Metabolic Database Research Articles

Metabolic networks of the Nicotiana genus in the spotlight: content, progress and outlook.

Manually curated metabolic databases residing at the Sol Genomics Network comprise two taxon-specific databases for the Solanaceae family, i.e. SolanaCyc and the genus Nicotiana, i.e. NicotianaCyc as well as six species-specific databases for Nicotiana tabacum TN90, N. tabacum K326, Nicotiana benthamiana, N. sylvestris, N. tomentosiformis and N. attenuata. New pathways were created through the extraction, examination and verification of related data from the literature and the aid of external database guided by an expert-led curation process. Here we describe the curation progress that has been achieved in these databases since the first release version 1.0 in 2016, the curation flow and the curation process using the example metabolic pathway for cholesterol in plants. The current content of our databases comprises 266 pathways and 36 superpathways in SolanaCyc and 143 pathways plus 21 superpathways in NicotianaCyc, manually curated and validated specifically for the Solanaceae family and Nicotiana genus, respectively. The curated data have been propagated to the respective Nicotiana-specific databases, which resulted in the enrichment and more accurate presentation of their metabolic networks. The quality and coverage in those databases have been compared with related external databases and discussed in terms of literature support and metabolic content.

Early versus late initiation of GH replacement in adult-onset hypopituitarism.

Introduction:Adult-onset growth hormone deficiency (AGHD) is usually the last deficiency to be substituted in hypopituitarism. In children with documented GH deficiency, treatment without delay is crucial for achieving optimal effects on growth and development. In adults, it is not known whether a delay in treatment initiation influences biochemical response and the favourable physiological effects resulting from GH replacement therapy (GHRT).Methods:A total of 1085 GH-deficient adults from KIMS (Pfizer International Metabolic Database) were included, adequately replaced with all pituitary hormones except for GH at baseline. Patients were stratified by sex and age (20–50 years and ≥50 years) and subsequently divided into two groups below and above the median duration of unsubstituted AGHD for that subgroup. The median time of unsubstituted GHD for the total cohort was 2.53 years (P5 = 0.35, P95 = 24.42).Results:Beneficial effects of 4 years of GHRT were observed on lipids and quality of life in all subgroups. A decrease in waist circumference was observed only in older (>50 years) patients. There was no difference in IGF-I SDS and in GH dose required to normalize IGF-I in patients with a duration of unsubstituted AGHD above or below the median. No relevant differences were found between the groups for anthropometric measures, cardiovascular risk factors and quality of life scores.Conclusion:In contrast to GHD in children and adolescents, no difference could be established in treatment response between early or late initiation of GHRT in AGHD in terms of required GH dose, IGF-I, metabolic health and quality of life.

Human follicular fluid proteome reveals association between overweight status and oocyte maturation abnormality

BackgroundHuman follicular fluid (HFF), which is composed by essential proteins required for the follicle development, provides an important microenvironment for oocyte maturation. Recently, overweight status has been considered as a detrimental impact factor on oocyte maturation, but whether HFF proteome could provide protein markers for assessing overweight-based oocyte maturation deficiency is still unknown.MethodsTo reveal the HFF-based molecular characteristics associated with abnormal oocyte maturation, an iTRAQ-based comparative proteomic analysis was performed to investigate different HFF protein expression profiles from normal weight women and overweight status women.ResultsTwo hundred HFF proteins were quantified in our data, of which 43% have not been overlapped by two previous publications. Compared with the HFF proteins of normal weight women, 22 up-regulated HFF proteins and 21 down-regulated HFF proteins were found in the overweight status women. PANTHER database showed these altered HFF proteins participated in development, metabolism, immunity, and coagulation, and STRING database demonstrated their complicated interaction networks. The confidence of proteomic outcome was verified by Western blot analysis of WAP four-disulfide core domain protein 2 (WFDC2), lactotransferrin (LTF), prostate-specific antigen (KLK3), fibronectin (FN1), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Further, ELISA assay indicated WFDC2 might be a potentially useful candidate HFF marker for the diagnosis of oocyte maturation arrest caused by overweight status.ConclusionsOur work provided a new complementary high-confidence HFF dataset involved in oocyte maturation, and these altered HFF proteins might have clinical relevance and diagnostic and prognostic value for abnormal oocyte maturation in overweight status women.

