Subependymal giant cell astrocytoma (SEGA) is a World Health Organization (WHO) grade I tumor most commonly seen in the context of the underlying tuberous sclerosis complex (TSC). SEGA in the absence of TSC is exceedingly rare. We report the youngest known case of SEGA in the absence of genetic or phenotypic evidence of TSC with a 10-year follow-up. We discuss the literature surrounding isolated SEGA including an approach to diagnosis, management, and prognosis.

To analyze the etiology, microbiological isolates, and antibiotic susceptibilities of endophthalmitis in pediatric patients.

Patients aged < 18years with culture-positive endophthalmitis in Zhongshan Ophthalmic Center between January 2010 and December 2018 were included retrospectively.

A total of 127 patients (127 eyes) were included, and 108 (85%) had posttraumatic endophthalmitis. Streptococcus (21.4%), coagulase-negative Staphylococcus (14.5%), Aspergillus (6.9%), and Bacillus cereus (5.3%) were the common organisms. The proportion of Streptococcus decreased with age (40.0% in 0-3years, 16.3% in 4-12years, and 6.3% in 13-17years), while coagulase-negative Staphylococcus increased from 5.7% to 18.8%. Overall, fluoroquinolones achieved the highest antibiotic susceptibility rate (> 95%), while the susceptibility of isolated bacteria to tobramycin and cefazolin was only 60.2% and 59.4%, respectively. The susceptibility rates of Gram-positive cocci to cephalosporins were nearly 90%. For Gram-negative bacilli, susceptibility to neomycin was 91.3%.

Trauma was the main etiology for pediatric endophthalmitis. Although Streptococcus was the most prevalent organism in general, the dominant pathogen varied with age, which merits clinical attention. Fluoroquinolones showed the highest antibiotic efficacy; however, commonly used antibiotics tobramycin and cefazolin showed relatively low antibiotic susceptibility. Thus, antibiotic resistance in pediatric populations merits clinical attention.

Trauma was the main etiology for pediatric endophthalmitis. Although Streptococcus was the most prevalent organism in general, the dominant pathogen varied with age, which merits clinical attention. Fluoroquinolones showed the highest antibiotic efficacy; however, commonly used antibiotics tobramycin and cefazolin showed relatively low antibiotic susceptibility. Thus, antibiotic resistance in pediatric populations merits clinical attention.

Inflammatory bowel diseases are associated with an increase in the whole-body protein turnover, thus possibly requiring an additional supply of dietary proteins. Our aim was to evaluate whether increasing dietary protein content could alleviate protein metabolism alterations in the injured splanchnic and peripheral tissues during colitis and spontaneous mucosal healing.

Mice with acute chemically induced colitis received either a normal protein (P14, 14% as energy), a moderately (P30, 30%) and a very high-protein (P53, 55%) diets. At different times after the challenge, protein synthesis rate was determined in tissues using a flooding dose of

C valine.

Colon, liver and spleen protein synthesis rates were significantly increased after colitis induction, while being decreased in the caecum, kidneys and muscle. Contrastingly to the two other diets, P30 diet consumption allowed faster recovery of the animals, and this coincided with a rapid resaturation of the initial protein synthesis in the colon. In thions induced by colitis, that may explain its documented beneficial effect on colon mucosal healing.

Nonalcoholic fatty liver disease (NAFLD) is currently the leading cause of chronic liver disease in developing countries. The pathogenesis is complex, and there is currently no effective treatment. Betaine is an essential intermediate in choline catabolism and an important component of the methionine cycle. Betaine deficiency is associated with NAFLD severity, and its mechanism needs to be further elaborated.

In this study, an NAFLD mouse model was established by feeding ApoE

mice a high-fat diet. The effects of betaine on NAFLD were investigated, including its mechanism.

In this study, after treatment with betaine, blood lipid levels and liver damage were significantly decreased in the NAFLD mouse model. The fat infiltration of the liver tissues of high-fat diet (HFD)-fed mice after betaine administration was significantly improved. Betaine treatment significantly upregulated AMP-activated protein kinase (AMPK), fibroblast growth factor 10 (FGF10), and adipose triglyceride lipase (ATGL) protein levels both in vivo and in vitro and suppressed lipid metabolism-related genes. Furthermore, the overexpression of FGF10 increased the protein level of AMPK and decreased lipid accumulation in HepG2 cells.

Taken together, the data strongly suggest that betaine significantly prevents high-fat diet-induced NAFLD through the FGF10/AMPK signaling pathway in ApoE

mice.

Taken together, the data strongly suggest that betaine significantly prevents high-fat diet-induced NAFLD through the FGF10/AMPK signaling pathway in ApoE-/- mice.

To explore the association of both plasma vitamin D and K concentrations with all-cause mortality, cardiovascular mortality, and cardiovascular events in the general population.

We studied 4742 participants of the Prevention of REnal and Vascular ENd-Stage Disease (PREVEND) Study. At baseline, vitamin D and K status was determined by measurement of 25-hydroxyvitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), respectively. Patients were categorized into 25(OH)D < 50 or ≥ 50nmol/L and dp-ucMGP < 361 or ≥ 361pmol/L with 25(OH)D > 75nmol/L and dp-ucMGP < 361pmol/L as reference. Cause of death was coded according to International Classification of Diseases 9&10 codes from the 2001-2003 examination until date of death/event or censoring date (January 1st, 2017).

