patients) treated with a pro re nata protocol by 21 ophthalmologists from 8 tertiary clinics on the Asian side of the Marmara region of Türkiye (MARMASIA Study Group). Five cohort groups were established by collecting the patients’ baseline and 3, 6, 12, 24, and 36-month follow-up data, where each subsequent cohort may include the previous. Changes in best-corrected visual acuity (BCVA, approximate ETDRS letters) and central macular thickness (CMT, μm), number of visits and IVI, and rates of anti-VEGF switch and intravitreal dexamethasone implant (IDI) combination were evaluated. Results: The 3, 6, 12, 24, and 36-month cohorts included 1372 (854), 1352 (838), 1185 (722), 972 (581), and 623 (361) eyes (patients), respectively. The mean baseline BCVA and CMT were 51.4±21.4 letters and 482.6±180.3 μm. The mean changes from baseline in BCVA were +7.6, +9.1, +8.0, +8.6, and +8.4 letters, and in CMT were -115.4, -140.0, -147.9, -167.3, and -215.4 μm at the 3, 6, 12, 24, and 36-month visits (p

Abstract Dilated cardiomyopathy (DCM) is characterized by decreased systolic function and dilation of one or both ventricles, often leading to heart failure or sudden death. Two 10-month-old sibling Nova Scotia Duck Tolling Retrievers (NSDTR) died acutely with evidence of dilated cardiomyopathy with myocardial fibrosis. Association analysis using two cases and 35 controls identified three candidate regions homozygous in the two cases. Whole genome sequencing identified a frameshift deletion in the LMNA gene (NC_049228.1:g.41688530del, NP_001274080:p.(Asp576ThrfsTer124)). Three retrospectively identified NSDTRs with sudden death before 2 years of age and severe myocardial fibrosis were also homozygous for the deletion. One 5 year old with sudden death and myocardial fibrosis was heterozygous for the deletion. This variant was not identified in 722 dogs of other breeds, nor was it identified to be homozygous in 784 NSDTR. LMNA codes for lamin A/C proteins, which are type V intermediate filaments that provide structural support to the nuclear membrane. In humans, LMNA variants can cause DCM with sudden death as well as diseases of striated muscles, lipodystrophy, neuropathies, and accelerated aging disorders. This frameshift deletion is predicted to affect processing of prelamin A into lamin A. Pedigree analysis in the NSDTR and functional evaluation of heterozygotes is consistent with a predominantly recessive mode of inheritance and possibly low penetrance in heterozygotes in contrast to people, where most pathogenic LMNA variants are dominantly inherited.

Abstract Plutonium (Pu) cycling and mobility in the environment can be impacted by the iron cycle and microbial community dynamics. We investigated the spatial and temporal changes of the microbiome in an iron (Fe)-rich, plutonium-contaminated, monomictic reservoir (Pond B, Savannah River Site, South Carolina, USA). The microbial community composition varied with depth during seasonal thermal stratification and was strongly correlated with redox. During stratification, Fe(II) oxidizers (e.g., Ferrovum, Rhodoferax, Chlorobium) were most abundant in the hypoxic/anoxic zones, while Fe(III) reducers (e.g., Geothrix , Geobacter) dominated the deep, anoxic zone. Sulfate reducers and methanogens were present in the anoxic layer, likely contributing to iron and plutonium cycling. Multinomial regression of predicted functions/pathways identified metabolisms highly associated with stratification (within the top 5%), including iron reduction, methanogenesis, C1 compound utilization, fermentation, and aromatic compound degradation. Two sediment cores collected at the Inlet and Outlet of the pond were dominated by putative fermenters and organic matter (OM) degraders. Overall, microbiome analyses revealed the potential for three microbial impacts on the plutonium and iron biogeochemical cycles: (1) plutonium bioaccumulation throughout the water column, (2) Pu–Fe-OM-aggregate formation by Fe(II) oxidizers under microaerophilic/aerobic conditions, and (3) Pu–Fe-OM-aggregate or sediment reductive dissolution and organic matter degradation in the deep, anoxic waters.