Does Steroid Use in Transplant Patients Undergoing Bariatric Surgery Independently Impact Outcomes?

BackgroundCorticosteroids have been a mainstay of immunosuppression in patients after solid organ transplantation. Due to deleterious effects, there is a push to minimize steroid use. The impact of corticosteroid use on prior solid organ transplant patients undergoing metabolic and bariatric surgery (MBS) is unknown. The aim of this study was to determine if corticosteroid use independently impacts surgical outcomes after MBS in solid organ transplant patients. Materials and methodsA retrospective analysis was performed on patients undergoing sleeve gastrectomy and Roux-en-Y gastric bypass in the 2017 Metabolic and Bariatric Surgery Accreditation Quality and Improvement Project Participant Use File database. Patients with a history of solid organ transplantation were identified and further stratified by corticosteroid use. Univariable and multivariable regression for multiple postoperative outcomes were performed. ResultsOverall findings are summarized in visual abstract. Of 382 prior solid organ transplant patients, 42% (n = 160) were on corticosteroids. Patients on corticosteroids had significantly higher overall morbidity (16% versus 9%, P < 0.05). After multivariable analysis, corticosteroid use had a two-fold increase in overall morbidity (odds ratio 2.05, P = 0.0034) but without an increased risk for overall morbidity related to MBS (odds ratio 2.06, P = 0.061). ConclusionsSolid organ transplant patients undergoing MBS on corticosteroids have a significantly increased rate of overall morbidity (P < 0.05) but not morbidity related to bariatric surgery.

Identifying the characteristics of brain glucose metabolism using normal 18F-FDG PET database in patients with temporal lobe epilepsy

This study aimed to measure the global brain glucose metabolism of patients with temporal lobe epilepsy (TLE) using MIMneuro software based on the normal brain glucose metabolism database. In this cross-sectional study, 23 patients (11 males and 12 females, mean age 25.6 ± 10.1years) with TLE who underwent 18F-labeled fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) were enrolled. 18F-FDG PET images were then imported into MIMneuro software, which can automatically analyze the differences in regional brain glucose metabolism between patients and a normal database, and the results of different brain regions were presented by values of Z-score. In patients with TLE, 18F-FDG PET imaging showed that in addition to the presence of temporal lobe hypometabolism, there was hypometabolism in the ipsilateral hippocampus, parahippocampal gyrus, insula, amygdala, temporal operculum, and bilateral cerebellar hemisphere, while hypermetabolism was found in the contralateral temporal lobe, frontal lobe, parietal lobe, parietal lobule, angular gyrus, and precentral gyrus. There was no significant difference in brain areas between the left and the right temporal lobe seizures (P > 0.05). We found that TLE has a specific characteristic in terms of brain glucose metabolism, and the underlying mechanism needs to be further studied that may be helpful to localize seizure focus.

Trends in revisional bariatric surgery using the MBSAQIP database 2015-2017.

