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Electrical status epilepticus in sleep (ESES) is an age-related, self-limited epileptic encephalopathy. The syndrome is characterized by cognitive and behavioral abnormalities and a specific EEG pattern of continuous spikes and waves during slow-wave sleep. While spikes and sharp waves are known to result in transient cognitive impairment during learning and memory tasks performed during the waking state, the effect of epileptiform discharges during sleep on cognition and behavior is unclear. There is increasing evidence that abnormalities of coherence, a measure of the consistency of the phase difference between two EEG signals when compared over time, is an important feature of brain oscillations and plays a role in cognition and behavior. The objective of this study was to determine whether coherence of EEG activity is altered during slow-wave sleep in children with ESES when compared to typically developing children. We examined coherence during epochs of ESES versus epochs when ESES was not present. In addition, we compared coherence during slow-wave sleep between typically developing children and children with ESES. ESES was associated with remarkably high coherences at all bandwidths and most electrode pairs. While the high coherence was largely attributed to the spikes and spike-and-wave discharge, activity between spikes and spike-and-wave discharge also demonstrated high coherence. This study indicates that EEG coherence during ESES is relatively high. Whether these increases in coherence correlate with the cognitive and behavioral abnormalities seen in children with this EEG pattern remains to be determined.

Abstract Background The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. Methods This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. Discussion This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. Trial registration This study is registered on Clinicaltrials.gov ( NCT03789825 ).

Abstract Temporal variation in eDNA signals is increasingly explored for understanding community ecology in aquatic habitats. Seasonal changes have been addressed using eDNA sampling, but very little is known regarding short‐term temporal variation that spans hours to days. To address this, we filtered marine water samples from a single coastal site in Denmark every hour for 32 h. We used metabarcoding to target both fish and broader eukaryote diversity and evaluated temporal changes in this marine community. Results revealed variation in fish species richness (15–27) and eukaryote class richness (35–64) across the 32 h of sampling, and we further evaluated sampling efforts needed to reach different levels of diversity saturation. Relative read frequency data for both fish and eukaryotes indicated a clear diel change in community composition, with different communities detected during daylight versus dark hours. The abundance signals in our data reflected biological variation rather than stochastic variation, since replicates taken at the same hour were more similar to each other than those taken at different hours. Our compositional results indicated a dynamic community, rather than a static pool of eDNA—even across a few hours. The fish data showed a daily pattern of relative species abundances, and the uncoupling of fish and broader eukaryote data suggest that variation in eDNA profiles across a single day can provide valuable information reflecting diel changes, at least for highly mobile organism groups. However, our results also point to several pitfalls in current eDNA experimental design, in which samples are taken over large areas without relative time‐consistency or short‐term replication. Our findings shed new light on short‐term variation in coastal eDNA and have wide implications for experimental study design and for incorporating temporality into project conceptualization for future aquatic biodiversity monitoring.

Purpose Patients in intensive care units (ICUs) are at risk of stress-related gastrointestinal (GI) bleeding and stress ulcer prophylaxis (SUP), including proton pump inhibitors, is widely used in the attempt to prevent this. In this secondary analysis of Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) trial, we assessed 1-year outcomes in the pantoprazole vs. placebo groups. Methods In the SUP-ICU trial, 3298 acutely admitted ICU patients at risk of GI bleeding were randomly allocated, stratified for site, to pantoprazole or placebo. In this secondary analysis, we assessed clinically important GI bleedings in ICU and 1-year mortality, health care resource use (e.g. readmission with GI bleeding, use of home care and general practitioner), health care costs, and employment status for the Danish participants using registry data. Results Among the 2099 Danish participants, 2092 had data in the registries; 1045 allocated to pantoprazole and 1047 to placebo. The number of clinically important GI bleedings in ICU was 1.9 percentage points [95% CI 0.3-3.5] lower in the pantoprazole group vs. the placebo group, but none of the 1-year outcomes differed statistically significantly between groups, including total health care costs ([euro]1954 [- 2992 to 6899]), readmission with GI bleeding (- 0.005 admissions [- 0.016 to 0.005]), 1-year mortality (- 0.013 percentage points [- 0.051 to 0.026]), and employment (- 0.178 weeks [- 0.390 to 0.034]). Conclusion Among ICU patients at risk of GI bleeding, pantoprazole reduced clinically important GI bleeding in ICU, but this did not translate into a reduction in 1-year mortality, health care resource use or improvements in employment status., Author(s): Christine Marie Bækø Halling [sup.1], Morten Hylander Møller [sup.2] [sup.3], Søren Marker [sup.2] [sup.3], Mette Krag [sup.4], Jakob Kjellberg [sup.1], Anders Perner [sup.2] [sup.3], Dorte Gyrd-Hansen [sup.5] Author Affiliations: [...]