Mean age was 52.6 ± 11.9years and 2513 (53%) were female. During a median of 14.2year follow-up, 620 participants died of which 142 were due to cardiovascular causes. Combined low vitamin D and K stand K supplementation on clinical outcomes.A case-control study was done to decipher whether the FRAX tool was useful in India. Several values around the mean and median of the FRAX score of the case group were assessed to calculate sensitivity, specificity, positive predictive value, negative predictive value, Youden’s index and odds ratio, and to detect high-risk individuals.

The Fracture Risk Assessment Tool (FRAX) appears useful to diagnose fragility fractures. The study aims to answer whether the FRAX tool has utility in India.

One hundred ten cases with a history of recent fragility fractures and 84 controls with no fractures were included in the study. FRAX scores without bone mineral density (BMD), and also with it, of participants were calculated. Several cutoff FRAX scores were chosen around mean and median FRAX score of cases. The odds ratio was calculated along with sensitivity, specificity, positive predictive value, negative predictive value and Youden’s index. The most ideal cutoff was chosen to construct a hypothetical model to detect individuals at high risk.

The FRAX score with BMD and without BMD exhibited relatively high specificity and moderate to low sensitivity implying that FRAX scores above cutoff have diagnostic value. Cutoffs at which FRAX score without BMD exhibited high specificity (> 90%) were chosen to construct a hypothetical model. Patients with FRAX score without BMD in the intermediate range be advised dual-energy X-ray absorptiometry (DEXA) followed by recalculation of FRAX score with BMD. DEXA scan T score less than - 2.5 or FRAX score with BMD above the cutoff at which specificity was high (> 80%) were included to construct the hypothetical model. Patients with low FRAX score could be followed up. The hypothetical model was applied to the case group to analyse its detection potential.

FRAX has utility in India. It cuts the cost of screening and limits the use of expensive investigation.

FRAX has utility in India. It cuts the cost of screening and limits the use of expensive investigation.Mandatory measurement and disclosure of outcome measures are commonly used policy tools in healthcare. The effectiveness of such disclosures relies on the extent to which the new information produced by the mandatory system is internalized by the healthcare organization and influences its operations and decision-making processes. We use panel data from the Japanese National Hospital Organization to analyze performance improvements following regulation mandating standardized measurement and peer disclosure of patient satisfaction performance. Drawing on value of information theory, we document the absolute value and the benchmarking value of new information for future performance. Controlling for ceiling effects in the opportunities for improvement, we find that the new patient satisfaction measurement system introduced positive, significant, and persistent mean shifts in performance (absolute value of information) with larger improvements for poorly performing hospitals (benchmarking value of information). Our setting allows us to explore these effects in the absence of confounding factors such as incentive compensation or demand pressures. The largest positive effects occur in the initial period, and improvements diminish over time, especially for hospitals with poorer baseline performance. Our study provides empirical evidence that disclosure of patient satisfaction performance information has value to hospital decision makers.

We aimed to explore the relationship between the magnetic resonance imaging (MRI) radiomic score (rad-score) and the grades of non-functioning pancreatic neuroendocrine tumors (NF-pNETs) and evaluate the potential of the calculated MRI rad-score to differentiate grade 1 from grade 2/3 NF-pNETs.

This retrospective study assessed 157 patients with surgically resected, pathologically confirmed NF-pNETs who underwent magnetic resonance scans from November 2012 to December 2019. Radiomic features were extracted from arterial and portal venous MRI. The least absolute shrinkage and selection operator method were used to select the features. Multivariate logistic regression models were used to analyze the association between the MRI rad-score and NF-pNET grades. The MRI rad-score performance was assessed based on its discriminative ability and clinical usefulness.

The MRI rad-score, which consisted of seven selected features, was significantly associated with the NF-pNET grades. Every 1-point increase in the rad-score was associated with a 35% increased risk of grade 2/3 disease. The score also showed high accuracy (area under the curve = 0.775). The best cut-off point for maximal sensitivity and specificity was at 0.41. In the decision curves, when the threshold probability was higher than 0.3, the rad-score used in this study to distinguish grades 1 and 2/3 NF-pNETs offered more benefits than the use of a treat-all-patients or a treat-none scheme.

The MRI rad-score showed a significant association with the grades of NF-pNETs. Thus, it may be used as a valuable non-invasive tool for differential NF-pNET grading.

