Developmental regulation of cellular metabolism is required for intestinal elongation and rotation.

Malrotation of the intestine is a prevalent birth anomaly, the etiology of which remains poorly understood. Here, we show that late-stage exposure of Xenopus embryos to atrazine, a widely used herbicide that targets electron transport chain (ETC) reactions, elicits intestinal malrotation at high frequency. Interestingly, atrazine specifically inhibits the cellular morphogenetic events required for gut tube elongation, including cell rearrangement, differentiation and proliferation; insufficient gut lengthening consequently reorients the direction of intestine rotation. Transcriptome analyses of atrazine-exposed intestines reveal misexpression of genes associated with glycolysis and oxidative stress, and metabolomics shows that atrazine depletes key glycolytic and tricarboxylic acid cycle metabolites. Moreover, cellular bioenergetics assays indicate that atrazine blocks a crucial developmental transition from glycolytic ATP production toward oxidative phosphorylation. Atrazine-induced defects are phenocopied by rotenone, a known ETC Complex I inhibitor, accompanied by elevated reactive oxygen species, and rescued by antioxidant supplementation, suggesting that malrotation may be at least partly attributable to redox imbalance. These studies reveal roles for metabolism in gut morphogenesis and implicate defective gut tube elongation and/or metabolic perturbations in the etiology of intestinal malrotation.

An adaptive teosinte mexicana introgression modulates phosphatidylcholine levels and is associated with maize flowering time.

Native Americans domesticated maize (Zea mays ssp. mays) from lowland teosinte parviglumis (Zea mays ssp. parviglumis) in the warm Mexican southwest and brought it to the highlands of Mexico and South America where it was exposed to lower temperatures that imposed strong selection on flowering time. Phospholipids are important metabolites in plant responses to low-temperature and phosphorus availability and have been suggested to influence flowering time. Here, we combined linkage mapping with genome scans to identify High PhosphatidylCholine 1 (HPC1), a gene that encodes a phospholipase A1 enzyme, as a major driver of phospholipid variation in highland maize. Common garden experiments demonstrated strong genotype-by-environment interactions associated with variation at HPC1, with the highland HPC1 allele leading to higher fitness in highlands, possibly by hastening flowering. The highland maize HPC1 variant resulted in impaired function of the encoded protein due to a polymorphism in a highly conserved sequence. A meta-analysis across HPC1 orthologs indicated a strong association between the identity of the amino acid at this position and optimal growth in prokaryotes. Mutagenesis of HPC1 via genome editing validated its role in regulating phospholipid metabolism. Finally, we showed that the highland HPC1 allele entered cultivated maize by introgression from the wild highland teosinte Zea mays ssp. mexicana and has been maintained in maize breeding lines from the Northern United States, Canada, and Europe. Thus, HPC1 introgressed from teosinte mexicana underlies a large metabolic QTL that modulates phosphatidylcholine levels and has an adaptive effect at least in part via induction of early flowering time.

Clinical experience of infantile hepatic hemangioma.

PURPOSE: To describe the clinical presentation, treatment preference, and relevant complications of infantile hepatic hemangioma (IHH) in propranolol era. METHODS: The National Taiwan University Hospital integrated Medical Database (NTUH-iMD) was used to enroll twenty-one cases of IHH diagnosed from 2006 to 2020. Medical charts were retrospectively reviewed. RESULTS: In nine patients (42.9%), IHH was found incidentally, and in seven patients (33%), it was detected during postnatal self-paid ultrasonography. Focal disease was determined in 17 patients, multifocal disease in 1 patient, and diffuse disease in 3 patients. Patients with diffuse disease had a lower hemoglobulin level than patients with focal IHH (9.38 vs. 12.6 mg/dL, p = 0.045). Two patients had Kasabach-Merritt phenomenon (KMP), one had hypothyroidism, and one had both. All patients with KMP had focal hepatic hemangiomas. Among the 17 patients with focal IHH, nine were prescribed propranolol, one was treated by surgical resection of the tumor, and the others had expectant management. All patients with multifocal and diffuse IHH were administered propranolol. One infant (7.7%) treated with propranolol had bradycardia initially but it subsided after dose adjustment. CONCLUSIONS: Most IHH is found incidentally or detected during postnatal ultrasonography screening. Patients with large focal lesions should also be screened for associated complications. Propranolol is the drug of choice and a safe therapeutic option for IHH, especially for focal tumors >5 cm as well as multifocal and diffuse lesions.