Temporal partitioning in large carnivores have previously been found to be one of the main factors enabling co-existence. While activity patterns have been investigated separately at artificial waterholes and e.g., game trails, simultaneous comparative analyses of activity patterns at artificial waterholes and game trails have not been attempted. In this study, camera trap data from Maremani Nature Reserve was used to investigate whether temporal partitioning existed in a carnivore guild of four species (spotted hyena, leopard, brown hyena and African wild dog). Specifically, we investigated temporal partitioning at artificial waterholes and on roads and trails an average of 1,412 m away from an artificial waterhole. Activity patterns for the same species at artificial waterholes and roads/game trails were also compared. We found no significant differences in temporal activity between species at artificial waterholes. Temporal partitioning on game trails and roads was only found between spotted hyena (nocturnal) and African wild dog (crepuscular). Between nocturnal species (spotted hyena and leopard) no temporal partitioning was exhibited. Only African wild dog exhibited significantly different activity patterns at waterholes and roads/game trails. This indicates artificial waterholes may be a location for conflict in a carnivore guild. Our study highlights the impact of anthropogenic landscape changes and management decisions on the temporal axis of carnivores. More data on activity patterns at natural water sources such as ephemeral pans are needed to properly assess the effect of artificial waterholes on temporal partitioning in a carnivore guild.

Metformin is the currently accepted first-line treatment for antipsychotic-associated weight gain (AAWG). However, not all patients benefit from metformin. Glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown promise in the management of obesity in the general population, with preliminary evidence supporting efficacy in AAWG. Semaglutide is a weekly injectable GLP-1RA which received recent approval for obesity management and noted superiority over other GLP-1RAs. This study explored the efficacy and tolerability of semaglutide in AAWG among individuals with severe mental illness. A retrospective chart review of patients treated with semaglutide in the Metabolic Clinic at the Center for Addiction and Mental Health (CAMH) between 2019 and 2021 was conducted. Patients failing a trial of metformin (

ABSTRACT There is controversy regarding the association between nonalcoholic fatty liver disease (NAFLD) and osteoporosis. Our study aim was to assess bone mineral density (BMD) in patients with biopsy‐proven NAFLD and examine if the severity of NAFLD affects BMD. A total of 147 adult women (n = 108) and men (n = 39) aged 18–76 years (mean ± standard deviation [SD] age 45.3 ± 12.5) were recruited in this cross‐sectional study and underwent a liver biopsy and dual‐energy X‐ray absorptiometry (DXA). NAFLD activity score (NAS) based on the degree of steatosis, lobular inflammation and hepatocellular ballooning was used to assess NAFLD severity. The majority of subjects, 53%, had steatosis, 25% had nonalcoholic steatohepatitis (NASH) whereas 23% served as control subjects with no evidence of NAFLD. There were no significant differences in the lumbar spine (1.09 ± 0.12, 1.11 ± 0.18, and 1.12 ± 0.15 g/cm2, p = 0.69, in controls, steatosis, and NASH, respectively) or hip BMD (1.10 ± 0.15, 1.12 ± 0.13, and 1.09 ± 0.13 g/cm2, p = 0.48, in controls, steatosis, and NASH, respectively) between the groups. Adjusting for age, gender, body mass index, and diabetes in multiple regression models did not alter the results. There was no correlation between NAS and neither lumbar spine BMD (r = 0.06, p = 0.471), nor hip BMD (r = −0.03, p = 0.716). In conclusion, BMD was similar across the spectrum of NAFLD in both genders and not related to the severity of the underlying histological lesions, suggesting that neither steatosis nor NASH exerts a detrimental effect on BMD in these relatively young patients. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Abstract Background Long‐term exercise induces cardiac remodeling that potentially influences the electrical properties of the heart. Hypothesis/objectives We assessed whether training alters cardiac conduction in Standardbred racehorses. Animals Two hundred one trained and 52 untrained Standardbred horses. Methods Cross‐sectional study. Resting ECG recordings were analyzed to assess heart rate (HR) along with standard ECG parameters and for identification of atrial and ventricular arrhythmias. An electrophysiological study was performed in 13 horses assessing the effect of training on sinoatrial (SA) and atrioventricular (AV) nodal function by sinus node recovery time (SNRT) and His signal recordings. Age and sex adjustments were implemented in multiple and logistic regression models for comparison. Results Resting HR in beats per minute (bpm) was lower in trained vs untrained horses (mean, 30.8 ± 2.6 bpm vs 32.9 ± 4.2 bpm; P = .001). Trained horses more often displayed second‐degree atrioventricular block (2AVB; odds ratio, 2.59; P = .04). No difference in SNRT was found between groups (n = 13). Mean P‐A, A‐H, and H‐V intervals were 71 ± 20, 209 ± 41, and 134 ± 41 ms, respectively (n = 7). We did not detect a training effect on AV‐nodal conduction intervals. His signals were present in 1 horse during 2AVB with varying H‐V interval preceding a blocked beat. Conclusions and Clinical Importance We identified decreased HR and increased frequency of 2AVB in trained horses. In 5 of 7 horses, His signal recordings had variable H‐V intervals within each individual horse, providing novel insight into AV conduction in horses.