The MRI rad-score showed a significant association with the grades of NF-pNETs. Thus, it may be used as a valuable non-invasive tool for differential NF-pNET grading.Valero-fenbendazole (VAL-FBZ) is a novel hybrid compound with in vitro anthelmintic activity, designed and synthesized to address the global problem of resistance to anthelmintic compounds. This new molecule derives from fenbendazole (FBZ), a well-known commercially available benzimidazole used in veterinary medicine despite its poor water solubility. In this work, we report for the first time a strategy to solve the solubility problems of FBZ and VAL-FBZ by means of self-dispersible nanocrystals (SDNC). Nanocrystals were prepared by media milling followed by a spray-drying step, and a comprehensive and exhaustive structural and physicochemical characterization was carried out, in order to understand the systems and their behavior. The formulation poloxamer 188 (P188)FBZ 11 turned out with the best process yield (53%) and re-dispersability properties, particle size average of 258 nm, and polydispersity index of 0.2 after redispersion in water. The dissolution profile showed a markedly increased dissolution rate compared with the simple mixture of the components (80% FBZ dissolved in 15 min from the SDNC vs 14% from the control formulation). FTIR spectroscopy, thermal analysis, and X-Ray Powder Diffraction (XRPD) studies showed no chemical interactions between components and an extensive confocal Raman microscopy analysis of the formulations showed very homogeneous spatial distribution of components in the SDNC samples. This manufacturing process was then successfully transferred for preparing and characterizing VAL-FBZP188 (11) SDNC with similar results, suggesting the promising interest of a novel anthelmintic with improved biopharmaceutical behavior. In conclusion, new FBZ and VAL-FBZ SDNC with improved dissolution rate were successfully prepared and characterized. Graphical abstract.Few reports have described the prognostic value of measuring both B-type natriuretic peptides (BNP) and high-sensitivity troponin T (hs-TnT) in pediatric patients with complex congenital heart disease (CHD) undergoing surgery. We assessed demographic, hemodynamic, and laboratory data, including BNP and hs-TnT levels, for the prediction of cardiac adverse events in 85 patients. Cardiac adverse events were defined as death, cardiac arrest, worsening heart failure requiring inotropic agents and/or respiratory support, and unscheduled surgery/intervention either within or after 12 months of surgery. There were 17 cardiac adverse events. Of the demographic variables, low birth weight ( less then  2500 g Odds ratio [OR], 5.97; 95% confidential interval [CI] 1.48-24.0; p = 0.001) and Ross/New York Heart Association [NYHA] class (≥ 2.0) (OR 12.7; 95% CI 3.08-52.7; p = 0.0004) were strongly association with cardiac adverse events. Among hemodynamic and laboratory variables, preoperative BNP (OR 14.04; 95% CI 2.15-91.7; p = 0.001) and hs-TnT levels (OR 16.66; 95% CI 2.27-122; p = 0.002) were found to be independent risk factors. Receiver operating characteristic analysis determined BNP and hs-TnT levels of 60.9 pg/mL and 0.025 ng/mL, respectively, to be markers of high risk. Kaplan-Meier analysis demonstrated significant differences in the freedom from cardiac adverse events between Group A (BNP or hs-TnT elevated, n = 26) and Group B (both biomarkers elevated, n = 19; log-rank, p  less then  0.001). In conclusion, low birth weight ( less then  2500 g) and Ross/NYHA class ≥ 2.0 are strongly associated with cardiac adverse events. Preoperative BNP and hs-TnT also provide prognostic information in patients with complex CHD scheduled for surgery. Using both markers in combination predicts cardiac adverse events better than using either separately.A model consisting of quantitative fingerprinting integrated with fundamental statistical analysis was established to carry out quality control analysis of Shuang-huang-lian (SHL) oral liquid. The quantitative fingerprinting approach was developed by systematic investigation of the chromatographic condition and optimization of a gradient using a complex sample analysis software system (CSASS). Five pivotal components from three traditional Chinese medicines of SHL oral liquid were determined at dual wavelengths, including phillyrin, baicalin, chlorogenic acid, neochlorogenic acid and cryptochlorogenic acid. Among them, neochlorogenic acid and cryptochlorogenic acid were quantified by quantitative analysis of multi-components with a single marker (QAMS) method. Further, the developed quantitative fingerprinting approach was validated. Good linearity with correlation coefficients (R2) higher than 0.9999 were achieved for phillyrin, baicalin and chlorogenic acid. Recoveries of the three analytes were between 96% and 108%. Relative standard deviation (RSD) values were below 3% regarding the stability and intra-day and inter-day precision. Besides, the feasibility of the QAMS method was verified by an external standard method (ESM) using 18 batches of SHL oral liquid. Fifty-nine batches of SHL oral liquid from nine manufacturers were then analyzed. Effective distinction was realized based on a linear principal component analysis (linear-PCA) model by the combination of the quantitative data and chromatographic fingerprinting. The linear-PCA model based on quantitative chromatographic fingerprinting exhibited great advantage over conventional similarity analysis to distinguish between different samples. The strategy provided a particularly simple and effective approach for quality evaluation of SHL oral liquid from various manufacturers. Graphical abstract.A highly multiplexed liquid chromatography mass spectrometry-multiple reaction monitoring (MRM)-based assay has been developed for evaluating 107 candidate immune biomarkers in both hemocytes and plasma of the zebra mussel Dreissena polymorpha. The Scout-MRM strategy was employed