Abstract Gradient porous structures (GPS) are characterized by structural variations along a specific direction, leading to enhanced mechanical and functional properties compared to homogeneous structures. This study explores the potential of mycelium, the root part of a fungus, as a biomaterial for generating GPS. During the intentional growth of mycelium, the filamentous network undergoes structural changes as the hyphae grow away from the feed substrate. Through microstructural analysis of sections obtained from the mycelium tissue, systematic variations in fiber characteristics (such as fiber radii distribution, crosslink density, network density, segment length) and pore characteristics (including pore size, number, porosity) are observed. Furthermore, the mesoscale mechanical moduli of the mycelium networks exhibit a gradual variation in local elastic modulus, with a significant change of approximately 50% across a 30 mm thick mycelium tissue. The structure-property analysis reveals a direct correlation between the local mechanical moduli and the network crosslink density of the mycelium. This study presents the potential of controlling growth conditions to generate mycelium-based GPS with desired functional properties. This approach, which is both sustainable and economically viable, expands the applications of mycelium-based GPS to include filtration membranes, bio-scaffolds, tissue regeneration platforms, and more.

Aim: Disease-related immune dysfunction and/or treatment with immunosuppressive drugs may affect the course of coronavirus disease-2019 (COVID-19) infection in rheumatic patients. The aim of this study was to evaluate the course of COVID-19 infection and predictors of COVID-19 pneumonia in patients with rheumatological disease using biological or targeted therapies. Methods: This cross-sectional study was conducted between April 2022 and July 12, 2022. Demographic and clinical parameters and COVID-19-related data in patients with and without COVID-19 pneumonia were recorded and compared. Logistic regression analyses were performed to identify the predictors of COVID-19-related pneumonia. Results: A total of 110 patients (67 with spondyloarthritis, 25 with rheumatoid arthritis, 8 with familial Mediterranean fever, 5 with Takayasu arteritis, 3 with granulomatosis with polyangiitis, and 2 with Behçet’s disease) were included in the study. The mean age of 110 rheumatic patients was 47.27±12.77 years. Their mean body mass index (BMI) was 29.59±5.59 kg/m2, and 67.3% of them were female. Twenty-one (19.1%) patients had a history of COVID-19 pneumonia. The rates of hypertension (HT), diabetes mellitus, comorbidity status, comorbidity groups, cough, dyspnea, non-healing complaints, and COVID-19 treatment in addition to BMI, the total number of comorbidities, and the number of vaccines after COVID-19 infection were statistically different in the groups with and without pneumonia (for all, p

Objectives:To compare the clinical findings and multimodal imaging of pediatric patients diagnosed with papilledema and pseudopapilledema with those of healthy individuals.Materials and Methods:Ninety children (0.05). The average, nasal, and temporal RNFL thicknesses were significantly higher in the pseudopapilledema group compared with the controls (p

We were tasked by Canada’s COVID-19 Immunity Task Force to describe severe adverse events (SAEs) associated with emergency department (ED) visits and/or hospitalizations in individuals with immune-mediated inflammatory diseases (IMIDs). At eight Canadian centres, data were collected from adults with rheumatoid arthritis (RA), axial spondyloarthritis (AxS), systemic lupus (SLE), psoriatic arthritis (PsA), and inflammatory bowel disease (IBD). We administered questionnaires, analyzing SAEs experienced within 31 days following SARS-CoV-2 vaccination. About two-thirds (63%) of 1556 participants were female; the mean age was 52.5 years. The BNT162b2 (Pfizer) vaccine was the most common, with mRNA-1273 (Moderna) being second. A total of 49% of participants had IBD, 27.4% had RA, 14.3% had PsA, 5.3% had SpA, and 4% had SLE. Twelve (0.77% of 1556 participants) SAEs leading to an ED visit or hospitalization were self-reported, occurring in 11 participants. SAEs included six (0.39% of 1556 participants) ED visits (including one due to Bell’s Palsy 31 days after first vaccination) and six (0.39% of 1556 participants) hospitalizations (including one due to Guillain-Barré syndrome 15 days after the first vaccination). Two SAEs included pericarditis, one involved SLE (considered a serious disease flare), and one involved RA. Thus, in the 31 days after SARS-CoV-2 vaccination in our IMID sample, very few serious adverse events occurred. As SARS-CoV2 continues to be a common cause of death, our findings may help optimize vaccination acceptance.

