Associations of Preterm Birth with Dental and Gastrointestinal Diseases: Machine Learning Analysis Using National Health Insurance Data.

BACKGROUND: This study uses machine learning with large-scale population data to assess the associations of preterm birth (PTB) with dental and gastrointestinal diseases. METHODS: Population-based retrospective cohort data came from Korea National Health Insurance claims for 124,606 primiparous women aged 25-40 and delivered in 2017. The 186 independent variables included demographic/socioeconomic determinants, disease information, and medication history. Machine learning analysis was used to establish the prediction model of PTB. Random forest variable importance was used for identifying major determinants of PTB and testing its associations with dental and gastrointestinal diseases, medication history, and socioeconomic status. RESULTS: The random forest with oversampling data registered an accuracy of 84.03, and the areas under the receiver-operating-characteristic curves with the range of 84.03-84.04. Based on random forest variable importance with oversampling data, PTB has strong associations with socioeconomic status (0.284), age (0.214), year 2014 gastroesophageal reflux disease (GERD) (0.026), year 2015 GERD (0.026), year 2013 GERD (0.024), progesterone (0.024), year 2012 GERD (0.023), year 2011 GERD (0.021), tricyclic antidepressant (0.020) and year 2016 infertility (0.019). For example, the accuracy of the model will decrease by 28.4%, 2.6%, or 1.9% if the values of socioeconomic status, year 2014 GERD, or year 2016 infertility are randomly permutated (or shuffled). CONCLUSION: By using machine learning, we established a valid prediction model for PTB. PTB has strong associations with GERD and infertility. Pregnant women need close surveillance for gastrointestinal and obstetric risks at the same time.

Bovine colostrum derived-exosomes prevent dextran sulfate sodium-induced intestinal colitis via suppression of inflammation and oxidative stress.

Despite the rise in the global burden of inflammatory bowel disease, there is a lack of safe and effective therapies that can meet the needs of clinical patients. In this study, we investigated the beneficial effects of bovine milk, especially colostrum-derived exosomes (Col-exo) in a murine model of ulcerative colitis induced by dextran sodium sulfate (DSS). Col-exo activated the proliferation of colonic epithelial cells and macrophages, and created an environment to relieve inflammation by effectively removing reactive oxygen species and regulating the expression of immune cytokines. Besides, Col-exo could pass through the gastrointestinal tract intact and efficiently deliver bioactive cargoes to the stomach, small intestine, and colon. Our results showed that oral gavage of Col-exo can alleviate colitis symptoms including weight loss, gastrointestinal bleeding, and chronic diarrhea by modulating intestinal inflammatory immune responses. Overall, bovine colostrum-derived exosomes with excellent structural and functional stability may offer great potential as natural therapeutics for the recovery of colitis.

Association of Preterm Birth with Inflammatory Bowel Disease and Salivary Gland Disease: Machine Learning Analysis Using National Health Insurance Data.

This study employs machine learning and population data for testing the associations of preterm birth with inflammatory bowel disease (IBD), salivary gland disease, socioeconomic status and medication history, including proton pump inhibitors. The source of population-based retrospective cohort data was the Korea National Health Insurance Service claims data for all women aged 25-40 years and who experience their first childbirths as singleton pregnancy during 2015 to 2017 (402,092 women). These participants were divided into the Ulcerative Colitis (UC) Group (1782 women), the Crohn Group (1954 women) and the Non-IBD Group (398,219 women). For each group, the dependent variable was preterm birth during 2015-2017, and 51 independent variables were included. Random forest variable importance was employed for investigating the main factors of preterm birth and testing its associations with salivary gland disease, socioeconomic status and medication history for each group. The proportion of preterm birth was higher for the UC Group and the Non-IBD Group than for the Crohn Group: 7.86%, 7.17% vs. 6.76%. Based on random forest variable importance, salivary gland disease was a top 10 determinant for the prediction of preterm birth for the UC Group, but this was not the case for the Crohn Group or the Non-IBD Group. The top 5 variables of preterm birth for the UC Group during 2015-2017 were socioeconomic status (8.58), age (8.00), proton pump inhibitors (2.35), progesterone (2.13) and salivary gland disease in 2014 (1.72). In conclusion, preterm birth has strong associations with ulcerative colitis, salivary gland disease, socioeconomic status and medication history including proton pump inhibitors.