for the first time, shortening the implementation of a targeted MRM bottom-up proteomics assay using selected immune protein-related peptides identified by shotgun discovery proteogenomics. This strategy relies on spiking scout peptides during the discovery phase and using them to build and deploy the MRM targeted proteomics method. It proved to be highly relevant, since about 90% of the targeted peptides and proteins were monitored and rapidly measured in both hemocyte and plasma samples. The sample preparation protocol was optimized by evaluating the digestion efficiency of tryptic peptides over time. The accuracy and precision of 50 stable isotope-labeled peptides were evaluated for use as internal standards. Finally, the specificity of the transitions was thoroughly assessed to ensure the reliable measurement of protein biomarkers. Several analytical and biological validation criteria were evaluated across hemocytes and plasma samples exposed ex vivo to biological contaminants, resulting in the validation of two Scout-MRM assays for the relative quantitation of 85 and 89 proteins in hemocytes and plasma, respectively. Graphical abstract.This research has several purposes First to assess the bacterial and fungal minimum inhibitory concentration of Origanum Syriacum essential oil. Second to quantify its bactericidal and fungicidal minimal concentration against S. aureus, S. mutans, and C. albicans found in denture stomatitis. The third purpose is to look at the influence of three different soils (Annaya, Bhanin and Michrif) on the essential oils composition. Three essential oils were extracted by hydro-distillation from three different Origanum Syriacum plant origins. Bioassays were conducted using a broth microdilution methods. Gas Chromatography analysis was used to calculate the abundance of most components in each essential oil. Post hoc tests assessed antimicrobial effects between ecotypes while Pearson’s test correlated the different components and their antimicrobial efficiency (α  less then  0.05). All tested essential oils were efficient against all microorganisms. Origanum Syriacum essential oils derived from Annaya and Bhanin soils showed a superior antimicrobial activity compared to the Michrif one. The most abundant component and most efficient among all essential oils constituents was carvacrol. It can be concluded that Origanum Syriacum essential oils have an antimicrobial activity, which depends on the ecotype, its origin and its composition. They might be used to start a clinical trial for the treatment of denture stomatitis.(-)-Δ-9-tetrahydrocannabinol ((-)-Δ-9-THC) is the main psychoactive constituent in cannabis. During phase I metabolism, it is metabolized to (-)-11-hydroxy-Δ-9-tetrahydrocannabinol ((-)-11-OH-Δ-9-THC), which is psychoactive, and to (-)-11-nor-9-carboxy-Δ-9-tetrahydrocannabinol ((-)-Δ-9-THC-COOH), which is psychoinactive. It is glucuronidated during phase II metabolism. The biotransformation of (-)-Δ-9-tetrahydrocannabinol-glucuronide ((-)-Δ-9-THC-Glc) and (-)-11-nor-9-carboxy-Δ-9-tetrahydrocannabinol-glucuronide ((-)-Δ-9-THC-COOH-Glc) is well understood, which is mainly due to the availability of commercial reference standards. Since such a standardized reference is not yet available for (-)-11-hydroxy-Δ-9-tetrahydrocannabinol-glucuronide ((-)-11-OH-Δ-9-THC-Glc), its biotransformation is harder to study and the nature of the glucuronide bonding-alcoholic and/or phenolic-remains unclear. Consequently, the aim of this study was to investigate the biotransformation of (-)-11-OH-Δ-9-THC-Glc in vitro as well as inic glucuronide in vitro and in vivo. (-)-11-OH-Δ-9-THC-Glc is the first reference standard for direct identification and quantification. This enables future research to answer the question whether phenolic or alcoholic glucuronidation forms the predominant way of metabolism.Coupling elemental mercury (Hg0) oxidation, autotrophic denitrifying sulfur oxidation, and sulfur disproportionation offers technological potential for simultaneous Hg0 and nitric oxide (NO) removal. This study shed light on simultaneous demercuration and denitration of flue gas by a sulfur-oxidizing membrane biofilm reactor (MBfR). Removal efficiency of Hg0 and NO attained 92% and 83%, respectively in long-term operation. Taxonomic and metagenomic study revealed that a tremendous variety of Hg0-oxidizing bacteria (MOB) (Thiobacillus, Truepera, etc.), denitrifying/sulfur-oxidizing bacteria (DSOB) (Thioalkalivibrio, Thauera, etc.), sulfur-disproportionating bacteria (SDB) (Desulfobulbus, Desulfomicrobium, etc.), and multi-functional bacteria (Halothiobacillus, Thiobacillus, etc.) significantly increased in abundance during growth under feeding of Hg0 and NO in simulated flue gas. The comprehensive employment of sequential chemical extraction processes, inductive coupled mass spectrometry, X-ray diffraction, X-ing bacteria, and sulfur-disproportionating bacteria synergistically accomplished Hg0 and NO removal.A number of limitations exist for production of human granulocyte colony-stimulating factor (G-CSF) in Pichia pastoris. In this study, two different specific growth rates (0.015 h-1, 0.01 h-1) were used sequentially in the mixed substrate feeding period during methanol induction phase to enhance the G-CSF titer in the culture broth. Necessary parameters required for implementing the feeding strategy, such as specific product yield on biomass (YP/X) and maintenance coefficient (m) on glycerol, methanol, and sorbitol were estimated using continuous culture technique. Using this strategy, for the same volumetric productivity, about 20% increase in protein titer was achieved over that obtained from the run carried out at a single pre-set value of 0.015 h-1 alone. Thus, implementation of higher specific growth rate (0.015 h-1) set during initial stages of the methanol induction phase followed by a lower specific growth rate (0.01 h-1) helped in achieving increased protein titers.