Objective: SARS-CoV-2 remains the third most common cause of death in North America. We studied the effects of methotrexate and tumor necrosis factor inhibitor (TNFi) on neutralization responses after COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Methods: Prospective data and sera of adults with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and systemic lupus (SLE) were collected at six academic centers in Alberta, Manitoba, Ontario, and Quebec between 2022 and 2023. Sera from two time points were evaluated for each subject. Neutralization studies were divided between five laboratories, and each lab’s results were analyzed separately using multivariate generalized logit models (ordinal outcomes: absent, low, medium, and high neutralization). Odds ratios (ORs) for the effects of methotrexate and TNFi were adjusted for demographics, IMID, other biologics and immunosuppressives, prednisone, COVID-19 vaccinations (number/type), and infections in the 6 months prior to sampling. The adjusted ORs for methotrexate and TNFi were then pooled in random-effects meta-analyses (separately for the ancestral strains and the Omicron BA1 and BA5 strains). Results: Of 479 individuals (958 samples), 292 (61%) were IBD, 141 (29.4%) were RA, and the remainder were PsA, SpA, and SLE. The mean age was 57 (62.2% female). For both the individual labs and the meta-analyses, the adjusted ORs suggested independent negative effects of TNFi and methotrexate on neutralization. The meta-analysis adjusted ORs for TNFi were 0.56 (95% confidence interval (CI) 0.39, 0.81) for the ancestral strain and 0.56 (95% CI 0.39, 0.81) for BA5. The meta-analysis adjusted OR for methotrexate was 0.39 (95% CI 0.19, 0.76) for BA1. Conclusions: SARS-CoV-2 neutralization in vaccinated IMID was diminished independently by TNFi and methotrexate. As SARS-CoV-2 circulation continues, ongoing vigilance regarding optimized vaccination is required.

The extracellular matrix of most bacterial biofilms contains polysaccharides, proteins, and nucleic acids. These biopolymers have been shown to mediate fundamental biofilm-related phenotypes including surface attachment, intercellular adhesion, and biocide resistance. Enzymes that degrade polymeric biofilm matrix components, including glycoside hydrolases, proteases, and nucleases, are useful tools for studying the structure and function of biofilm matrix components and are also being investigated as potential antibiofilm agents for clinical use. Dispersin B is a well-studied, broad-spectrum antibiofilm glycoside hydrolase produced by Aggregatibacter actinomycetemcomitans. Dispersin B degrades poly-N-acetylglucosamine, a biofilm matrix polysaccharide that mediates biofilm formation, stress tolerance, and biocide resistance in numerous Gram-negative and Gram-positive pathogens. Dispersin B has been shown to inhibit biofilm and pellicle formation; detach preformed biofilms; disaggregate bacterial flocs; sensitize preformed biofilms to detachment by enzymes, detergents, and metal chelators; and sensitize preformed biofilms to killing by antiseptics, antibiotics, bacteriophages, macrophages, and predatory bacteria. This review summarizes the results of nearly 100 in vitro and in vivo studies that have been carried out on dispersin B since its discovery 20 years ago. These include investigations into the biological function of the enzyme, its structure and mechanism of action, and its in vitro and in vivo antibiofilm activities against numerous bacterial species. Also discussed are potential clinical applications of dispersin B.

