Protection of hepatocytes from apoptosis by a novel substance from actinomycetes culture medium

A novel substance, #675, found from an Streptomyces sp. SM675 culture medium, dose-dependently stimulates the proliferation of human functional liver cell 4 (FLC4). When FLC4 cells were incubated under conditions without fetal bovine serum (FBS), typical features of apoptotic cell death such as shrinkage and nuclear condensation appeared; high molecular weight (HMW) DNA fragments were found; and caspase-3 and poly (ADP-ribose) polymerase (PARP) proteins were cleaved. When FLC4 cells were incubated with #675 and without FBS, the cells grew healthy, no HMW DNA fragments were found, and caspase-3 and PARP cleavage weakened, suggesting that #675 protects FLC4 cells from apoptosis induced by FBS-deprivation. The quantitative reverse-transcribed polymerase chain reaction did not show differences in PARP or Bcl-2 mRNA expression in FLC4 cells incubated with or without #675, indicating other genes may be involved in this anti-apoptosis effect. These results show that #675 enhances FLC4 proliferation via an apoptosis-inhibition pathway, implying potential pharmacological and clinical applications.     

Correcting signal biases and detecting regulatory elements in STARR-seq data

High-throughput reporter assays such as self-transcribing active regulatory region sequencing (STARR-seq) have made it possible to measure regulatory element activity across the entire human genome at once. The resulting data, however, present substantial analytical challenges. Here, we identify technical biases that explain most of the variance in STARR-seq data. We then develop a statistical model to correct those biases and to improve detection of regulatory elements. This approach substantially improves precision and recall over current methods, improves detection of both activating and repressive regulatory elements, and controls for false discoveries despite strong local correlations in signal.

Gene regulation is of foundational importance to nearly all biological processes, and variation in gene regulatory activity plays a major role in human disease risk (Lee and Young 2013; Parker et al. 2013; Finucane et al. 2015). A major step toward measuring regulatory activity across the human genome has been the development of high-throughput reporter assays such as STARR-seq (Arnold et al. 2013) that allow regulatory element activity to be quantified with high-throughput sequencing rather than with optical detection of a fluorescent or luminescent signal.High-throughput reporter assays create substantial analytical challenges that are distinct from other sequencing-based genomic assays. There is significant local variation in high-throughput reporter assay signal. We show here that, across data from several laboratories, most of that variation can be explained by features of the underlying genomic sequence and experimental procedures rather than by regulatory element activity. For example, nucleotide composition can alter PCR efficiency leading to under- and overrepresentation of some sequences. Meanwhile, highly repetitive sequences often do not align uniquely to the human reference genome, also biasing signal estimates. Additional analytical challenges include that STARR-seq signals can be both positive and negative, reflecting activation and repression, and the boundaries of regulatory elements are typically unknown and must therefore be estimated from the data. Those challenges together impact signal representations, hinder estimation of regulatory element activity, and cause false positives and false negatives when left unaddressed.Taken together, key requirements of statistical methods to analyze STARR-seq data are the ability to identify and estimate the effect of both activating and repressing regulatory elements while also correcting for underlying sequence biases in high-throughput reporter assays. A statistical model was recently introduced that corrects technical biases and detects regulatory elements in STARR-seq, but the model is limited to detecting only activating regulatory elements (Lee et al. 2020). Considering repression is a crucial gene regulation mechanism (Courey and Jia 2001), overlooking repressive elements may limit understanding of gene regulation with STARR-seq. To overcome that challenge, our correcting reads and analysis of differentially active elements (CRADLE) model takes a two-step approach. First, CRADLE uses a generalized linear regression model to estimate and correct major biases that we have identified in STARR-seq data. Next, CRADLE detects regions with statistically significant regulatory activity from the bias-corrected signals while rigorously controlling FDR. In doing so, CRADLE substantially improves the use of STARR-seq by providing a robust estimation of regulatory activity and improved visualization of raw signals.     

Histological discrimination of idiopathic inflammatory bowel disease from other types of colitis.