The third most common bariatric surgery is revisional bariatric surgery. The American College of Surgeons tracks outcomes using the Metabolic and Bariatric Surgery Accreditation Quality Initiative Program database. We used this database to examine trends in revisional bariatric surgery. To evaluate how trends in bariatric revisional surgery have changed in recent years. University Hospital, United States. The Metabolic and Bariatric Surgery Accreditation Quality Initiative Program database for 2015 to 2017 was examined for revisions of bariatric surgery. Patients who underwent revisional bariatric surgery were identified by the primary Current Procedural Terminology code, the REVCONV and PREVIOUS_SURGERY field as well as secondary Current Procedural Terminology codes. There is no exact code for sleeve gastrectomy (SG) to laparoscopic Roux-en-Y gastric bypass (LRYGB), so we used 43644 (GB)+REVCONV+PREVIOUS_SURGERY for this. For the years 2015 to 2017 there were 57,683 revisions/conversions of 528,081 patients. The number of revisions increased over the study period by 5213 cases. The most common revision was laparoscopic adjustable gastric band (LAGB) to SG with 15,433 cases and the second was LAGB to LRYGB with 10,485 cases. There were 14,715 LAGB removals. It is more difficult to track SG to LRYGB but there were 8491 unlisted cases, which may have been sleeve to bypass. LAGBs are being taken out or converted, and this group makes up the largest portion of revisions and conversions. It is difficult to track SG to LRYGB, but the number of unlisted cases continues to climb. This will likely surpass LAGB conversions with time. The Metabolic and Bariatric Surgery Accreditation Quality Initiative Program should be modified to capture revisions/conversions of SG.

Analysis of the active fraction of Iranian Naja naja oxiana snake venom on the metabolite profiles of the malaria parasite by 1HNMR in vitro.

Objective(s):Malaria is an important parasitic disease with high morbidity and mortality in tropical areas. Resistance to most antimalarial drugs has encouraged the development of new drugs including natural products. Venom is a complex mixture of active pharmaceutical ingredients. The purpose of this study was to investigate the antimalarial activity of purified fractions of Naja naja oxiana. Materials and Methods:Lyophilized venom was purified with a Sephacryl S-200 HR column and the fractions lyophilized and inhibitory concentration 50% against Plasmodium falciparum 3D7 in vitro obtained. The 4th fraction was run on a Mono Q column, and activity against P. falciparum was detected by lactate dehydrogenase assay and purity by SDS PAGE. Large scale culture of the parasite was carried out with and without the active fraction on the ring stage for 48 hr. The parasites were collected and lyophilized and analyzed by 1HNMR. Chemometrics studies were performed using MATLAB, differentiating metabolites were identified by Human Metabolic Database, and metabolic pathways by the Metaboanalyst online package. Results:The active fraction from the ion exchange column had a 50% inhibitory concentration of 0.026 µg/ml on P. falciparum in vitro (P<0.001) with molecular weight of 63 kDa by SDS-PAGE and no hemolytic activity. Metabolomics studies on the two groups with and without the fraction identified 5 differentiating metabolites and a number of related pathways.Conclusion:The metabolites were succinic acid, l-glutamic acid, pyruvic acid, cholesterol, and NAD. The changes in the Krebs cycle and metabolism pathways of nicotinamide and pyruvate were noticeable.

Pharmacodynamics of Ceftiofur Selected by Genomic and Proteomic Approaches of Streptococcus parauberis Isolated from the Flounder, Paralichthys olivaceus.

We employed an integrative strategy to present subtractive and comparative metabolic and genomic-based findings of therapeutic targets against Streptococcus parauberis. For the first time, we not only identified potential targets based on genomic and proteomic database analyses but also recommend a new antimicrobial drug for the treatment of olive flounder (Paralichthys olivaceus) infected with S. parauberis. To do that, 102 total annotated metabolic pathways of this bacterial strain were extracted from computational comparative metabolic and genomic databases. Six druggable proteins were identified from these metabolic pathways from the DrugBank database with their respective genes as mtnN, penA, pbp2, murB, murA, coaA, and fni out of 112 essential nonhomologous proteins. Among these hits, 26 transmembrane proteins and 77 cytoplasmic proteins were extracted as potential vaccines and drug targets, respectively. From the FDA DrugBank, ceftiofur was selected to prevent antibiotic resistance as it inhibited our selected identified target. Florfenicol is used for treatment of S. parauberis infection in flounder and was chosen as a comparator drug. All tested strains of fish isolates with S. parauberis were susceptible to ceftiofur and florfenicol with minimum inhibitory concentrations (MIC) of 0.0039–1 μg/mL and 0.5–8 μg/mL, IC50 of 0.001–0.5 μg/mL and 0.7–2.7 μg/mL, and minimum biofilm eradication concentrations (MBEC) of 2–256 μg/mL and 4–64 μg/mL, respectively. Similar susceptibility profiles for ceftiofur and florfenicol were found, with ceftiofur observed as an effective and potent antimicrobial drug against both planktonic and biofilm-forming strains of the fish pathogen Streptococcus parauberis, and it can be applied in the aquaculture industry. Thus, our predictive approach not only showed novel therapeutic agents but also indicated that marketed drugs should also be tested for efficacy against newly identified targets of this important fish pathogen.