Abstract Background Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined. Methods We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3–4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight). Results Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p

Aim:This study investigated the potential role of serum copeptin, a mediator of acute pain via sympathetic stress stimulation, as a biomarker of varying degrees of migraine-related disability. Specifically, we aimed to analyze whether the serum copeptin level can be used to differentiate migraine types (e.g., with and without aura).Methods:The study population included 80 consecutively consenting adult patients who had migraine attacks and attended the emergency department from June 2020 through November 2020, as well as 80 age- and sex-matched healthy controls. Using the Migraine Disability Assessment Scale (MIDAS), the same medical professional assessed each patient’s level of headache-related disability. Based on their MIDAS scores, the patients were separated into four groups: no disability (score 0-5; group MIDAS-I); mild disability (score 6-10; group MIDAS-II); moderate impairment (score 11-20; group MIDAS-III); and severe disability (score >20; group MIDAS-IV). There were also two categories of migraineurs: those with auras and those without auras. Upon admission, comparisons were made between the groups’ serum copeptin values.Results:In comparison to the control group, the patient group’s serum copeptin levels were noticeably higher (2113.30±206.20 vs. 1383.40±488.40; p

Aim:Urinary tract infection (UTI) is one of the most common bacterial infections in children. Empirical treatment is commenced according to the patient’s characteristics and the antimicrobial susceptibility patterns in the region. Therefore, a determination of antimicrobial resistance patterns has a great importance in effective treatment. The aim of this study was to determine the pathogens which cause UTIs in patients admitted to a university hospital in Izmir and to determine their antimicrobial susceptibility pattern.Materials and Methods:The files of patients aged between 0-18 years, followed up with a diagnosis of UTI, vesicoureteral reflux and neurogenic bladder in Ege University Faculty of Medicine Paediatric Nephrology Unit between February, 2013 and November, 2018 were retrospectively reviewed.Results:A total of 1,126 positive urine cultures from 729 patients (65% female) were included in this study. Gram-negative pathogens constituted 88.2% of the cultures. Escherichia coli (E. coli) was the most commonly isolated bacteria with a prevalence of 59.1%, followed by Klebsiella pneumonia with 17.9%, and Enterococcus faecalis with 8.3% (n=93). Ampicillin, cefuroxime and trimethoprim-sulfamethoxazole with susceptibility rates of 18.6%, 39.6%, 49.0% respectively, constituted the highest resistant antimicrobials to Enterobacteriaceae. Enterococcus spp. showed the highest resistance to gentamycin with 50% resistance in tested cases. Pseudomonas spp. with 64.3% susceptibility showed the highest resistance to piperacillin-tazobactam.Conclusion:This study revealed that bacterial resistance to commonly used antimicrobials in UTI is an important and challenging problem which requires planning.

Aim:Celiac disease is associated with an increased risk of cardiovascular disease due to inflammation and autoimmunity involved in its pathophysiology. We aimed to evaluate vascular involvement in children with celiac disease based on their augmentation index, carotid pulse wave velocity, carotid intima-media thickness, echocardiographic findings, and blood pressure.Materials and Methods:This cross-sectional and controlled study was performed at a single center between 2018 and 2019. The study population consisted of 44 patients with celiac disease who had been on a gluten-free diet for at least one year.Results:We compared celiac patients with a healthy group. While the celiac patients had significantly higher carotid intima media thickness and carotid pulse wave velocity values, there was no difference in the augmentation index values. There was no significant difference in carotid artery intimal medial thickness, augmentation index and carotid pulse wave velocity values between the diet-compliant and non-compliant groups.Conclusion:Although hypertension was not detected, arterial stiffness and carotid intima media thickness measurements were higher in the celiac disease patients compared to the healthy controls. This showed that these parameters can be used in early vascular damage assessment. These measurements, which are non-invasive and repeatable, can be a guide for the monitoring of the development of preclinical atherosclerosis in the follow-up of the pediatric patients diagnosed with celiac disease.