The effects of job characteristics on physicians' orientation toward lifelong learning.

With the rapidly growing body of medical knowledge, physicians must engage in lifelong learning. Physicians' orientation toward lifelong learning is of crucial importance. This study aimed to explore the effects of job characteristics on physicians' lifelong learning. A multicenter study collecting data from physicians from three medical centers in Taiwan was performed. A total of 321 physicians were surveyed with the Chinese version of the Job Content Questionnaire (C-JCQ) and the revised Jefferson Scale of Physician Lifelong Learning (JeffSPLL) to assess their job characteristics (i.e., job demands, job control, social support) and orientation toward lifelong learning. Exploratory factor analysis was employed to validate both questionnaires. Hierarchical regression was utilized to explore the relationship of job characteristics and predictors with physicians' lifelong learning. The results revealed that job demands (ß = 0.10), job control (ß = 0.19), social support from supervisors (ß = 0.16), the interaction of job demands × job control (ß = - 0.11) and the interaction of job demands × social support from colleagues (ß = 0.13) were significantly (p < .05, p < .001) related to lifelong learning. Moreover, physicians in the active group (high demand, high control) possessed a stronger orientation toward lifelong learning (mean = 3.57) than those in the low-strain group (mean = 3.42), high-strain group (mean = 3.39) and passive group (mean = 3.20). In conclusion, examining physicians' job demands, job control and social support helps us to understand their orientation toward lifelong learning and may provide insight to improve educational strategies.

Is the rating result reliable? A new approach to respond to a medical trainee's concerns about the reliability of Mini-CEX assessment.

PURPOSE: Whether the rating result of mini-clinical evaluation exercise (Mini-CEX) for rating clinical skills is reliable is of a medical trainee's great concerns. The objectives of this study were to analyze the test-retest reliability, interrater reliability and internal consistency reliability of Mini-CEX. METHODS: Three clinical scenarios, each played by a standardized patient and resident, were developed and videotaped. A group of assessors were recruited to rate the resident's clinical skills using Mini-CEX with a nine-point grading scale in each videotaped clinical scenario. Each assessor was required: (1) to watch the videotaped clinical scenarios a sequential order; (2) to rate each medical trainee's clinical skills in each clinical scenario for two rating sessions, and there must be a minimum three-week interval between the first and the second Mini-CEX rating session. RESULTS: A total of 38 assessors participated in this study. This study showed that: (1) an assessor carried out similar rating reuslts under the same clinical performance based on an acceptable test-retest reliability (Pearson's correlation coefficients = 0.24-0.76, P value=<0.01-0.14); (2) assessors gave similar rating results to a medical trainee's clinical performance based on a good interrater reliability (intra-class correlation coefficient = 0.57-0.83, P value=<0.01-0.03); and (3) the items reflected unidimensionally a construct-a medical trainee's clinical skills based on an excellent internal consistency reliability (Cronbach's alpha = 0.92-0.97). CONCLUSION: This study convincingly showed that Mini-CEX is a reliable assessment tool for rating clinical skills, and can be widely used to assess medical trainees' clinical skills.

Neuropeptide S-initiated sequential cascade mediated by OX1, NK1, mGlu5 and CB1 receptors: a pivotal role in stress-induced analgesia.