Multiple Metabolic Innovations and Losses Are Associated with Major Transitions in Land Plant Evolution.

Investigating the evolution of plant biochemistry is challenging because few metabolites are preserved in fossils and because metabolic networks are difficult to experimentally characterize in diverse extant organisms. We report a comparative computational approach based on whole-genome metabolic pathway databases of eight species representative of major plant lineages, combined with homologous relationships among genes of 72 species from streptophyte algae to angiosperms. We use this genomic approach to identify metabolic gains and losses during land plant evolution. We extended our findings with additional analysis of 305 non-angiosperm plant transcriptomes. Our results revealed that genes encoding the complete biosynthetic pathway for brassinosteroid phytohormones and enzymes for brassinosteroid inactivation are present only in spermatophytes. Genes encoding only part of the biosynthesis pathway are present in ferns and lycophytes, indicating a stepwise evolutionary acquisition of this pathway. Nevertheless, brassinosteroids are ubiquitous in land plants, suggesting that brassinosteroid biosynthetic pathways differ between earlier- and later-diverging lineages. Conversely, genes for gibberellin biosynthesis and inactivation using methyltransferases are found in all land plant lineages. This suggests that bioactive gibberellins might be present in bryophytes, although they have yet to be detected experimentally. We also found that cytochrome P450 oxidases involved in cutin and suberin production are absent in genomes of non-angiosperm plants that nevertheless do contain these biopolymers. Overall, we identified significant differences in crucial metabolic processes between angiosperms and earlier-diverging land plants and resolve details of the evolutionary history of several phytohormone and structural polymer biosynthetic pathways in land plants.

MetaBridge: An Integrative Multi-Omics Tool for Metabolite-Enzyme Mapping.

MetaBridge is a web-based tool designed to facilitate the integration of metabolomics with other "omics" data types such as transcriptomics and proteomics. It uses data from the MetaCyc metabolic pathway database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to map metabolite compounds to directly interacting upstream or downstream enzymes in enzymatic reactions and metabolic pathways. The resulting list of enzymes can then be integrated with transcriptomics or proteomics data via protein-protein interaction networks to perform integrative multi-omics analyses. MetaBridge was developed to be intuitive and easy to use, requiring little to no prior computational experience. The protocols described here detail all steps involved in the use of MetaBridge, from preparing input data and performing metabolite mapping to utilizing the results to build a protein-protein interaction network. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Mapping metabolite data using MetaCyc identifiers Basic Protocol 2: Mapping metabolite data using KEGG identifiers Support Protocol 1: Converting compound names to HMDB IDs Support Protocol 2: Submitting mapped genes produced by MetaBridge for protein-protein interaction (PPI) network construction.