The Effect of Omega-3 Enriched Oral Nutrition Supplement on Nutritional Indices and Quality of Life in Gastrointestinal Cancer Patients: A Randomized Clinical Trial.

OBJECTIVE: Gastrointestinal (GI) cancer patients often experience severe malnutrition during cancer therapies due to gastrointestinal dysfunctions including poor digestion and absorption as well as tumor-associated anorexia. In this study, we performed a randomized clinical trial to determine the efficacy of oral nutrition supplement (ONS) enriched with omega-3 fatty acids on nutritional status, quality of life (QOL), and pro-inflammatory indices. METHODS: Patients diagnosed with GI cancers were recruited and screened for eligibility. A total of 58 patients were randomly allocated to either the control group (n=27) or the experimental group (n=31). The intervention group received 200 ml ONS twice a day while the control group received routine care. Anthropometrics, Patient-Generated Subjective Global Assessment (PG-SGA) score, QOL score and nutrient intake data were collected at baseline, week 4 and week 8. Blood was drawn for biochemical assessments. Nine patients from each group dropped out of the study Forty patients (18 control patients and 22 intervention patients) completed the study. RESULTS: This study showed that ONS intervention improved PG-SGA scores in the intervention group (p<0.01). Scores of physical functioning score and role functioning were declined only in the control group and the difference between week 8 and baseline for role functioning was significant (p<0.001). Fatigue score was steadily decreased in the experiment group, and the differences between week 8 and baseline was significant between two groups (p<0.02). However, no statistically significant improvement in biochemical markers of nutritional status and pro-inflammatory cytokine concentrations were found. These results suggests that ONS intervention for 8 weeks improves PG-SGA scores and QOL scores in patients undergoing cancer therapy.

Association of preterm birth with medications: machine learning analysis using national health insurance data.

PURPOSE: To use machine learning and population data for testing the associations of preterm birth with socioeconomic status, gastroesophageal reflux disease (GERD) and medication history including proton pump inhibitors, sleeping pills and antidepressants. METHODS: Population-based retrospective cohort data came from Korea National Health Insurance Service claims data for all women who aged 25-40 years and gave births for the first time as singleton pregnancy during 2015-2017 (405,586 women). The dependent variable was preterm birth during 2015-2017 and 65 independent variables were included (demographic/socioeconomic determinants, disease information, medication history, obstetric information). Random forest variable importance (outcome measure) was used for identifying major determinants of preterm birth and testing its associations with socioeconomic status, GERD and medication history including proton pump inhibitors, sleeping pills and antidepressants. RESULTS: Based on random forest variable importance, major determinants of preterm birth during 2015-2017 were socioeconomic status (645.34), age (556.86), proton pump inhibitors (107.61), GERD for the years 2014, 2012 and 2013 (106.78, 105.87 and 104.96), sleeping pills (97.23), GERD for the years 2010, 2011 and 2009 (95.56, 94.84 and 93.81), and antidepressants (90.13). CONCLUSION: Preterm birth has strong associations with low socioeconomic status, GERD and medication history such as proton pump inhibitors, sleeping pills and antidepressants. For preventing preterm birth, appropriate medication would be needed alongside preventive measures for GERD and the promotion of socioeconomic status for pregnant women.

Reproductive trade-offs maintain bract color polymorphism in Scarlet Indian paintbrush (Castilleja coccinea).

Populations of scarlet Indian paintbrush (Castilleja coccinea) in the Midwestern United States exhibit a bract color polymorphism, with each population having predominantly yellow or scarlet bracts. We investigated a possible mechanism for this maintenance of bract color polymorphism in C. coccinea by conducting hand-pollination experiments in two nearby populations, one predominantly yellow and one predominantly scarlet. The hand-pollination treatments were either self-pollination or cross pollination using pollen from within and between populations. Both color morphs were used as pollen donors for the within and between crosses. We found that both color morphs of C. coccinea were self-compatible. When the scarlet morph was the maternal plant it had higher seed set. When pollinators were excluded, the yellow morph outperformed the scarlet morph in fruit set and seed set. The apparent trade-offs between a higher reproductive output in the scarlet morph and a reproductive assurance advantage in the yellow morph may explain the maintenance of the polymorphism in C. coccinea. While many previous studies have provided evidence for pollinator preference playing a role in floral color polymorphism, the results of the current study indicate that reproductive assurance, which would be important for fluctuations in pollinator abundance or colonizing new areas, may act as a selective agent to maintain such polymorphisms.