Objective:This study was conducted to evaluate the effect of a two-stage intervention, including sensory stimulation and sleep hygiene based on a nursing model, on the reduction of delirium development in Coronavirus disease-2019 (COVID-19) patients in the intensive care unit (ICU).Materials and Methods:The study was conducted as a pretest-posttest control group and trial model. The sample size of the study was 92 patients with COVID-19, including 43 in the experimental group and 49 in the control group, based on power analysis. The study was conducted in two separate COVID-19 ICUs. Sensory stimulation and sleep hygiene interventions were applied to the patients in the intervention group according to the Living Activities-Based Nursing Model. The intervention was applied to the experimental group until the patients were discharged.Results:It was determined that there was no statistical difference between the experimental and control group patients included in the study in terms of demographic and treatment characteristics and vital and arterial blood gas values (p>0.05). In the study, it was determined that sensory stimulation and sleep hygiene intervention based on the nursing model creates a statistically significant difference in the delirium development levels of the experimental and control group patients (p

Abstract Oxycodone is one of the most widely prescribed and misused opioid painkillers in the United States. Evidence suggests that biological sex and hormonal status can impact drug reward in humans and rodents, but the extent to which these factors can influence the rewarding effects of oxycodone is unclear. The purpose of this study was to utilize place conditioning to determine the effects of sex and female hormonal status on the expression of oxycodone conditioned reward in rats. Gonadally intact adult Sprague-Dawley male and female rats were used to test: (1) whether both sexes express conditioned reward to oxycodone at similar doses, (2) the impact of conditioning session length on oxycodone conditioned reward expression in both sexes, and (3) the influence of female estrous cycle stage on oxycodone conditioned reward expression. Both sexes expressed conditioned reward at the same doses of oxycodone. Increasing the length of conditioning sessions did not reveal an effect of sex and resulted in lower magnitude conditioned reward expression. Importantly however, female stage of estrous cycle significantly influenced oxycodone conditioned reward expression. These results suggest that female hormonal status can impact the rewarding effects of opioids and thus have important implications for prescription opioid treatment practices.

Abstract Background Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk. Methods We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data. Results By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent. Conclusions Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.

Abstract Unlike short-term laboratory experiments, studies at sites historically contaminated with radionuclides can provide insight into contaminant migration behavior at environmentally-relevant decadal timescales. One such site is Pond B, a seasonally stratified reservoir within Savannah River Site (SC, USA) has low levels (μBq L−1) of plutonium in the water column. Here, we evaluate the origin of plutonium using high-precision isotope measurements, investigate the impact of water column geochemistry on plutonium cycling during different stratification periods, and re-evaluate long-term mass balance of plutonium in the pond. New isotopic data confirm that reactor-derived plutonium overwhelms input from Northern Hemisphere fallout at this site. Two suggested mechanisms for observed plutonium cycling in the water column include: (1) reductive dissolution of sediment-derived Fe(III)-(oxyhydr)oxides during seasonal stratification and (2) plutonium stabilization complexed strongly to Fe(III)-particulate organic matter (POM) complexes. While plutonium may be mobilized to a limited extent by stratification and reductive dissolution, peak plutonium concentrations are in shallow waters and associated with Fe(III)-POM at the inception of stratification. This suggests that plutonium release from sediments during stratification is not the dominant mechanism driving plutonium cycling in the pond. Importantly, our analysis suggests that the majority is retained in shallow sediments and may become increasingly recalcitrant.