Epileptogenic zone localization using a new automatic quantitative analysis based on normal brain glucose metabolism database

Objectives To assess the clinical value of voxel-based automatic quantitative analysis using a normal brain glucose metabolism database in the preoperative localization of focal intractable temporal lobe epilepsy patients. Methods Patients with refractory temporal lobe epilepsy who underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging were retrospectively enrolled from January to June 2017. Visual analysis was performed by two nuclear medicine radiologists, and the automatic quantitative analysis was carried out using MIMneuro software based the age- and gender-stratified normal brain glucose metabolism database. Setting postoperative outcomes as reference, the consistency between visual analysis and automatic quantitative analysis was tested by Cohen’s kappa coefficient, and differences in localization of epileptic foci of the two methods were compared by Chi-square test. Results A total of 32 patients intractable temporal lobe epilepsy were included in this study. There was a moderate agreement between the automatic quantitative analysis based on MIMneuro software and visual analysis (kappa coefficient = 0.472, p = 0.002). In terms of the efficiency of focus localization, the voxel-based automatic quantitative analysis was higher than that of visual analysis (Chi-square value = 6.969, p = 0.008). Conclusions The voxel-based automatic quantitative analysis combined with normal brain glucose metabolism database had a certain clinical application value for detection temporal lobe epilepsy.

Deep Learning Based Drug Metabolites Prediction.

Drug metabolism research plays a key role in the discovery and development of drugs. Based on the discovery of drug metabolites, new chemical entities can be identified and potential safety hazards caused by reactive or toxic metabolites can be minimized. Nowadays, computational methods are usually complementary tools for experiments. However, current metabolites prediction methods tend to have high false positive rates with low accuracy and are usually only used for specific enzyme systems. In order to overcome this difficulty, a method was developed in this paper by first establishing a database with broad coverage of SMARTS-coded metabolic reaction rule, and then extracting the molecular fingerprints of compounds to construct a classification model based on deep learning algorithms. The metabolic reaction rule database we built can supplement chemically reasonable negative reaction examples. Based on deep learning algorithms, the model could determine which reaction types are more likely to occur than the others. In the test set, our method can achieve the accuracy of 70% (Top-10), which is significantly higher than that of random guess and the rule-based method SyGMa. The results demonstrated that our method has a certain predictive ability and application value.

Attending Specialization and 30-Day Outcomes Following Laparoscopic Bariatric Surgery: an Analysis of the ACS-MBSAQIP Database.

Surgeon and hospital volume are factors that have been shown to impact outcomes following bariatric surgery. Nevertheless, there is a paucity of literature investigating surgeon training on bariatric surgery outcomes. The purpose of our study was to determine if bariatric specialty training leads to improved short-term outcomes following laparoscopic bariatric surgery using the American College of Surgeons Metabolic and Bariatric Surgery Accreditation Quality Improvement Program (ACS-MBSAQIP) database. All patients undergoing first-time, elective, laparoscopic bariatric surgery from 2015 to 2016 were identified within the ACS-MBSAQIP database. Patients were divided into two groups based on the type of bariatric procedure performed and the surgeon performing the procedure. Thirty-day outcomes were compared between the groups using multivariable logistic regression analysis. A total of 140,340 patients met inclusion criteria. Higher risk patients with more associated comorbidities underwent bariatric surgery by a metabolic and bariatric surgeon. After controlling for these differences, patients who underwent Roux-en-Y gastric bypass (RYGB) had similar 30-day irrespective of the surgeon performing the procedure while patients who underwent sleeve gastrectomy (SG) by a metabolic and bariatric surgeon (MBS) had improved 30-day outcomes. Surgeon type is associated with 30-day morbidity and mortality outcomes for SG but not for RYGB. These differences in 30-day morbidity and mortality outcomes may be facilitated by institutional factors, surgeon experience, and participation in bariatric surgery accredited centers. Standardization of the perioperative process for both surgeons and institutions may improve 30-day morbidity and mortality outcomes for all patients who undergo laparoscopic bariatric surgery.

Placental transporter-mediated drug interactions and offspring congenital anomalies.