AIMS--To assess the value of histology in diagnosing inflammatory bowel disease (IBD) in colorectal biopsy specimens. METHODS--Retrospective, double blind evaluation of colorectal biopsy specimens from 41 patients with colitis (28 with ischaemic colitis and 13 with acute self-limited colitis) and 84 patients with IBD (42 with Crohn''s disease and 42 with ulcerative colitis). RESULTS--The features distinguishing IBD from other forms of colitis included distorted architecture, lymphocyte and plasma cell infiltrate, excess of polymorphonuclear leucocytes, polymorphonuclear cryptitis, crypt abscesses, and basal lymphoid aggregates. The features discriminating between Crohn''s disease and ulcerative colitis included an irregular or villous surface, distorted architecture, decrease in mucus content, and polymorphonuclear cryptitis. Using multivariate analysis, 90% of patients with Crohn''s disease and 71% of those with ulcerative colitis were correctly classified, the former being strongly defined by epithelioid granulomas, microgranulomas and isolated giant cells, and the latter best defined by an irregular or villous surface, decrease in mucus content and crypt atrophy. CONCLUSIONS--Examination of colorectal biopsy specimens is a reliable method for diagnosing IBD. In the absence of epithelioid granulomas, microgranulomas and isolated giant cells a diagnosis of Crohn''s disease is based on the absence of histological criteria favouring ulcerative colitis. The histological spectrum of indeterminate colitis remains to be clarified.     

Two novel mutations in the EPM2A gene in a Korean patient with Lafora's progressive myoclonus epilepsy

The progressive myoclonus epilepsy of the Lafora type (LD; MIM 254780) is a rare autosomal recessive disorder characterized by epilepsy, myoclonus, progressive neurological deterioration, and the presence of periodic acid-Schiff-positive polyglucosan inclusions (Lafora bodies). Mutations in the EPM2A gene have recently been found to cause LD and about 30 or more mutations have been reported thus far. LD is relatively common in countries of the Mediterranean Basin, the Middle East, India, and Pakistan. Although a few sporadic cases with the typical LD phenotype have also been reported in the Far East including Korea and Japan, a recent effort to find mutations in Japanese LD families was not successful. In the present study, we report two novel mutations in a Korean girl with LD; a 1-bp insertion mutation (c.223insC; G75fsX107) in exon 1 and a missense mutation (c.559A>G; T187A) in exon 3 of the EPM2A gene. To our knowledge, this is the first report of a genetically confirmed case of LD in Koreans and also in the Far East.     

Image reconstruction of anisotropic conductivity tensor distribution in MREIT: computer simulation study

We describe a novel method of reconstructing images of an anisotropic conductivity tensor distribution inside an electrically conducting subject in magnetic resonance electrical impedance tomography (MREIT). MREIT is a recent medical imaging technique combining electrical impedance tomography (EIT) and magnetic resonance imaging (MRI) to produce conductivity images with improved spatial resolution and accuracy. In MREIT, we inject electrical current into the subject through surface electrodes and measure the z-component Bz of the induced magnetic flux density using an MRI scanner. Here, we assume that z is the direction of the main magnetic field of the MRI scanner. Considering the fact that most biological tissues are known to have anisotropic conductivity values, the primary goal of MREIT should be the imaging of an anisotropic conductivity tensor distribution. However, up to now, all MREIT techniques have assumed an isotropic conductivity distribution in the image reconstruction problem to simplify the underlying mathematical theory. In this paper, we firstly formulate a new image reconstruction method of an anisotropic conductivity tensor distribution. We use the relationship between multiple injection currents and the corresponding induced Bz data. Simulation results show that the algorithm can successfully reconstruct images of anisotropic conductivity tensor distributions. While the results show the feasibility of the method, they also suggest a more careful design of data collection methods and data processing techniques compared with isotropic conductivity imaging.     