BACKGROUND: Stress-induced analgesia (SIA) is an evolutionarily conserved phenomenon during stress. Neuropeptide S (NPS), orexins, substance P, glutamate and endocannabinoids are known to be involved in stress and/or SIA, however their causal links remain unclear. Here, we reveal an unprecedented sequential cascade involving these mediators in the lateral hypothalamus (LH) and ventrolateral periaqueductal gray (vlPAG) using a restraint stress-induced SIA model. METHODS: Male C57BL/6 mice of 8-12 week-old were subjected to intra-cerebroventricular (i.c.v.) and/or intra-vlPAG (i.pag.) microinjection of NPS, orexin-A or substance P alone or in combination with selective antagonists of NPS receptors (NPSRs), OX1 receptors (OX1Rs), NK1 receptors (NK1Rs), mGlu5 receptors (mGlu5Rs) and CB1 receptors (CB1Rs), respectively. Antinociceptive effects of these mediators were evaluated via the hot-plate test. SIA in mice was induced by a 30-min restraint stress. NPS levels in the LH and substance P levels in vlPAG homogenates were compared in restrained and unrestrained mice. RESULTS: NPS (i.c.v., but not i.pag.) induced antinociception. This effect was prevented by i.c.v. blockade of NPSRs. Substance P (i.pag.) and orexin-A (i.pag.) also induced antinociception. Substance P (i.pag.)-induced antinociception was prevented by i.pag. Blockade of NK1Rs, mGlu5Rs or CB1Rs. Orexin-A (i.pag.)-induced antinociception has been shown previously to be prevented by i.pag. blockade of OX1Rs or CB1Rs, and here was prevented by NK1R or mGlu5R antagonist (i.pag.). NPS (i.c.v.)-induced antinociception was prevented by i.pag. blockade of OX1Rs, NK1Rs, mGlu5Rs or CB1Rs. SIA has been previously shown to be prevented by i.pag. blockade of OX1Rs or CB1Rs. Here, we found that SIA was also prevented by i.c.v. blockade of NPSRs or i.pag. blockade of NK1Rs or mGlu5Rs. Restrained mice had higher levels of NPS in the LH and substance P in the vlPAG than unrestrained mice. CONCLUSIONS: These results suggest that, during stress, NPS is released and activates LH orexin neurons via NPSRs, releasing orexins in the vlPAG. Orexins then activate OX1Rs on substance P-containing neurons in the vlPAG to release substance P that subsequently. Activates NK1Rs on glutamatergic neurons to release glutamate. Glutamate then activates perisynaptic mGlu5Rs to initiate the endocannabinoid retrograde inhibition of GABAergic transmission in the vlPAG, leading to analgesia.

Are physicians on the same page about do-not-resuscitate? To examine individual physicians' influence on do-not-resuscitate decision-making: a retrospective and observational study.

BACKGROUND: Individual physicians and physician-associated factors may influence patients'/surrogates' autonomous decision-making, thus influencing the practice of do-not-resuscitate (DNR) orders. The objective of this study was to examine the influence of individual attending physicians on signing a DNR order. METHODS: This study was conducted in closed model, surgical intensive care units in a university-affiliated teaching hospital located in Northern Taiwan. The medical records of patients, admitted to the surgical intensive care units for the first time between June 1, 2011 and December 31, 2013 were reviewed and data collected. We used Kaplan-Meier survival curves with log-rank test and multivariate Cox proportional hazards models to compare the time from surgical intensive care unit admission to do-not-resuscitate orders written for patients for each individual physician. The outcome variable was the time from surgical ICU admission to signing a DNR order. RESULTS: We found that each individual attending physician's likelihood of signing do-not-resuscitate orders for their patients was significantly different from each other. Some attending physicians were more likely to write do-not-resuscitate orders for their patients, and other attending physicians were less likely to do so. CONCLUSION: Our study reported that individual attending physicians had influence on patients'/surrogates' do-not-resuscitate decision-making. Future studies may be focused on examining the reasons associated with the difference of each individual physician in the likelihood of signing a do-not-resuscitate order.

To examine the associations between medical students' conceptions of learning, strategies to learning, and learning outcome in a medical humanities course.