Critical incident reporting systems (CIRS) serve to sensitize organizations and individuals to unknown events relevant to patient safety and therefore help in developing safer systems; however, the use and impact of these systems in healthcare has recently been questioned for avariety of reasons, among them unclear and imprecise reporting criteria. Some authors claim that fundamental aspects of successful CIRS have been misunderstood, misapplied or entirely missed during the adaptation to the healthcare context. The aim of this study was the analysis of all reports accumulated over 10years in the German system CIRSmedical Anesthesiology (CIRS-AINS) as abasis for improved reporting guidelines, user training and generation of further hypotheses.

In aretrospective analysis all reports from CIRS-AINS entered between April 2010 and June 2019 were analyzed for structure and content.

Atotal of 6013 reports were filed consisting of 3492 incidents (58.1%), 1734 near misses (28.8%) and 787 others (13.1%). Those of communication for these non-CIRS reports exist. The majority of reports were made by physicians, which is in contrast to international experiences with increased engagement of nursing staff and underlines the need for increased interprofessional collaboration with incident reporting and analysis activities in Germany. Reports containing workload complaints, while constituting important signals on a local level, usually fail to address the idea of learning from others inherent to the philosophy of national IRS.The Make Healthy Normal obesity prevention mass media campaign was implemented in New South Wales, Australia from 2015 to 2018. This study evaluated Phase 2 (2017-18) of that campaign, using three cross-sectional online surveys with men aged 18-54 years (n = 4352) and six focus groups with men aged 35-54 years and parents with children aged 5-12 years (n = 38), reflecting the campaign’s target audiences. We used linear and logistic regressions to examine changes over time in key outcomes, consistent with the campaign’s theorized hierarchy of effects. Focus group data were analysed thematically and integrated with survey results at the interpretation stage. Survey results showed reasonable prompted recognition, although unprompted recall remained low, and there were no consistent, positive shifts in other outcomes, including behaviour. Focus group results suggested that this was because the campaign’s messages, while considered clear and relevant, did not address the constraints participants experienced that made change difficult. Hence, the campaign by itself was unlikely to lead to behaviour change. We need to reconsider the role of campaigns in addressing multi-determined and complex problems. Evaluations should reconsider metrics of success, as they may not immediately result in behaviour change, especially in the absence of complementary policy and environmental strategies.

Socioeconomic, cultural, technological, environment and ecological changes are rapidly transforming how children and young people (CYP) grow up, yet their impacts on CYP are difficult to predict. The traditional ways that Public Health practitioners work may not capture such complex and dynamic change. To address this, Lambeth Council used future scenario thinking.

A literature review looked at political, socioeconomic and other 'transitions’ in the borough. Interviews, focus groups and workshops were held with CYP, parents, carers, local statutory and non-statutory stakeholders about the future for Lambeth CYP in the decade ahead. Themes were analysed to identify which had the potential for the biggest impact or the most uncertainty.

The main transitions were described, 100 stakeholders interviewed, and five 'drivers’ of the future were identified protracted austerity, technological explosion, demographic shift, 'democratic shake-up’ and planetary health. From all these data, four future scenarios were developed 'communities care for themselves’, 'collaborating to care for all’, 'nobody cares’ and 'who cares?’

New insights were gained about promoting more responsibility for, and active participation of CYP. This led to Lambeth’s CYP Plan and the 'Made in Lambeth’ campaign aiming to enlist the community and business in creating a child-friendly borough.

New insights were gained about promoting more responsibility for, and active participation of CYP. This led to Lambeth’s CYP Plan and the 'Made in Lambeth’ campaign aiming to enlist the community and business in creating a child-friendly borough.An analytical method for the detection of 40 benzodiazepines, (±)-zopiclone, zaleplon and zolpidem in blood and urine by solid-phase extraction liquid chromatography-tandem mass spectrometry was developed and validated. Twenty-nine of 43 analytes were quantified in 0.5 mL whole blood for investigating postmortem, drug-facilitated sexual assault (DFSA) and driving under the influence of drugs cases (DUID). The four different dynamic ranges of the seven-point, linear, 1/x weighted calibration curves with lower limits of quantification of 2, 5, 10 and 20 μg/L across the analytes encompassed the majority of our casework encountered in postmortem, DFSA and DUID samples. Reference materials were available for all analytes except α-hydroxyflualprazolam, a hydroxylated metabolite of flualprazolam. The fragmentation of α-hydroxyflualprazolam was predicted from the fragmentation pattern of α-hydroxyalprazolam, and the appropriate transitions were added to the method to enable monitoring for this analyte. Urine samples analytical method was routinely employed in the analysis of >300 samples in our laboratory over the last 6 months.

The postoperative persistence of chylothorax is a fatal complication of paediatric cardiac surgery. There is an urgent need for an effective treatment of chylothorax. This study reports the application of allogenic platelet-rich plasma fibrin glue (PRP-FG) as a conservative therapy before reoperation.

Over a 9-year period, from 2010 to 2019, 27 patients with persistent chylothorax following a cavopulmonary connection, with a mean latency period of 11 days (range 10-15 days), were treated with PRP-FG. These patients were selected because they had not responded positively to initial conservative management plans. The patients were followed up for 9 years.

Twenty-five patients (92%) responded positively to treatment with PRP-FG; 2 patients did not respond to the treatment and died after reoperation. All of the successfully treated patients in follow-up continued to live a healthy life without further complications.

Recalcitrant chylothorax that persists after paediatric cardiac surgery responded positively to treatment with PRP-FG. This technique precluded the need for another operation and significantly decreased the morbidity and mortality rates.

Recalcitrant chylothorax that persists after paediatric cardiac surgery responded positively to treatment with PRP-FG. This technique precluded the need for another operation and significantly decreased the morbidity and mortality rates.

Older adults are susceptible to medication nonadherence, which may signify functional decline. Thus, performance-based proxies of medication-taking behavior may help diagnose dementia. We assessed the Medication Management Ability Assessment’s (MMAA) clinical utility and ecological validity.

This was a retrospective chart review of 180 outpatients (age=72±8years) who completed the MMAA during clinical evaluations. Forty-seven were cognitively normal (CN), 103 had mild cognitive impairment (MCI), and 30 had dementia. Most (136) were independent in medication management, whereas 28 were assisted and 16 were dependent. Kruskal-Wallis tests assessed whether MMAA scores differed by diagnosis and independence. Receiver operating characteristic (ROC) analyses identified diagnostic cut-offs. Classification accuracy estimates were derived.

MMAA performance differed across diagnosis as expected (p’s<.001). Those who were independent in medication management outperformed assisted and dependent counterparts (p’s<.001). Assisted and dependent cases were no different. At a cut-off=23, the MMAA was good-to-strong in distinguishing dementia from CN cases (Sn=0.96, Sp=0.83), dementia from MCI (Sn=0.70, Sp=0.83), and dementia from functionally unimpaired cases (Sn=0.78, Sp=0.83). At a cut-off=27, it had good sensitivity but weaker specificity when distinguishing both MCI and all cognitively impaired patients (MCI and dementia) from CN cases (Sn=0.81, Sp=0.66 and Sn=0.81, Sp=0.72, respectively).