Increased heat shock protein 70 expression attenuates pancreatic fibrosis induced by dibutyltin dichloride.

OBJECTIVES: Heat shock protein (HSP) 70 performs a chaperoning function and protects cells against injury. Although the effect of HSPs against acute inflammatory change has been proven, the relationship between HSP70 and chronic pancreatitis remains unclear. This study aimed to investigate the protective effect of increased HSP70 expression induced by thermal stress against pancreatic fibrosis in experimental chronic pancreatitis. MATERIALS AND METHODS: Two experiments to evaluate pancreatic HSP70 expression induced by thermal stress and determine the effect of increased HSP70 expression against pancreatic fibrosis were performed. To investigate HSP70 expression, rats were immersed in a warm bath and sequentially killed, and pancreatic HSP70 expression was measured. To study the effect of increased HSP70 expression, pancreatic fibrosis was induced by intravenous injection of dibutyltin dichloride (DBTC) and analyzed under repeated thermal stress. The severity of pancreatic fibrosis was measured. RESULTS: Thermal stress significantly increased HSP70 expression in the pancreas. HSP70 expression peaked at 6-12 h after warm bathing, and the increased HSP70 expression was associated with the attenuation of pancreatic fibrosis. Although pancreatic fibrosis was induced by DBTC injection, HSP70 expression induced by repeated thermal stress diminished the severity of atrophy and fibrosis. On western blot analysis, collagen type 1 expression was diminished in the increased HSP70 expression group, but not α-smooth muscle actin expression. CONCLUSIONS: Thermal stress could increase pancreatic HSP70 expression, and induced HSP70 expression showed a protective effect against pancreatic fibrosis. Modulation of HSP70 expression could be a potential therapeutic target in the treatment of chronic pancreatitis.

Selenium Administration Attenuates 5-Flurouracil-Induced Intestinal Mucositis.

Chemotherapy-induced mucositis is mediated by the release of proinflammatory cytokines and reactive oxygen species. Selenium has several metabolic functions, including the protection of membrane lipids and macromolecules against oxidative damage. However, to date, there is little evidence on the effect of trace elements on intestinal mucositis after chemotherapy. This study investigated the protective effect of selenium against chemotherapy-induced mucositis in rats. Twenty-four 9-wk-old female Wistar rats were randomized to 4 groups: control, selenium, 5-fluorouracil (5-FU), and 5-FU plus selenium. Mucositis was induced by a single dose of 5-FU (400 mg/kg BW) via intraperitoneal injection, and selenium was administered by a single intraperitoneal dose of sodium selenite (0.2 mg/kg BW). Diarrhea and weight loss after 5-FU administration were attenuated by selenium treatment. The mean villus height in the 5-FU plus selenium group was significantly taller than rats administered with 5-FU alone, but not significantly different compared to the control group. Interleukin (IL)-1ß and tumor necrosis factor (TNF)-α mRNA expression were significantly lower in the 5-FU plus selenium group than in the 5-FU only group (IL-1ß, P < 0.01; TNF-α, P < 0.05). These findings indicate that selenium protects the mucosa during chemotherapy via its anti-inflammatory effects and its suppression of cytotoxic cytokine production.

Polyethylene glycol plus ascorbic acid for bowel preparation in chronic kidney disease.