BACKGROUND: By learning medical humanities, medical students are expected to shift from handling the diseases only to seeing a whole sick person. Therefore, understanding medical students' learning process and outcomes of medical humanities becomes an essential issue of medical education. Few studies have been conducted to explore factors surrounding medical students' learning process and outcomes of medical humanities. The objectives were: (1) to investigate the relationships between medical students' conceptions of learning and strategies to learning; and (2) to examine the relationships between students' strategies to learning and learning outcomes for medical humanities. METHODS: We used the modified Approaches to Learning Medicine (mALM) questionnaire and Conceptions of Learning Medicine (COLM) questionnaire to measure the medical students' strategies to learning and conceptions of learning respectively. The learning outcome of medical humanities was measured using students' weighted grade in a medical humanities course. The confirmatory factor analysis (CFA) was used to validate the COLM and mALM questionnaires, in which construct validity and reliability were assessed. Pearson's correlation was used to examine the relationships among the factors of COLM, mALM, and the weighted grade. Path analysis using structural equation modeling technique (SEM) was employed to estimate the structural relationships among the COLM, mALM, and the weighted grade. RESULTS: Two hundred and seventy-five first-year medical students consented to participate in this study. The participants adopting surface strategies to learning were more likely to have unsatisfactory learning outcome (ß = - 0.14, p = .04). The basic-level conception of "Preparing for Testing" was negatively (ß = - 0.19, p < .01) associated with deep strategies of learning, and positively (ß = 0.48, p < .01) associated with surface strategies of learning (ß = 0.50, p < .01). The basic-level conception of "Skills Acquisition" was positively associated with deep strategies of learning (ß = 0.23, p < .01). CONCLUSION: Medical educators should wisely employ teaching strategies to increase students' engagement with deep and self-directed learning strategies, and to avoid using surface learning strategies in the medical humanities course in order to achieve better learning outcomes.

Targeted Metabolomic and Transcriptomic Analyses of "Red Russian" Kale (Brassicae napus var. pabularia) Following Methyl Jasmonate Treatment and Larval Infestation by the Cabbage Looper (Trichoplusia ni Hübner).

Methyl jasmonate (MeJA), synthesized in the jasmonic acid (JA) pathway, has been found to upregulate glucosinolate (GS) biosynthesis in plant species of the Brassicaceae family. Exogenous application of MeJA has shown to increase tissue GS concentrations and the formation of myrosinase-mediated GS hydrolysis products (GSHPs). In vitro and in vivo assays have demonstrated the potential health-promoting effects of certain GSHPs. MeJA is also known to elicit and induce genes associated with defense mechanisms to insect herbivory in Brassica species. To investigate the relationship between MeJA-induced GS biosynthesis and insect defense, three treatments were applied to "Red Russian" kale (Brassicae napus var. pabularia) seedlings: (1) a 250 µM MeJA leaf spray treatment; (2) leaf infestation with larvae of the cabbage looper (Trichoplusia ni (Hübner)); (3) control treatment (neither larval infestation nor MeJA application). Samples of leaf tissue from the three treatments were then assayed for changes in GS and GSHP concentrations, GS gene biosynthesis expression, and myrosinase activity. Major differences were observed between the three treatments in the levels of GS accumulation and GS gene expression. The insect-damaged samples showed significantly lower aliphatic GS accumulation, while both MeJA and T. ni infestation treatments induced greater accumulation of indolyl GS. The gene expression levels of CYP81F4, MYB34, and MYB122 were significantly upregulated in samples treated with MeJA and insects compared to the control group, which explained the increased indolyl GS concentration. The results suggest that the metabolic changes promoted by MeJA application and the insect herbivory response share common mechanisms of induction. This work provides potentially useful information for kale pest control and nutritional quality.

Predictors of hepatitis B e antigen-negative hepatitis in chronic hepatitis B virus-infected patients from childhood to adulthood.