AimsP‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP) are efflux transporters expressed in the placenta, limiting their substrates from reaching the foetus. Our aim was to investigate if concomitant prenatal exposure to several substrates or inhibitors of these transporters increases the risk of congenital anomalies.MethodsThe national Drugs and Pregnancy database, years 1996–2014, was utilized in this population‐based birth cohort study. In the database, the Medical Birth Register, the Register on Induced Abortions, the Malformation register and the Register on Reimbursed Drug Purchases have been linked. The University of Washington Metabolism and Transport Drug Interaction Database was used to identify substrates and inhibitors of P‐gp and BCRP. We included singleton pregnancies ending in birth or elective termination of pregnancy due to foetal anomaly. Known teratogens were excluded. We identified women exposed 1 month before pregnancy or during the first trimester to P‐gp/BCRP polytherapy (n = 21 186); P‐gp/breast cancer resistance protein monotherapy (n = 97 906); non‐P‐gp/BCRP polytherapy (n = 78 636); and unexposed (n = 728 870). We investigated the association between the exposure groups and major congenital anomalies using logistic regression adjusting for several confounders.ResultsThe prevalence of congenital anomalies was higher in the P‐gp/BCRP polytherapy group (5.5%) compared to the P‐gp/BCRP monotherapy (4.7%, OR 1.13; 95% CI 1.05–1.21), the non‐P‐gp/BCRP polytherapy (4.9%, OR 1.14; 95% CI 1.06–1.22), and to the unexposed groups (4.2%, OR 1.23; 95% CI 1.15–1.31).ConclusionThe results suggest a role of placental transporter‐mediated drug interactions in teratogenesis.

A preliminary study of resting brain metabolism in treatment-resistant depression before and after treatment with olanzapine-fluoxetine combination.

Treatment-resistant depression (TRD) occurs in many patients and causes high morbidity and mortality. Because TRD subjects are particularly difficult to study especially longitudinally, biological data remain very limited. In a preliminary study to judge feasibility and power, 25 TRD patients were referred from specialty psychiatric practices. All were severely and chronically depressed and mostly had comorbid psychiatric disorders as is typical in TRD. Nine patients were able to complete all required components of the protocol that included diagnostic interview; rating scales; clinical magnetic resonance imaging; medication washout; treatment with maximally tolerated olanzapine-fluoxetine combination for 8 weeks; and pre- and post-treatment fluorodeoxyglucose positron emission tomography. This drug combination is an accepted standard of treatment for TRD. Dropouts arose from worsening depression, insomnia, and anxiety. One patient remitted; three responded. A priori regions of interest included the amygdala and subgenual cingulate cortex (sgACC; Brodmann area BA25). Responders showed decreased metabolism with treatment in the right amygdala that correlated with clinical response; no significant changes in BA25; better response to treatment the higher the baseline BA25 metabolism; and decreased right ventromedial prefrontal metabolism (VMPFC; broader than BA25) with treatment which did not correlate with depression scores. The baseline metabolism of all individuals showed heterogeneous patterns when compared to a normative metabolic database. Although preliminary given the sample size, this study highlights several issues important for future work: marked dropout rate in this study design; need for large sample size for adequate power; baseline metabolic heterogeneity of TRD requiring careful subject characterization for future studies of interventions; relationship of amygdala activity decreases with response; and the relationship between baseline sgACC and VMPFC activity with response. Successful treatment of TRD with olanzapine-fluoxetine combination shows changes in cerebral metabolism like those seen in treatment-responsive major depression.