The safety of polyethylene glycol plus ascorbic acid has not been fully investigated in patients with renal insufficiency. High-dose ascorbic acid could induce hyperoxaluria, thereby causing tubule-interstitial nephritis and renal failure. This study aims to evaluate the safety and efficacy of polyethylene glycol plus ascorbic acid in patients with chronic kidney disease.We retrospectively reviewed prospectively collected data on colonoscopy in patients with impaired renal function. Patients were divided into 2 groups: 2 L polyethylene glycol plus ascorbic acid (n = 61) and 4 L polyethylene glycol (n = 80). The safety of the 2 groups was compared by assessing the differences in laboratory findings before and after bowel cleansing.The laboratory findings were not significantly different before and after the administration of 2 L polyethylene glycol plus ascorbic acid or 4 L polyethylene glycol. In both groups, the estimated glomerular filtration rate was not influenced by the administration of the bowel-cleansing agent. Patients' reports on tolerance and acceptability were better in the 2 L polyethylene glycol plus ascorbic acid group than in the 4 L polyethylene glycol group.The 2 L polyethylene glycol plus ascorbic acid solution is a safe choice for bowel preparation before colonoscopy in patients with impaired renal function.

Selective inhibition of JAK2/STAT1 signaling and iNOS expression mediates the anti-inflammatory effects of coniferyl aldehyde.

Urgent needs still exist for selective control of excessive inflammation. Despite the therapeutic potential of natural compounds against inflammation-associated chronic conditions, lack of specific molecular targets renders these bioactive compounds difficult for further development. Here we examined the bioactivity of coniferyl aldehyde (CA), a natural phenolic compound found in several dietary substances and medicinal plants, elucidating its efficacy both in vivo and in vitro with underlying molecular mechanisms. IFN-γ/TNF-α-stimulated human keratinocytes and lipopolysaccharide (LPS)-stimulated murine macrophages were used to examine the effect of CA in vitro and to elucidate the underlying mechanisms. In vivo models of phorbol 12-myristate 13-acetate (TPA)-induced ear edema and carrageenan (CRG)-induced paw edema were employed to investigate the topical and systemic anti-inflammatory effects of CA, respectively. CA significantly reduced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated macrophages. While nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPKs) pathways, the representative cellular pathways for iNOS induction, were not affected by CA, phosphorylation of Janus kinase 2 (JAK2) and signal Transducers and Activators of Transcription 1 (STAT1) and subsequent nuclear translocation of p-STAT1 were significantly decreased by CA. The effect of CA on JAK2-STAT1-iNOS axis was also observed in human keratinocytes stimulated with IFN-γ/TNF-α. Topical application of CA to mice produced significant protection against TPA-induced ear edema along with suppressed epidermal hyperproliferation and leucocyte infiltration. Systemic administration of CA significantly reduced CRG-induced paw edema in rats, where CRG-induced iNOS expression and STAT1 phosphorylation were decreased by CA. In summary, CA has significant anti-inflammatory properties both in vitro and in vivo, mediated by significant selective inhibition of JAK2-STAT1-iNOS signaling. CA is an attractive novel candidate for treating inflammatory diseases associated with excessive production of NO.

Potent Anti-inflammatory and Analgesic Actions of the Chloroform Extract of Dendropanax morbifera Mediated by the Nrf2/HO-1 Pathway.

Dendropanax morbifera LEVEILLE (DP) has been used in traditional Korean medicines to treat a variety of inflammatory diseases. Although the in vitro anti-inflammatory potential of this plant is understood, its in vivo efficacy and underlying molecular mechanism of anti-inflammatory effects are largely unknown. We elucidated the anti-inflammatory and analgesic activities and the underlying molecular mechanisms of DP using in vitro and in vivo models. Lipopolysaccharide (LPS)-stimulated murine macrophages were used to analyze the in vitro anti-inflammatory potential of DP extract and to elucidate the underlying mechanisms. In vivo animal models of phorbol 12-myristate 13-acetate (TPA)-induced ear edema and acetic acid-induced writhing response tests were used to analyze the in vivo anti-inflammatory effects and anti-nociceptive effects of DP extract, respectively. Methanolic extract of DP (DPME) significantly inhibited the release of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-activated macrophages. Among the five sub-fractions, the chloroform fraction (DP-C) showed the most potent suppressive effects against pro-inflammatory mediators and cytokines in LPS-stimulated macrophages. These effects were attributed to inhibition of nuclear factor-κB (NF-κB) nuclear translocation and c-Jun N terminal kinase (JNK) 1/2 phosphorylation and to activation of NF-E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling. DP-C exhibited strong protective in vivo effects in TPA-induced ear edema mouse model and acetic acid-induced writhing response test. Our data suggest that DP-C has potent anti-inflammatory and analgesic activities and may be a promising treatment against a variety of inflammatory diseases.