Abstract Impacts of insecticide use on the health of wild and managed pollinators have been difficult to accurately quantify in the field. Existing designs tend to focus on single crops, even though highly mobile bees routinely forage across crop boundaries. We created fields of pollinator-dependent watermelon surrounded by corn, regionally important crops in the Midwestern US. These fields were paired at multiple sites in 2017–2020 with the only difference being pest management regimes: a standard set of conventional management (CM) practices vs. an integrated pest management (IPM) system that uses scouting and pest thresholds to determine if/when insecticides are used. Between these two systems we compared the performance (e.g., growth, survival) of managed pollinators—honey bees (Apis mellifera), bumble bees (Bombus impatiens)—along with the abundance and diversity of wild pollinators. Compared to CM fields, IPM led to higher growth and lower mortality of managed bees, while also increasing the abundance (+ 147%) and richness (+ 128%) of wild pollinator species, and lower concentrations of neonicotinoids in the hive material of both managed bees. By replicating realistic changes to pest management, this experiment provides one of the first demonstrations whereby tangible improvements to pollinator health and crop visitation result from IPM implementation in agriculture.

Abstract In socially monogamous prairie voles (Microtus ochrogaster), parental behaviors not only occur in mothers and fathers, but also exist in some virgin males. In contrast, the other virgin males display aggressive behaviors towards conspecific pups. However, little is known about the molecular underpinnings of this behavioral dichotomy, such as gene expression changes and their regulatory mechanisms. To address this, we profiled the transcriptome and DNA methylome of hippocampal dentate gyrus of four prairie vole groups, namely attacker virgin males, parental virgin males, fathers, and mothers. While we found a concordant gene expression pattern between parental virgin males and fathers, the attacker virgin males have a more deviated transcriptome. Moreover, numerous DNA methylation changes were found in pair-wise comparisons among the four groups. We found some DNA methylation changes overlapping with transcription differences, across gene-bodies and promoter regions. Furthermore, the gene expression changes and methylome alterations are selectively enriched in certain biological pathways, such as Wnt signaling, which suggest a canonical transcription regulatory role of DNA methylation in paternal behavior. Therefore, our study presents an integrated view of prairie vole dentate gyrus transcriptome and epigenome that provides a DNA epigenetic based molecular insight of paternal behavior.

The purpose of this work was to provide a simple method to determine reactive strength during the 6-meter timed hop test (6mTH) and evaluate its association with isokinetic peak torque in patients following anterior cruciate ligament reconstruction (ACLR). Twenty-nine ACLR patients who were at least four months from surgery were included in this analysis. Participants were brought into the laboratory on one occasion to complete functional testing. Quadriceps and hamstring isokinetic testing was completed bilaterally at 60, 180, and 300 deg∙s-1, using extension peak torque from each speed as the outcome measure. The 6mTH was completed bilaterally using a marker-based motion capture system, and reactive strength ratio (RSR) was calculated from the vertical velocity of the pelvis during the test. An adjustment in RSR was made using the velocity of the 6mTH test to account for different strategies employed across participants. Repeated measures correlations were used to determine associations among isokinetic and hop testing variables. A two-way mixed analysis of variance was used to determine differences in isokinetic and hop testing variables between operated and non-operated legs and across male and female participants. Moderate positive associations were found between RSR (and adjusted RSR) and isokinetic peak torque at all speeds (r = .527 to .577). Mean comparisons showed significant main effects for leg and sex. Patients showed significant deficits in their operated versus non-operated legs in all isokinetic and hop testing variables, yet only isokinetic peak torque and timed hop time showed significant differences across male and female groups. Preliminary results are promising but further development is needed to validate other accessible technologies available to calculate reactive strength during functional testing after ACLR. Pending these developments, the effects of movement strategies, demographics, and levels of participation on RSR can then be explored to translate this simple method to clinical environments.