With the increasing rate of infections caused by multidrug‐resistant organisms (MDRO), selecting appropriate empiric antibiotics has become challenging. We aimed to develop and externally validate a model for predicting the risk of MDRO infections in patients with cirrhosis. Methods: We included patients with cirrhosis and bacterial infections from two prospective studies: a transcontinental study was used for model development and internal validation (n = 1302), and a study from Argentina and Uruguay was used for external validation (n = 472). All predictors were measured at the time of infection. Both culture‐positive and culture‐negative infections were included. The model was developed using logistic regression with backward stepwise predictor selection. We externally validated the optimism‐adjusted model using calibration and discrimination statistics and evaluated its clinical utility. Results: The prevalence of MDRO infections was 19% and 22% in the development and external validation datasets, respectively. The model's predictors were sex, prior antibiotic use, type and site of infection, MELD‐Na, use of vasopressors, acute‐on‐chronic liver failure, and interaction terms. Upon external validation, the calibration slope was 77 (95% CI.48–1.05), and the area under the ROC curve was.68 (95% CI.61–.73). The application of the model significantly changed the post‐test probability of having an MDRO infection, identifying patients with nosocomial infection at very low risk (8%) and patients with community‐acquired infections at significant risk (36%). Conclusion: This model achieved adequate performance and could be used to improve the selection of empiric antibiotics, aligning with other antibiotic stewardship program strategies. [ABSTRACT FROM AUTHOR]

Background: Feeding intolerance is common in critically ill patients and can lead to malnutrition. Prokinetic agents may be used to enhance the uptake of nutrition. However, the evidence on the effectiveness and safety of prokinetic agents is sparse, and there is a lack of data on their use in intensive care units (ICU). Methods: We will conduct an international 14‐day inception cohort study of 1000 acutely admitted adult ICU patients. Data will be collected from ICU admission and daily during ICU stay for up to 90 days. The primary outcome will be the proportion of ICU patients who receive prokinetic agents. Secondary outcomes include mortality, days alive without life support, days alive out of ICU, days alive out of hospital (all within 90 days) and the number of patients with one or more serious adverse events. Results: We will present data on the use of prokinetic agents descriptively and use Cox regressions with death and ICU discharge as competing events to evaluate the association between patient characteristics and the use of prokinetic agents. We will use extended Cox models with time‐varying covariates and linear regression models to assess the associations between the use of prokinetic agents and the secondary outcomes. Conclusion: The outlined international cohort study will provide valuable epidemiological data on the use of prokinetic agents in adult, acutely admitted ICU patients. [ABSTRACT FROM AUTHOR]

Background: Nosocomial infections contribute significantly to mortality and morbidity in burn patients. Selective decontamination of the digestive tract is an infection prevention measure that has been shown to improve survival in mechanically ventilated intensive care unit (ICU) patients. It has been hypothesized that burn patients may benefit from selective decontamination of the digestive tract. Methods/Design: We will conduct a systematic review with meta‐analysis and trial sequential analysis of randomized clinical trials (RCTs) assessing the patient‐important effects of selective decontamination of the digestive tract in burn patients, as compared with placebo or no intervention/standard of care. The primary outcome will be 30‐day mortality. Secondary outcomes include serious adverse events, anti‐microbial resistance, pneumonia, blood stream infections, ICU‐ and hospital‐free days and 90‐day mortality. We will search the following databases: CENTRAL, MEDLINE, EMBASE, BIOSIS, Web of Science and CINAHL and follow the recommendations provided by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. The certainty of evidence will be assessed according to the GRADE approach: Grading of Recommendations Assessment, Development and Evaluation. Discussion: There is clinical equipoise about the use of selective decontamination of the digestive tract in burn patients. In the outlined systematic review and meta‐analysis, we will assess the desirable and undesirable effects of selective decontamination of the digestive tract in burn patients. [ABSTRACT FROM AUTHOR]