The MMAA has ecological validity and clinical utility in identifying dementia. Its inclusion in neuropsychological practice may be especially useful when medication mismanagement is suspected.

The MMAA has ecological validity and clinical utility in identifying dementia. Its inclusion in neuropsychological practice may be especially useful when medication mismanagement is suspected.RNA-binding protein (RBP) is a class of proteins that bind to and accompany RNAs in regulating biological processes. An RBP may have multiple target RNAs, and its aberrant expression can cause multiple diseases. Methods have been designed to predict whether a specific RBP can bind to an RNA and the position of the binding site using binary classification model. However, most of the existing methods do not take into account the binding similarity and correlation between different RBPs. While methods employing multiple labels and Long Short Term Memory Network (LSTM) are proposed to consider binding similarity between different RBPs, the accuracy remains low due to insufficient feature learning and multi-label learning on RNA sequences. In response to this challenge, the concept of RNA-RBP Binding Network (RRBN) is proposed in this paper to provide theoretical support for multi-label learning to identify RBPs that can bind to RNAs. It is experimentally shown that the RRBN information can significantly improve tjtu.edu.cn/bioinf/iDeepMV for academic use. The code is freely available at http//github.com/uchihayht/iDeepMV.One hallmark of trivalent N-acetylgalactosamine (GalNAc)-conjugated siRNAs is the remarkable durability of silencing that can persist for months in preclinical species and humans. Here, we investigated the underlying biology supporting this extended duration of pharmacological activity. We found that siRNA accumulation and stability in acidic intracellular compartments is critical for long-term activity. We show that functional siRNA can be liberated from these compartments and loaded into newly generated Argonaute 2 protein complexes weeks after dosing, enabling continuous RNAi activity over time. Identical siRNAs delivered in lipid nanoparticles or as GalNAc conjugates were dose-adjusted to achieve similar knockdown, but only GalNAc-siRNAs supported an extended duration of activity, illustrating the importance of receptor-mediated siRNA trafficking in the process. Taken together, we provide several lines of evidence that acidic intracellular compartments serve as a long-term depot for GalNAc-siRNA conjugates and are the major contributor to the extended duration of activity observed in vivo.

Despite its benefits, a major concern regarding antipsychotic treatment is its possible impact on the brain’s structure and function. This study sought to explore the characteristics of white matter structural networks in chronic never-treated schizophrenia and those treated with clozapine or risperidone, and its potential association with cognitive function.

Diffusion tensor imaging was performed on a unique sample of 34 schizophrenia patients treated with antipsychotic monotherapy for over 5 years (17 treated with clozapine and 17 treated with risperidone), 17 never-treated schizophrenia patients with illness duration over 5 years, and 27 healthy control participants. Graph theory and network-based statistic approaches were employed.

We observed a disrupted organization of white matter structural networks as well as decreased nodal and connectivity characteristics across the schizophrenia groups, mainly involving thalamus, prefrontal, and occipital regions. Alterations in nodal and connectivity characal networks supporting cognitive function may benefit from antipsychotic treatment, especially in those treated with risperidone.Invasive group A Streptococcus (GAS) in immunocompetent individuals is largely linked to hypervirulent strains. Congenital immunodeficiencies and those acquired from chronic disease or immunosuppressant drugs also increase risk of severe illness. We recovered GAS from the blood of a patient receiving a biologic inhibitor of IL-6. Growth of this serotype M4 isolate in human blood or a murine bacteremia model was promoted by IL-1 or IL-6 inhibition. Hyperinvasive M1T1 GAS was unaffected by IL-6 in both models. These findings based on a natural experiment introduce IL-6 signaling deficiencies as a risk factor for invasive GAS.

We aimed to estimate the causal effect of health conditions and risk factors on social and socioeconomic outcomes in UK Biobank. Evidence on socioeconomic impacts is important to understand because it can help governments, policy makers and decision makers allocate resources efficiently and effectively.

We used Mendelian randomization to estimate the causal effects of eight health conditions (asthma, breast cancer, coronary heart disease, depression, eczema, migraine, osteoarthritis, type 2 diabetes) and five health risk factors [alcohol intake, body mass index (BMI), cholesterol, systolic blood pressure, smoking] on 19 social and socioeconomic outcomes in 336997 men and women of White British ancestry in UK Biobank, aged between 39 and 72 years. Outcomes included annual household income, employment, deprivation [measured by the Townsend deprivation index (TDI)], degree-level education, happiness, loneliness and 13 other social and socioeconomic outcomes.

Results suggested that BMI, smoking and alcohol ocioeconomic outcomes using Mendelian randomization, with the exceptions of depression, asthma and migraines. This may reflect true null associations, selection bias given the relative health and age of participants in UK Biobank, and/or lack of power to detect effects.

Higher BMI, alcohol intake and smoking were all estimated to adversely affect multiple social and socioeconomic outcomes. Effects were not detected between health conditions and socioeconomic outcomes using Mendelian randomization, with the exceptions of depression, asthma and migraines. This may reflect true null associations, selection bias given the relative health and age of participants in UK Biobank, and/or lack of power to detect effects.