Improving the organization and interactivity of metabolic pathfinding with precomputed pathways

BackgroundThe rapid growth of available knowledge on metabolic processes across thousands of species continues to expand the possibilities of producing chemicals by combining pathways found in different species. Several computational search algorithms have been developed for automating the identification of possible heterologous pathways; however, these searches may return thousands of pathway results. Although the large number of results are in part due to the large number of possible compounds and reactions, a subset of core reaction modules is repeatedly observed in pathway results across multiple searches, suggesting that some subpaths between common compounds were more consistently explored than others.To reduce the resources spent on searching the same metabolic space, a new meta-algorithm for metabolic pathfinding, Hub Pathway search with Atom Tracking (HPAT), was developed to take advantage of a precomputed network of subpath modules. To investigate the efficacy of this method, we created a table describing a network of common hub metabolites and how they are biochemically connected and only offloaded searches to and from this hub network onto an interactive webserver capable of visualizing the resulting pathways.ResultsA test set of nineteen known pathways taken from literature and metabolic databases were used to evaluate if HPAT was capable of identifying known pathways. HPAT found the exact pathway for eleven of the nineteen test cases using a diverse set of precomputed subpaths, whereas a comparable pathfinding search algorithm that does not use precomputed subpaths found only seven of the nineteen test cases. The capability of HPAT to find novel pathways was demonstrated by its ability to identify novel 3-hydroxypropanoate (3-HP) synthesis pathways. As for pathway visualization, the new interactive pathway filters enable a reduction of the number of displayed pathways from hundreds down to less than ten pathways in several test cases, illustrating their utility in reducing the amount of presented information while retaining pathways of interest.ConclusionsThis work presents the first step in incorporating a precomputed subpath network into metabolic pathfinding and demonstrates how this leads to a concise, interactive visualization of pathway results. The modular nature of metabolic pathways is exploited to facilitate efficient discovery of alternate pathways.

Change in baseline characteristics over 20 years of adults with growth hormone (GH) deficiency on GH replacement therapy.

Clinical observations over time of adults with growth hormone (GH) deficiency (GHD) have indicated a shift in patient characteristics at diagnosis. The objective of this study was to compare baseline characteristics of patients diagnosed with adult-onset GHD naive to GH replacement during three study periods (1994-1999 (P1), 2000-2004 (P2), and 2005-2012 (P3)) using the KIMS (Pfizer's International Metabolic) database. Data were retrieved for a total of 6069 patients with adult-onset GHD from six countries (Belgium, Germany, Netherlands, Spain, Sweden, and UK): P1 (n = 1705), P2 (n = 2397), and P3 (n = 1967). The proportions of patients with pituitary/hypothalamic tumors and patients with multiple pituitary hormone deficiencies decreased per entry year period, while the proportions with hypertension and diabetes increased. The lag time from diagnosis of pituitary disease to start of GH treatment decreased by 2.9 years over the entry year periods. IGF-1 increased by 0.1 standard deviation score per entry year period. Maximum GH following various stimulation tests, BMI, and waist circumference increased. The use of radiotherapy, glucocorticoid replacement doses, and the proportion of women >50 years on estrogen replacement therapy decreased. The effects of 1 year of GH replacement were similar over the entry year periods despite changes in the patients' baseline characteristics. An expected increase in fasting blood glucose was seen after 1 year of GH treatment. The degree of confirmed GHD became less pronounced and more patients with co-morbidities and diabetes were considered for GH replacement therapy, possibly reflecting increased knowledge and confidence in GH therapy gained with time.

NcRNA2MetS: a manually curated database for non-coding RNAs associated with metabolic syndrome.

Metabolic syndrome is a cluster of the most dangerous heart attack risk factors (diabetes and raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure), and has become a major global threat to human health. A number of studies have demonstrated that hundreds of non-coding RNAs, including miRNAs and lncRNAs, are involved in metabolic syndrome-related diseases such as obesity, type 2 diabetes mellitus, hypertension, etc. However, these research results are distributed in a large number of literature, which is not conducive to analysis and use. There is an urgent need to integrate these relationship data between metabolic syndrome and non-coding RNA into a specialized database. To address this need, we developed a metabolic syndrome-associated non-coding RNA database (ncRNA2MetS) to curate the associations between metabolic syndrome and non-coding RNA. Currently, ncRNA2MetS contains 1,068 associations between five metabolic syndrome traits and 627 non-coding RNAs (543 miRNAs and 84 lncRNAs) in four species. Each record in ncRNA2MetS database represents a pair of disease-miRNA (lncRNA) association consisting of non-coding RNA category, miRNA (lncRNA) name, name of metabolic syndrome trait, expressive patterns of non-coding RNA, method for validation, specie involved, a brief introduction to the association, the article referenced, etc. We also developed a user-friendly website so that users can easily access and download all data. In short, ncRNA2MetS is a complete and high-quality data resource for exploring the role of non-coding RNA in the pathogenesis of metabolic syndrome and seeking new treatment options. The website is freely available at http://www.biomed-bigdata.com:50020/index.html