Associations Between Thyroid Hormone Levels and Urinary Concentrations of Bisphenol A,F, and S in 6-Year-old Children in Korea

ObjectivesBisphenol A (BPA) is used in the electrical, mechanical, medical, and food industries. Previous studies have suggested that BPA is an endocrine disruptor. Regulation of BPA has led to increased use of bisphenol F (BPF) and bisphenol S (BPS). However, few studies have investigated the associations of BPF and BPS with thyroid dysfunction in children. Our study investigated the associations of prenatal BPA and early childhood BPA, BPF, and BPS exposure with thyroid function in 6-year-old children.MethodsPrenatal BPA concentrations were measured during the second trimester of pregnancy in an established prospective birth cohort. We measured urinary BPA, BPF, and BPS concentrations and thyroid hormone levels (thyroid-stimulating hormone, total T₃, and free T₄) in 6-year-old children (n=574). We examined the associations between urinary bisphenol concentrations and percentage change of thyroid hormone concentrations using multivariate linear regression. We also compared thyroid hormone levels by dividing the cohort according to BPA, BPF, and BPS concentrations.ResultsThe associations between prenatal BPA and total T₃ levels were statistically significant in all models, except for girls when using a crude model. The associations between urinary BPA and BPS concentrations and levels of all thyroid hormones were not statistically significant. However, we observed that lower free T₄ levels (−1.94%; 95% confidence interval, −3.82 to −0.03) were associated with higher urinary BPF concentrations in girls only.ConclusionsOur findings identified significant associations between prenatal BPA exposure and total T₃ levels in all children and between BPF exposure and free T₄ levels in girls only.     

Impact of Game-Based Interventions on Health-Related Outcomes in Hospitalized Older Patients: A Systematic Review

ObjectivesTo examine the effectiveness of game-based interventions compared with usual care on health-related outcomes for acutely hospitalized older patients.DesignSystematic review of randomized controlled trials (RCT) and nonrandomized trials.Setting and ParticipantsAdults aged 65 years or older admitted to an Acute Care for Elderly unit were selected.MeasuresHealth-related outcomes (eg, functional capacity, quality of life, adherence to treatment).ResultsFour RCTs were included in the review. The interventions were based on the implementation of serious-game programs using Nintendo Wii in acute medical patients. Across the included studies, no significant differences were observed between groups on functional capacity and health-related quality of life. Significant differences were found between groups on the adherence to treatment (in favor of the control group), but no differences were obtained in other outcomes such as enjoyment and motivation.Conclusions and ImplicationsIn general, there is very limited evidence for the efficacy to reach conclusions about the effects of game-based interventions on health-related outcomes in acutely hospitalized older patients. Future studies are needed to improve our knowledge in the field; however, we consider that these strategies should be considered in the future complementary to usual care.     

Adolescent Substance Use Behavior Change Through School Intervention Is Improved by Teacher and School Implementation Support Together,Especially for Girls

Prevention Science - An earlier trial of a school-based, preventative intervention, HealthWise South Africa, demonstrated some efficacy in preventing adolescent drinking and smoking in the Western...     

Top 100. Revisión de los artículos más citados sobre cirugía laparoscópica del páncreas

IntroductionThe number of citations is considered as an indirect indicator of the merit of an article, journal or researcher, although it is not an infallible method to determine scientific quality. Our goal is to determine the characteristics of the articles most cited about pancreas and laparoscopy.MethodsWe performed a search of all articles published in any journal about pancreas and laparoscopy until September 2019 and selected the 100 most cited papers. We recorded number of citations, journal, year of publication, quartil, impact factor, institution, country, authors type of paper, type of surgery, topic and area.ResultsThe top 100 citations account 10,970 citations in total. The journal with the most articles is Surgical Endoscopy and 2007 is the year with the highest number of articles in the top 100 citations. The percentage of publications from America and Europe are similar.Case series is the most frequently paper, outcomes/morbidity is the most frequently discussed topic, and distal pancreatectomy is the most frequently type of surgery.ConclusionsThis bibliometric study on pancreas and laparoscopy is conditioned by the time factor, since laparoscopy has arrived later at pancreatic surgery, probably due to the morbidity and mortality associated with pancreatic surgery and the need for a high specialization in this field. The literature is recent and scarce. More and better-quality studies are needed in this field.