Exclusive e-cigarette use has been shown to be associated with reduced levels of respiratory symptoms relative to smoking combustible cigarettes; this association has been less frequently studied in smokers using advanced-generation e-cigarette devices. Advanced-generation devices generate denser vapor than either early generation or pod-style devices, and engender longer inhalations; these vaping topography patterns may contribute to respiratory symptoms.

In a single-session, cross-sectional study of exclusive e-cigarette users (N = 59) and dual users of e-cigarettes and cigarettes (N = 54), participants completed questionnaires, including the American Thoracic Society Questionnaire (ATSQ) and were videotaped vaping their own device in the lab for 1 hour. Using a hierarchical regression method, we examined whether topography variables, level of nicotine concentration used in their e-cigarette device in the past month, e-cigarette dependence, amount of e-cigarette use in the past month, and smoking statushy, likely accounts for differences in respiratory symptoms between dual users and exclusive vapers.Apelin acts as a tumor promoter in multiple malignant tumors; however, its regulatory mechanism remains unclear. Previous studies have indicated that exosomes are pivotal to mediating tumor progression and metastasis. This study examined whether apelin enhances proliferation and invasion ability of lung cancer cells via exosomal microRNA (miRNA). Lung cancer A549 cells overexpressing apelin and control vector were generated by lentiviral transfection. Exosomes were isolated from the culture supernatant of each cell group and characterized. A-exo and V-exo were, respectively, cocultured with A549 cells, and assays of proliferation, apoptosis, colony formation and invasion were conducted. Exosomal miRNA sequencing (miRNA-seq) was performed on A-exo and V-exo to select a candidate miRNA. It was found that A549 cells absorbed more A-exo than V-exo, and A-exo could promote proliferation, colony formation, migration and invasion of A549 cells more than V-exo. Exosomal miRNA-seq data revealed that miR-15a-5p was markedly lower in A-exo compared with V-exo. Low expression of miR-15a-5p was also found in lung cancer tissues and cell lines, suggesting that miR-15a-5p may have an anti-tumor role. Overexpression of miR-15a-5p in A549 cells was associated with less cell proliferation, migration, invasion and suppressed cell cycle, and lower amounts of CDCA4 (cell division cycle-associated protein 4) indicated that it may be a potential target for miR-15a-5p. This study elucidated a novel regulatory mechanism that apelin may promote proliferation and invasion of lung cancer cells by inhibiting miR-15a-5p encapsulated in exosomes.

The molecular mechanism of action of the Janus kinase (JAK) inhibitor tofacitinib is poorly understood.

Here, we analysed the inhibitory effect of tofacitinib on mucosal and blood T cells from patients with ulcerative colitis (UC). Furthermore tofacitinib treatment was analysed in experimental colitis models and wound healing. Additionally, tofacitinib effects were analysed in bioassays.

Tofacitinib significantly reduced T cell derived inflammatory cytokine production (Th2, Th9, Th17) in patients with active UC. Additionally, impaired expression of the homing receptors alpha4/beta1 and alpha4/beta7 as well as reduced gut homing capacity of T cells in a humanized mouse model of colitis were observed. Tofacitinib suppressed acute and chronic oxazolone colitis compared to untreated wild-type mice associated with downregulation of cytokines produced by Th2, Th9 and Th17 cells. Functionally, tofacitinib induced apoptosis of intestinal epithelial cells and prevented mucosal wound healing in vivo at higher concentration. Thus, our findings suggest that tofacitinib is quite effective in protecting from colitis by inhibition of a bundle of T cell derived cytokines like IL-5, IL-6, IL-9, IL-13 and IL-17A.

Application of tofacitinib emerges as an attractive concept for treatment of chronic intestinal inflammation at lower concentrations, whereas higher concentrations require attention due to prolonged wound healing.

Application of tofacitinib emerges as an attractive concept for treatment of chronic intestinal inflammation at lower concentrations, whereas higher concentrations require attention due to prolonged wound healing.

Fecal microbiota transplantation (FMT) is a recommended treatment for recurrent Clostridioides difficile infection, and there is promise that FMT may be effective for conditions like inflammatory bowel disease (IBD). Previous FMT clinical trials have considered the possibility of a „donor effect”, that is, that FMT material from different donors has different clinical efficacies.

Here we re-evaluate evidence for donor effects in published FMT clinical trials for IBD.

In 10 of 12 published studies, no statistically significant donor effect was detected when rigorously re-evaluating the original analyses. One study had statistically significant separation of microbiota composition of pools of donor stool when stratified by patient outcome. One study reported a significant effect but did not have underlying data available for re-evaluation. When quantifying the uncertainty on the magnitude of the donor effect, confidence intervals were large, including both zero donor effect and very substantial donor effects.

Although we found very little evidence for donor effects, the existing data also cannot rule out the possibility that donor effects are clinically important. Large clinical trials prospectively designed to detect donor effects are likely necessary to determine if donor effects are clinically relevant for IBD.

Although we found very little evidence for donor effects, the existing data also cannot rule out the possibility that donor effects are clinically important. Large clinical trials prospectively designed to detect donor effects are likely necessary to determine if donor effects are clinically relevant for IBD.

Alcohol-related hangover symptoms nausea, headache, stress and anxiety cause globally considerable amount of health problems and economic losses. Many of these harmful effects are produced by alcohol and its metabolite, acetaldehyde, which also is a common ingredient in alcohol beverages. The aim of the present study is to investigate the effect of the amino acid L-cysteine on the alcohol/acetaldehyde related aftereffects.

Voluntary healthy participants were recruited through advertisements. Volunteers had to have experience of hangover and/or headache. The hangover study was randomized, double-blind and placebo-controlled. Nineteen males randomly swallowed placebo and L-cysteine tablets. The alcohol dose was 1.5g/kg, which was consumed during 3h.