IntroductionDue to the health consequences arising from climate change, medical students will inevitably interact with affected patients during their training and careers. Accordingly, medical schools must incorporate education on the impacts of climate change on health and equity into their curricula. We created a curricular thread called "Climate Change, Health, and Equity" in the first-year preclinical medical program to teach foundational concepts and foster self-reflection and critical consciousness.MethodsThe authors developed a continuum of practice including administrators, educators and faculty members, students, and community partners to plan and design curricular activities. First-year medical students at Duke University School of Medicine participated in seven mandatory foundational lectures and two experiential learning opportunities in the local community. Following completion of activities, students wrote a critical reflection essay and completed a self-directed learning exercise. Essays were evaluated using the REFLECT rubric to assess if students achieved critical reflection and for thematic analysis by Bloom's Taxonomy.ResultsAll students (118) submitted essays. A random sample of 30 (25%) essays underwent analysis. Evaluation by the REFLECT rubric underscored that all students were reflecting or critically reflecting on thread content. Thematic analysis highlighted that all students (30/30, 100%) were adept at identifying new areas of medical knowledge and connecting concepts to individual experiences, institutional practices, and public health and policy. Most students (27/30; 90%) used emotionally laden words, expressing negative feelings like frustration and fear but also positive sentiments of solidarity and hope regarding climate change and effects on health. Many students (24/30; 80%) expressed actionable items at every level including continuing self-directed learning and conversing with patients, minimizing healthcare waste, and advocating for climate-friendly policies.ConclusionAfter participating in the curricular thread, most medical students reflected on cognitive, affective, and actionable aspects relating to climate change, health, and equity.

BackgroundNeonatal jaundice (NNJ) is a major contributor to childhood morbidity and mortality. As many infants are discharged by 24 hours of age, mothers are key in detecting severe forms of jaundice. Mothers with limited knowledge of NNJ have a hard time identifying these infants who could go on to have the worst outcomes. This study aimed to determine the effect of a jaundice education package delivered to mothers prior to hospital discharge on maternal knowledge after discharge.MethodsThis was a before and after interventional study involving an education package delivered through a video message and informational voucher. At 10-14 days after discharge, participants were followed up via telephone to assess their post-intervention knowledge. A paired t-test was used to determine the effectiveness of the intervention on knowledge improvement. Linear regression was used to determine predictors of baseline knowledge and of change in knowledge score.ResultsOf the 250 mothers recruited, 188 were fit for analysis. The mean knowledge score was 10.02 before and 14.61 after the intervention, a significant difference (pConclusionMaternal knowledge of jaundice can be increased using a simple educational intervention, especially in settings where the burden of detection often falls on the mother. Further study is needed to determine the impact of this intervention on care seeking and infant outcomes.

BackgroundExpression of angiotensin-converting enzyme (ACE)-2 and co-factors like furin, play key-roles in entry of SARS-CoV-2 into host cells. Furin is also involved in oral carcinogenesis. We investigated their expression in oral pre-malignant/malignant epithelial pathologies to evaluate whether ACE2 and furin expression might increase susceptibility of patients with these lesions for SARS-CoV-2 infection.MethodsStudy included normal oral mucosa (N = 14), epithelial hyperplasia-mild dysplasia (N = 27), moderate-to-severe dysplasia (N = 24), squamous cell carcinoma (SCC, N = 34) and oral lichen planus (N = 51). Evaluation of ACE2/furin membranous/membranous-cytoplasmic immunohistochemical expression was divided by epithelial thirds (basal/middle/upper), on a 5-tier scale (0, 1-weak, 1.5 -weak-to-moderate, 2-moderate, 3-strong). Total score per case was the sum of all epithelial thirds, and the mean staining score per group was calculated. Real time-polymerase chain reaction was performed for ACE2-RNA. Statistical differences were analyzed by One-way ANOVA, significance at pResultsAll oral mucosa samples were negative for ACE2 immuno-expression and its transcripts. Overall, furin expression was weakly present with total mean expression being higher in moderate-to-severe dysplasia and hyperplasia-mild dysplasia than in normal epithelium (p = 0.01, each) and SCC (p = 0.008, p = 0.009, respectively).ConclusionsOral mucosa, normal or with epithelial pathologies lacked ACE2 expression. Furin was weak and mainly expressed in dysplastic lesions. Thus, patients with epithelial pathologies do not seem to be at higher risk for SARS-CoV-2 infection. Overall, results show that oral mucosae do not seem to be a major site of SARS-CoV-2 entry and these were discussed vis-à-vis a comprehensive analysis of the literature.