Protective activity of Dendropanax morbifera against cisplatin-induced acute kidney injury.

BACKGROUND/AIMS: Drug-induced acute kidney injury (AKI) has been a severe threat to hospitalized patients, raising the urgent needs to develop strategies to reduce AKI. We investigated the protective activity of Dendropanax morbifera (DP), a medicinal plant which has been widely used to treat infectious and pain diseases, on acute kidney injury (AKI) using cisplatin-induced nephropathic models. METHODS: Both in vitro renal tubular cells (NRK-52E) and in vivo rat models were used to demonstrate the nephroprotective effect of DP. RESULTS: Methanolic extract from DP significantly reduced cisplatin-induced toxicity in renal tubular cells. Through successive liquid extraction, the extract of DP was separated into n-hexane, CHCl3, EtOAc, n-BuOH, and H2O fractions. Among these, the CHCl3 fraction (DPCF) was found to be most potent. The protective activity of DPCF was found to be mediated through anti-oxidant, mitochondrial protective, and anti-apoptotic activities. In in vivo rat models of AKI, treatment with DPCF significantly reversed the cisplatin-induced increase in blood urea nitrogen and serum creatinine and histopathologic damage, recovered the level of anti-oxidant enzymes, and inhibited renal apoptosis. CONCLUSION: We demonstrated that DP extracts decreased cisplatin-induced renal toxicity, indicating its potential to ameliorate drug-associated acute kidney damage.

A novel non-agonist peroxisome proliferator-activated receptor γ (PPARγ) ligand UHC1 blocks PPARγ phosphorylation by cyclin-dependent kinase 5 (CDK5) and improves insulin sensitivity.

Thiazolidinedione class of anti-diabetic drugs which are known as peroxisome proliferator-activated receptor γ (PPARγ) ligands have been used to treat metabolic disorders, but thiazolidinediones can also cause several severe side effects, including congestive heart failure, fluid retention, and weight gain. In this study, we describe a novel synthetic PPARγ ligand UNIST HYUNDAI Compound 1 (UHC1) that binds tightly to PPARγ without the classical agonism and which blocks cyclin-dependent kinase 5 (CDK5)-mediated PPARγ phosphorylation. We modified the non-agonist PPARγ ligand SR1664 chemically to improve its solubility and then developed a novel PPARγ ligand, UHC1. According to our docking simulation, UHC1 occupied the ligand-binding site of PPARγ with a higher docking score than SR1664. In addition, UHC1 more potently blocked CDK5-mediated PPARγ phosphorylation at Ser-273. Surprisingly, UHC1 treatment effectively ameliorated the inflammatory response both in vitro and in high-fat diet-fed mice. Furthermore, UHC1 treatment dramatically improved insulin sensitivity in high-fat diet-fed mice without causing fluid retention and weight gain. Taken together, compared with SR1664, UHC1 exhibited greater beneficial effects on glucose and lipid metabolism by blocking CDK5-mediated PPARγ phosphorylation, and these data indicate that UHC1 could be a novel therapeutic agent for use in type 2 diabetes and related metabolic disorders.

Coffee enema for preparation for small bowel video capsule endoscopy: a pilot study.

Coffee enemas are believed to cause dilatation of bile ducts and excretion of bile through the colon wall. Proponents of coffee enemas claim that the cafestol palmitate in coffee enhances the activity of glutathione S-transferase, an enzyme that stimulates bile excretion. During video capsule endoscopy (VCE), excreted bile is one of the causes of poor preparation of the small bowel. This study aimed to evaluate the feasibility and effect of coffee enema for preparation of the small bowel during VCE. In this pilot study, 17 of 34 patients were assigned to the coffee enema plus polyethylene glycol (PEG) 2 L ingestion group, whereas the 17 remaining control patients received 2 L of PEG only. The quality of bowel preparation was evaluated in the two patient groups. Bowel preparations in the proximal segments of small bowel were not differ between two groups. In the mid and distal segments of the small intestine, bowel preparations tend to be better in patients who received coffee enemas plus PEG than in patients who received PEG only. The coffee enema group did not experience any complications or side effects. Coffee enemas may be a feasible option, and there were no clinically significant adverse events related to coffee enemas. More prospective randomized studies are warranted to improve small bowel preparation for VCE.