UNLABELLED: Hepatitis B e antigen (HBeAg)-negative hepatitis is a clinical indicator of poor outcome for chronic hepatitis B viral (HBV) infection. This long-term prospective cohort study aimed to elucidate the predictors of developing HBeAg-negative hepatitis in chronic HBV-infected subjects followed from childhood to adulthood. We followed 434 HBeAg-positive chronic HBV-infected patients from a median age of 7.22 years (interquartile range 4.31-10.21 years). Spontaneous HBeAg seroconversion occurred in 359 subjects at a median age of 13.93 years (interquartile range 8.76-20.59 years), and 75 subjects developed HBeAg seroconversion after antiviral therapy. These patients were followed for a median of 14.40 years (interquartile range 6.14-22.02 years) after HBeAg seroconversion. Clinical data were analyzed to delineate the predictors of developing HBeAg-negative hepatitis. The HBV basal core promoter and precore/core gene sequences were also evaluated in subjects with and without HBeAg-negative hepatitis. The overall annual incidence of HBeAg-negative hepatitis was 0.37% (95% confidence internal 0.35-0.39) in spontaneous HBeAg seroconverters. The overall annual incidence of HBeAg-negative hepatitis increased to 2.64% in lamivudine-treated subjects but did not increase in those treated with interferon-alpha (0.58%). Male gender (hazard ratio = 3.15), HBV genotype C (hazard ratio = 4.40), HBeAg seroconversion after 18 years of age (hazard ratio = 2.46), and lamivudine therapy prior to HBeAg seroconversion (hazard ratio = 1.42) were predictors of HBeAg-negative hepatitis in HBeAg seroconverters (P < 0.05). HBeAg-negative hepatitis subjects carried more A1762T/G1764A, C2063A, and A2131C HBV gene mutations than those without HBeAg-negative hepatitis. CONCLUSIONS: HBeAg seroconversion during childhood predicts a lower risk of HBeAg-negative hepatitis in later life. Interferon-alpha therapy may be an effective antiviral therapy beneficial in chronic HBV-infected children with severe inflammation that facilitates HBeAg seroconversion in earlier life.

The effects of cytokines on spontaneous hepatitis B surface antigen seroconversion in chronic hepatitis B virus infection.

We examined the role of human cytokines in the natural course of hepatitis B surface Ag (HBsAg) seroconversion in chronic hepatitis B virus (HBV) infection. The clinical course of spontaneous HBsAg seroconversion was assessed in 296 chronically HBV-infected patients. Single nucleotide polymorphisms (SNPs) in IL-1ß, IL-2, IL-4, IL-10, IL-12ß, IL-13, IL-27, and IFN-γ genes were examined in 296 chronically HBV-infected patients and another 193 HBV recoverers. The HBsAg a determinant sequence of chronically HBV-infected subjects with and without HBsAg seroconversion was also analyzed. The start of the immune-clearance phase (serum alanine aminotransferase levels > 30 IU/l) before the age of 48 mo and hepatitis B e Ag (HBeAg) seroconversion before the age of 10 y predicted spontaneous HBsAg seroconversion in chronically HBV-infected patients (odds ratios 17.7 and 5.0; p < 0.001 and p < 0.002, respectively). The A-allele of IL-10 SNP rs1800872 was associated with higher IL-10 serum levels, and the G-allele of IL-12ß SNP rs3212217 was associated with sustained high serum IL-12p70 levels during the immune-clearance phase. Both were predictors of spontaneous HBsAg seroconversion and HBV recovery (odds ratios 4.0 and 26.3; p = 0.002 and p < 0.001, respectively). Spontaneous HBsAg seroconversion was not related to sex, HBV genotype, or HBsAg a determinant mutation. The start of immune-clearance phase, age at HBeAg seroconversion, and serum IL-10 and IL-12 levels are associated with the course of the immune-clearance phase in chronic HBV infection, and are predictive of spontaneous HBsAg seroconversion and HBV recovery.

Cultivar-Specific Changes in Primary and Secondary Metabolites in Pak Choi (Brassica Rapa, Chinensis Group) by Methyl Jasmonate.

Glucosinolates, their hydrolysis products and primary metabolites were analyzed in five pak choi cultivars to determine the effect of methyl jasmonate (MeJA) on metabolite flux from primary metabolites to glucosinolates and their hydrolysis products. Among detected glucosinolates (total 14 glucosinolates; 9 aliphatic, 4 indole and 1 aromatic glucosinolates), indole glucosinolate concentrations (153-229%) and their hydrolysis products increased with MeJA treatment. Changes in the total isothiocyanates by MeJA were associated with epithiospecifier protein activity estimated as nitrile formation. Goitrin, a goitrogenic compound, significantly decreased by MeJA treatment in all cultivars. Changes in glucosinolates, especially aliphatic, significantly differed among cultivars. Primary metabolites including amino acids, organic acids and sugars also changed with MeJA treatment in a cultivar-specific manner. A decreased sugar level suggests that they might be a carbon source for secondary metabolite biosynthesis in MeJA-treated pak choi. The result of the present study suggests that MeJA can be an effective agent to elevate indole glucosinolates and their hydrolysis products and to reduce a goitrogenic compound in pak choi. The total glucosinolate concentration was the highest in "Chinese cabbage" in the control group (32.5 µmol/g DW), but indole glucosinolates increased the greatest in "Asian" when treated with MeJA.