Context People with type 1 diabetes (T1D) are at increased risk of thrombosis compared to the general population; however, the underlying mechanisms remain unclear. Hypoglycemia induced at rest can induce coagulation activation, but little is known about the hemostatic effects of exercise-related hypoglycemia in people with T1D. Objective We compared hemostatic profiles of individuals with T1D with healthy controls and explored hemostatic effects of hypoglycemia, induced with or without exercise, in participants with T1D. Methods Thrombelastography was used for a baseline hemostatic comparison between fifteen men with T1D and matched healthy controls. In addition, the participants with T1D underwent two euglycemic-hypoglycemic clamp days in a randomized, crossover fashion. Hypoglycemia was induced with the participants at rest (Hypo-rest) or during exercise (Hypo-exercise). Thrombelastography provides data on the rate of coagulation activation (R-time), the rate of clot formation (K-time, α-Angle), the maximum clot amplitude (MA), the functional fibrinogen contribution to the clot strength (MA-FF) and the fibrinolysis (LY-30). Results The T1D group exhibited a faster rate of coagulation activation (shorter R-time) and a faster clot formation (greater α-Angle) compared with the controls. During the clamp experiments, Hypo-exercise induced an increased clot strength (MA) with a mean difference from baseline of 2.77 mm (95% CI, 2.04-3.51) accompanied with a decreased fibrinolysis (LY-30) of −0.45 percentage point (−0.60 to −0.29). Hypo-rest resulted in increased functional fibrinogen (MA-FF) of 0.74 mm (0.13-1.36) along with an increased fibrinolysis (LY-30) of 0.54 percentage point (0.11-0.98). Conclusion Individuals with T1D exhibit a hypercoagulable hemostatic profile compared with healthy controls and exercise-related hypoglycemia may increase the susceptibility to thrombosis via both procoagulant and antifibrinolytic effects. [ABSTRACT FROM AUTHOR]

The People's Republic of China ("P.R.C.") is in selective default for refusing to pay back private investors from the Hukuang Railway Bond default of 1911. The P.R.C. is the successor government to the Republic of China ("R.O.C.") and Qing Dynasty. This Comment argues that though it is the successor government, the P.R.C. retains the legal rights and obligations of the former government and is the legal inheritor of these debts. This Comment takes this syllogism one step further and argues that the successor government doctrine is customary international law--applying the lessons from the Russian bond default of 1918. Finally, this comment argues that because the successor government doctrine is customary international law, the P.R.C. is in violation of the 1980 U.S.-Sino investment treaty. This Comment recommends that the U.S. government purchase the debt from private investors and force the P.R.C. to arbitration. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of once‐daily oral semaglutide 50 mg on energy intake, appetite, control of eating and gastric emptying. Methods: A clinical pharmacology, double‐blind study was conducted in 61 adults with obesity randomized to once‐daily oral semaglutide (dose‐escalated to 50 mg) or placebo for 20 weeks. Energy intake was measured during an ad libitum lunch, and participant‐reported appetite ratings and Control of Eating Questionnaire responses were assessed. Gastric emptying was measured using paracetamol absorption following a standardized breakfast. Results: The relative change from baseline in ad libitum energy intake at week 20 (primary endpoint) was −39.2% points (95% confidence interval −59.0%, −19.4%) with semaglutide compared with placebo. Body weight was reduced by 9.8% with semaglutide and by 1.5% with placebo. Semaglutide reduced hunger, increased fullness and satiety, and was associated with fewer food cravings and better control of eating versus placebo. No statistically significant difference in gastric emptying was observed at week 20. Conclusions: In participants with obesity, once‐daily oral semaglutide 50 mg reduced energy intake, body weight and appetite, and improved control of eating. There was no evidence of delayed gastric emptying at week 20, as measured through paracetamol absorption. [ABSTRACT FROM AUTHOR]

Background and Aims: Alpha‐1 antitrypsin deficiency is an inherited disorder caused by alpha‐1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver‐related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium. Methods: Reported alcohol consumption was evaluated in two cohorts: (i) the community‐based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non‐carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals). Cohort (ii) included measurements of carbohydrate‐deficient transferrin (CDT). Results: In both cohorts, no/low alcohol intake was reported by >80% of individuals, while harmful consumption was rare (~1%). Among Pi*MM and Pi*MZ individuals from cohort (i), moderate alcohol consumption resulted in a <30% increased rate of elevated transaminases and ~50% increase in elevated gamma‐glutamyl transferase values, while harmful alcohol intake led to an at least twofold increase in the abnormal levels. In Pi*ZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among Pi*ZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease. Conclusions: Pi*MZ/Pi*ZZ genotype does not seem to markedly aggravate the hepatic toxicity of moderate alcohol consumption. CDT values might be helpful to detect alcohol consumption in those with advanced fibrosis. More data are needed to evaluate the impact of harmful alcohol consumption. [ABSTRACT FROM AUTHOR]

The article focuses on the use of SGLT2 inhibitors in patients with HNF1A-MODY, a type of monogenic diabetes. Topics include the typical treatment regimen for HNF1A-MODY, the observed clinical outcomes from adding SGLT2 inhibitors to existing therapies, and the specific HNF1A genetic variants found in the study participants.