Concurrent bariatric surgery and paraesophageal hernia repair: an analysis of the Metabolic and Bariatric Surgery Association Quality Improvement Program (MBSAQIP) database

BackgroundParaesophageal hernias (PEH) are common among patients with obesity. Most patients with severe obesity and a PEH will have the PEH repaired at the time of bariatric surgery. However, it is unclear whether there is increased risk when repairing a PEH during bariatric surgery. ObjectivesTo examine short-term outcomes of patients undergoing bariatric surgery with concurrent PEH repair versus bariatric surgery alone. SettingAccredited bariatric centers across the United States and Canada. MethodsPatients who underwent bariatric surgery with concurrent PEH repair were identified from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program data registry. Using a propensity-score matching algorithm, these patients were matched with a cohort who underwent bariatric surgery only, controlling for age, sex, and other co-morbidities. Overall, 30-day incidence of major complications was the primary outcome. Secondary outcomes included mortality, length of operation, reoperations, and readmissions. ResultsThe Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database identified 222,320 bariatric procedures without PEH and 42,732 procedures with concurrent PEH repair. With one-to-one propensity score matching, 42,379 pairs were selected. Background characteristics, including age, sex, preoperative body mass index, and preoperative co-morbidities, did not differ statistically between matched cohorts. There was no statistically significant difference in 30-day major complications (3.5% versus 3.4%, P = .317). ConclusionsOur analysis indicates that the incidence of major complications for bariatric surgery with concurrent PEH repair is similar to bariatric surgery alone. Overall, this study demonstrates the safety of concurrent bariatric surgery and PEH repair.

The effect of bougie size and distance from the pylorus on dehydration after laparoscopic sleeve gastrectomy: an analysis of the ACS-MBSAQIP database

BackgroundDehydration is the most common cause of readmission after laparoscopic sleeve gastrectomy (SG). Bougie size and distance from the pylorus, both of which have been associated with rates of dehydration postoperatively, varies by surgeon and across institutions. ObjectivesTo determine if there is an association between bougie size or distance from the pylorus on the rate of dehydration after laparoscopic SG. SettingAmerican College of Surgeons Metabolic and Bariatric Surgery Accreditation Quality Improvement Program database. MethodsAll patients undergoing first-time, elective laparoscopic SG from 2015–2016 were identified. The association of bougie size and distance from the pylorus on the rate of dehydration within the first 30 days postoperatively was investigated. ResultsThe inclusion criteria were met by 170,751 patients. The most commonly used bougie size was 36 Fr and the most common distance from the pylorus at which the gastric sleeve was started was 5 cm. Patients were divided into 4 groups based on bougie size and distance from the pylorus (Group 1: bougie size <36 Fr, pylorus distance <4 cm; Group 2: bougie size ≥36 Fr, pylorus distance <4 cm; Group 3: bougie size ≥36 Fr, pylorus distance ≥4 cm; and Group 4: bougie size <36 Fr, pylorus distance ≥4 cm). Patients in Group 4 were significantly less likely than any other group to experience dehydration-related complications. ConclusionBoth distance from the pylorus and bougie size are significantly associated with dehydration-related complications after SG. Consideration should be made for standardizing these technical aspects of SG to help reduce the rate of postoperative dehydration and hospital readmission.