Factors affecting the natural decay of hepatitis B surface antigen in children with chronic hepatitis B virus infection during long-term follow-up.

OBJECTIVE: To investigate the factors predicting spontaneous clearance of hepatitis B surface antigen (HBsAg) in a long-term, prospectively followed cohort from childhood into adult life. STUDY DESIGN: Children with chronic hepatitis B virus (HBV) infection without treatment were followed longitudinally every 6 months. At each visit, liver profiles and HBV markers were assessed. Hepatitis B vaccination history and the maternal HBV markers also were studied. RESULTS: A total of 349 children (205 male) were followed for 20.6 ± 4.4 years with initial ages of 8.4 ± 3.9 years; 42 (12.0%) cleared HBsAg spontaneously. The HBsAg titers decayed with age, with an average annual clearance rate of 0.58%. Children had a lower annual HBsAg decay rate if their mothers are HBsAg carriers (P < .001). Hepatitis B e antigen-seroconversion is a favorable predictor for spontaneous HBsAg clearance (P = .04). Those with HBsAg titer ≤1000 IU/mL at enrollment during childhood have a higher rate of HBsAg clearance (hazard ratio = 5.23; P < .001). Using HBsAg titer ≤1000 IU/mL to predict HBsAg clearance, the sensitivity is 38.1%, specificity is 90.6%, positive predictive value is 35.6%, and negative predictive value is 91.4%. CONCLUSIONS: During long-term follow-up, spontaneous HBsAg clearance is most likely to occur in a patient born to a non-HBsAg-carrier mother, is a hepatitis B e antigen-seroconverter, and had an initial HBsAg level ≤1000 IU/mL.

Different clinical and genetic features of Alagille patients with progressive disease versus a jaundice-free course.

Background and Aim: Alagille syndrome (ALGS) is a multisystem disorder with variable clinical courses. This study investigated the clinical and genetic features of ALGS patients with different outcomes and analyzed the liver pathology at liver transplantation (LT) compared with that in biliary atresia (BA). Methods: We report the clinical characteristics, outcomes, and genetic mutations of 25 children with ALGS followed for a median of 7.3 years. Patients were classified into (i) jaundice-free (JF) group (resolving jaundice after 2 years of age); (ii) progressive disease (PD) group (persistent jaundice or progressive cholestasis). In addition, we analyzed the explant liver in 10 ALGS patients compared with 20 age-matched BA patients at the time of LT. Results: Nine patients (36%) in the JF group had a favorable outcome, with longer native liver survival than patients with PD (n = 16, P < 0.001). Fourteen of the PD group patients received LT or died. We identified 18 different JAG1 mutations in 22 patients. Three unrelated probands in the JF group had the same de novo mutation in JAG1, c.2122-2125delCAGT. Compared with BA children, ALGS patients had lower METAVIR scores in liver pathology, higher serum albumin levels, and lower weight-for-age z-scores when receiving LT. Conclusion: One-third of ALGS patients had JF and a favorable course. Children with ALGS presenting with persistent jaundice beyond 2 years of age should be cautioned for poor prognosis. ALGS patients tend to have a lesser extent of cirrhosis, and more growth problems than BA patients at the time of LT.

The characteristics of pediatric ulcerative colitis with primary sclerosing cholangitis: A single-center study in Taiwan.