The primary results based on correlational analysis showed that L-cysteine prevents or alleviates hangover, nausea, headache, stress and anxiety. For hangover, nausea and headache the results were apparent with the L-cysteine dose of 1200mg and for stress and anxiety already with the dose of 600mg.

L-cysteine would reduce the need of drinking the next day with no or less hangover symptoms nausea, headache, stress and anxiety. Altogether, these effects of L-cysteine are unique and seem to have a future in preventing or alleviating these harmful symptoms as well as reducing the risk of alcohol addiction.

L-cysteine would reduce the need of drinking the next day with no or less hangover symptoms nausea, headache, stress and anxiety. Altogether, these effects of L-cysteine are unique and seem to have a future in preventing or alleviating these harmful symptoms as well as reducing the risk of alcohol addiction.Naozhenning (NZN) granule, a Chinese herbal formula, is widely used to treat craniocerebral trauma and promote functional recovery. In our previous study, the chemical components, as well as the serum metabolites in the male Sprague-Dawley rats of the NZN granule after oral administration were characterized. In this study, the urine metabolites in the male Sprague-Dawley rats were further investigated by ultrahigh-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap high-resolution accurate mass spectrometry. In order to identify the urine metabolites comprehensively, three sample preparation methods were used, including solid-phase extraction, protein precipitation method and solvent partition. Based on the accurate molecular weight and the fragmentation information from the MS spectra, a total of 76 urine metabolites were identified, which including 17 prototypes and 59 metabolites. The results showed that the detected urine metabolites were different for the different pretreatment methods, as some metabolites could only be detected in the particular pretreatment method. In addition, the metabolic processes of the components from NZN granule to the serum and urine were also elucidated and discussed. The results will provide useful information for further studying the relationship between the chemical components and pharmacological activity of NZN granule.

We previously showed the efficacy of bi-anodal transcranial direct current stimulation (tDCS) over the prefrontal cortex (PFC) regions with extracephalic reference placement in improving negative symptoms in schizophrenia. In this ancillary investigation, the effects of this intervention on insight levels, other clinical outcomes, and cardio-respiratory and autonomic functions were examined and the potential of biomarkers for treatment response was explored.

Schizophrenia patients were randomly allocated to receive 10 sessions of bi-anodal tDCS over the PFC regions with extracephalic reference placement (2 mA, 20 minutes, twice daily for 5 weeks) or sham stimulation. We examined, in 60 patients at baseline, immediately after stimulation and at follow-up visits, the insight levels, other clinical outcomes, blood pressure, respiratory rate, heart rate, and heart rate variability.

Insight levels as assessed by the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia aw, without impacting other clinical outcomes and cardio-respiratory/autonomic functions.

Preclinical in vivo studies using omental tissue as a biomaterial for myocardial regeneration are promising and have not previously been collated. We aimed to evaluate the effects of the omentum as a support for bioengineered tissue therapy for cardiac regeneration in vivo.

A systematic scoping review was performed. Only English-language studies that used bioengineered cardio-regenerative tissue, omentum and ischaemic cardiomyopathy in vivo models were included.

We initially screened 1926 studies of which 17 were included in the final qualitative analysis. Among these, 11 were methodologically comparable and 6 were non-comparable. The use of the omentum improved the engraftment of bioengineered tissue by improving cell retention and reducing infarct size. Vascularization was also improved by the induction of angiogenesis in the transplanted tissue. Omentum-supported bioengineered grafts were associated with enhanced host reverse remodelling and improved haemodynamic measurements.

The omentum is a promising support for myocardial regenerative bioengineering in vivo. Future studies would benefit from more homogenous methodologies and reporting of outcomes to allow for direct comparison.

The omentum is a promising support for myocardial regenerative bioengineering in vivo. Future studies would benefit from more homogenous methodologies and reporting of outcomes to allow for direct comparison.

Neuroticism is a strong predictor for a variety of social and behavioral outcomes, but the etiology is still unknown. Our study aims to provide a comprehensive investigation of causal effects of serum metabolome phenotypes on risk of neuroticism using Mendelian randomization (MR) approaches.

Genetic associations with 486 metabolic traits were utilized as exposures, and data from a large genome-wide association study of neuroticism were selected as outcome. For MR analysis, we used the standard inverse-variance weighted (IVW) method for primary MR analysis and 3 additional MR methods (MR-Egger, weighted median, and MR pleiotropy residual sum and outlier) for sensitivity analyses.

Our study identified 31 metabolites that might have causal effects on neuroticism. Of the 31 metabolites, uric acid and paraxanthine showed robustly significant association with neuroticism in all MR methods. Using single nucleotide polymorphisms as instrumental variables, a 1-SD increase in uric acid was associated with approximately 30% lower risk of neuroticism (OR 0.77; 95% CI 0.62-0.95; PIVW = 0.0145), whereas a 1-SD increase in paraxanthine was associated with a 7% higher risk of neuroticism (OR 1.07; 95% CI 1.01-1.12; PIVW = .0145).

Our study suggested an increased level of uric acid was associated with lower risk of neuroticism, whereas paraxanthine showed the contrary effect. Our study provided novel insight by combining metabolomics with genomics to help understand the pathogenesis of neuroticism.

Our study suggested an increased level of uric acid was associated with lower risk of neuroticism, whereas paraxanthine showed the contrary effect. Our study provided novel insight by combining metabolomics with genomics to help understand the pathogenesis of neuroticism.