Bacterial yield from quantitative cultures of bronchoalveolar lavage fluid in patients with pneumonia on antimicrobial therapy.

BACKGROUND/AIMS: Early diagnosis and appropriate antimicrobial choice are crucial when managing pneumonia patients, and quantitative culture of bronchoalveolar lavage (BAL) fluid is considered a useful method for identifying pneumonia pathogens. We evaluated the quantitative yield of BAL fluid bacterial cultures in patients being treated with antimicrobials and attempted to identify factors predictive of positive BAL cultures. METHODS: Patients over 18 years old and whose BAL fluid was subjected to quantitative culture to identify the organism causative of pneumonia between January 1, 2005, and December 31, 2009, were included. We reviewed the results of BAL fluid bacterial cultures and the clinical records, laboratory tests, and radiographic findings of the patients. RESULTS: BAL was performed on 340 patients with pneumonia. A positive BAL culture, defined as isolation of more than 10(4) colony forming units/mL bacteria, was documented in 18 (5.29%) patients. Of these, 9 bacteria isolated from 10 patients were classified as probable pathogens. The most frequently isolated bacteria were methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa. No independent predictive factor for positive BAL cultures was identified. CONCLUSIONS: The yield of quantitative BAL fluid bacterial culture in patients already on antimicrobials was low. Clinicians should be cautious when performing a BAL culture in patients with pneumonia who are already on antimicrobials.

Usefulness of warm water and oil assistance in colonoscopy by trainees.

BACKGROUND AND STUDY AIMS: Success rate of cecal intubation, endoscopist's difficulty, and procedure-related patient pain are still problems for beginners performing colonoscopy. New methods to aid colonoscopic insertion such as warm water instillation and oil lubrication have been proposed. The aim of this study is to evaluate the feasibility of using warm water or oil in colonoscopy. METHODS: Colonoscopy was performed in 117 unsedated patients by three endoscopists-in-training. Patients were randomly allocated to three groups, using a conventional method with administration of antispasmodics, warm water instillation, and oil lubrication, respectively. Success rate of total intubation within time limit (15 min), cecal intubation time, degree of endoscopist's difficulty, and level of patient discomfort were compared among the three groups. RESULTS: Cecal intubation time was shorter in the warm water group than in the conventional and oil groups. Degree of procedural difficulty was lower in the warm water group, and patient pain score was higher in the oil lubrication group, compared with the other groups. However, there was no significant difference in success rate of intubation within time limit among the three groups. CONCLUSIONS: The warm water method is a simple, safe, and feasible method for beginners. Oil lubrication may not be a useful method compared with conventional and warm water method.

Tectorigenin inhibits IFN-gamma/LPS-induced inflammatory responses in murine macrophage RAW 264.7 cells.

Tectorigenin (Tg) and tectoridin (Td) are the major compounds isolated from the rhizomes of iridaceous plant Belamcanda chinensis which is well known as a chinese traditional medicine for the treatment of inflammatory diseases. In this study we investigated whether tectorigenin and tectoridin can be applied to the suppression of interferon-gamma and lipopolysaccharide (IFN-gamma/LPS)-induced inflammatory responses in macrophages. Anti-inflammatory activities of tectorigenin and tectoridin were compared with genistein (Ge), well known isoflavonoid as a phytoestrogen and regarded as an emerging anti-inflammatory agent. Both compounds showed low cytotoxic effect. In Raw 264.7 cells activated with IFN-gamma/LPS, pre-treated tectorigenin was found to inhibit the expression of inducible nitric oxide synthase (iNOS), the production of nitric oxide (NO) and the secretion of interleukin (IL)-1beta dose-dependently. Tectorigenin also decreased the expression of cyclooxigenase (COX)-2 and the production of prostaglandin E(2) (PGE(2)) in dose-dependent manner. These inhibitory effects of tectorigenin were found to be caused by the blocking of nuclear factor kappa-B (NF-kappaB) activation. Compared with genistein and tectoridin, tectorigenin showed significant inhibitory effect for almost anti-inflammatory tests in this study. All these results clearly demonstrated that tectorigenin appears to have the potential to prevent inflammation.