BACKGROUND: Primary sclerosing cholangitis (PSC) is often associated with ulcerative colitis (UC). We investigated the clinical characteristics of pediatric UC patients with and without PSC. METHODS: We retrospectively recruited children with UC, with and without PSC, from 2006 to 2017 in a tertiary center in Taiwan. The clinical data of the patients, including clinical and endoscopic UC severity scores, medications, and laboratory parameters, were analyzed. RESULTS: We recruited five children with PSC-UC (PSC-UC group), and 26 with UC alone (non-PSC UC group) in this retrospective analysis. Among the patients with PSC-UC, four (80%) were compatible with definite or probable autoimmune sclerosing cholangitis (ASC). The UC Endoscopic Index of Severity (5.00 vs. 9.00, P = 0.003) and Mayo score (4.00 vs. 8.00, P = 0.014) were significantly lower in the PSC-UC group than the non-PSC UC group. The prevalence of immunomodulator use was significantly higher in the PSC-UC than the non-PSC UC group (100% vs. 42.3%, P = 0.043), but there was no difference regarding steroids, mesalamine, or biologics. At the end of the study, significantly fewer patients were steroid-free in the PSC-UC than the non-PSC UC group (20.0% vs. 84.6%, P = 0.010). CONCLUSIONS: Pediatric patients with PSC-UC had less severe colitis than those with UC alone in terms of the clinical activity index and endoscopic severity index, but they were more likely to need an immunomodulator and less likely to be steroid-free in the long term, for the control of liver disease.

Methyl Jasmonate Treatment of Broccoli Enhanced Glucosinolate Concentration, Which Was Retained after Boiling, Steaming, or Microwaving.

Exogenous methyl jasmonate (MeJA) treatment was known to increase the levels of neoglucobrassicin and their bioactive hydrolysis products in broccoli (Brassica oleracea var. italica), but the fate of MeJA-induced glucosinolates (GSLs) after various cooking methods was unknown. This study measured the changes in GSLs and their hydrolysis compounds in broccoli treated with MeJA and the interaction between MeJA and cooking treatments. All cooked MeJA-treated broccoli contained significantly more GSLs than untreated broccoli (p < 0.05). After 5 min of cooking (boil, steam, microwave), MeJA-treated broccoli still contained 1.6- to 2.3-fold higher GSL content than untreated broccoli. Neoglucobrassicin hydrolysis products were also significantly greater in steamed and microwaved MeJA-treated broccoli. The results show that exogenous MeJA treatment increases neoglucobrassicin and its hydrolysis compounds in broccoli even after cooking. Once the positive and negative effects of these compounds are better understood, the results of this experiment can be a valuable tool to help food scientists, nutrition scientists, and dieticians determine how to incorporate raw or cooked broccoli and Brassica vegetables in the diet.

AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases.

BACKGROUND: Inborn errors of bile acid metabolism (IEBAM) cause rare but treatable genetic disorders that can present as neonatal cholestasis or neurological diseases. Without timely primary bile acid treatment, patients may develop liver failure early in life. This study aimed to analyze the types and treatment outcomes of IEBAM in Taiwanese infants and document the allele frequency of CYP7B1 hot spot mutations in the population. METHODS: Urine samples from patients with infantile intrahepatic cholestasis and suspected IEBAM were subjected to urinary bile acid analysis by gas chromatography-mass spectrometry (GC/MS). Genetic diagnoses were made using direct sequencing or next-generation sequencing. We also tested healthy control subjects for a probable hot spot point mutation of CYP7B1. RESULTS: Among the 75 patients with infantile intrahepatic cholestasis tested during 2000 -2016, three had ∆4-3-oxosteroid 5ß-reductase deficiency with AKR1D1 mutations, and three had oxysterol-7α-hydroxylase deficiency with CYP7B1 mutation. Two patients with ∆4-3-oxosteroid 5ß-reductase deficiency were successfully treated with cholic acid. The three unrelated infants with oxysterol 7α-hydroxylase deficiencies had the same p.R112X homozygous CYP7B1 mutation. Two had mild renal or neurological involvement. Among 608 healthy control subjects, the allele frequency of the heterozygous mutation for p.R112X was 2/1216 (0.16%). The only surviving patient with oxysterol 7α-hydroxylase deficiency recovered from liver failure after chenodeoxycholic acid (CDCA) treatment beginning at 3 months of age. CONCLUSION: Distinct types of IEBAM disease were found in the Taiwanese population. Patients with early diagnosis and early treatment had a favorable outcome. IEBAM prevalence rates may be higher than expected due to the presence of heterozygous mutations in the general population.