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Hepatocellular adenomas (HCA) are benign tumours with potential for malignant transformation with no recommendations regarding management in the paediatric population. We report a case of an inflammatory adenoma with β-catenin activated pathway in an obese, paediatric patient with nonalcoholic steatohepatitis (NASH).Case Report: An 11-year-old female presented with a microlobulated liver lesion measuring >5 cm in magnetic resonance imaging (MRI) with inflammatory adenoma with β-catenin activated pathology arising in a background of NASH, nonalcoholic fatty liver disease (NAFLD) activity score 5/8. Imaging follow-up demonstrated stable disease without progression for 3 years.Discussion: Malignant transformation of Hepatocellular adenomas in a child is approximately 4.2%. It is unknown if hepatic steatosis increases this risk. Obese patients mainly develop inflammatory and β-catenin activated (highest risk for malignant transformation) adenomas. Our patient had inflammatory and β-catenin activation, which led to monitoring for malignant transformation.Conclusion: We report a β-catenin activated inflammatory adenoma in a child with obesity and NASH with ongoing expectant management. [ABSTRACT FROM AUTHOR]

Background Non-alcoholic steatohepatitis ( NASH) and resultant liver fibrosis is a major health problem without approved pharmacotherapy. Pre-clinical results of GR- MD-02, a galectin-3 inhibitor, suggested potential efficacy in NASH with advanced fibrosis/cirrhosis and prompted initiation of a clinical development programme in NASH with advanced fibrosis. Aim To evaluate the safety, pharmacokinetics and exploratory pharmacodynamic markers of GR- MD-02 in subjects having NASH with bridging fibrosis. Methods The GT-020 study was a first-in-human, sequential dose-ranging, placebo controlled, double-blinded study with the primary objective to assess the safety, tolerability and dose limiting toxicity of GR- MD-02, in subjects with biopsy-proven NASH with advanced fibrosis (Brunt stage 3). The secondary objectives were to characterise first-dose and multiple-dose pharmacokinetic profiles and to evaluate changes in potential serum biomarkers and liver stiffness as assessed by FibroScan. Results GR- MD-02 single and three weekly repeated of 2, 4 and 8 mg/kg revealed no meaningful clinical differences in treatment emergent adverse events, vital signs, electrocardiographic findings or laboratory tests. Pharmokinetic parameters showed a dose-dependent relationship with evidence of drug accumulation following 8 mg/kg (~twofold). Conclusions GR- MD-02 doses were in the upper range of the targeted therapeutic dose determined from pre-clinical data and were safe and well tolerated with evidence of a pharmacodynamic effect. These results provide support for a Phase 2 development programme in advanced fibrosis due to NASH. [ABSTRACT FROM AUTHOR]

Objective We conducted a randomized placebo-controlled trial to examine the effects of metformin on visceral adipose tissue (VAT), appendicular fat, lipid profile and insulin sensitivity in HIV-infected persons with central adiposity and mild insulin resistance. Methods Forty-eight HIV-infected men and women with a self-reported increase in abdominal girth and an abnormal waist-to-hip ratio were randomly assigned in double-blind fashion to receive metformin 1500 mg or placebo daily for 24 weeks. Persons with diabetes were excluded. The following measures were obtained at baseline and 24 weeks: single-slice computed tomography (CT) scan, dual-energy X-ray absorptiometry (DEXA), lipid profile and oral glucose tolerance test. Results The median fasting insulin concentration of all participants was 12.3 μU/mL. The percentage change in VAT was not significantly different between the metformin and placebo groups in univariate analysis and linear regression analysis adjusting for age, height, baseline VAT and insulin area under the curve (10.1% vs 3.2%; P=0.58). Metformin was associated with a significant decrease in appendicular fat mass compared with placebo (−686.0 vs 161.0 g; P=0.03). There was no significant change in lipid profile or insulin sensitivity between the two groups at 24 weeks. Conclusion Metformin should be used with caution in the treatment of HIV lipodystrophy, and, if used, should be reserved for persons with adequate peripheral fat and marked insulin resistance. [ABSTRACT FROM AUTHOR]

A study was conducted to determine the potential and nature of root-mediated allelopathic interference of Chenopodium murale on wheat. Early growth of wheat reduced significantly in agar medium where C. murale seedlings were previously growing as well as in rhizosphere soil of C. murale. The reduction in wheat growth was due to the presence of inhibitory metabolites released by roots of C. murale in the growth media. Even the soil incorporation of root residues also reduced the wheat growth in terms of seedling length and seedling dry weight. Only a partial amelioration in growth inhibition occurred upon charcoal supplementation or nitrogen fertilization in these amended soils. Root residues did not reduce the available nutrients in the soil, which was rather nutrient rich. These results indicated the definite role of allelopathy of C. murale roots in retarding wheat growth. Root amended soils contained significantly higher amount of phytotoxic phenolics as the putative allelochemicals, which were ferulic acid, vanillic acid, p-coumaric acid and benzoic acid. The study concluded that C. murale roots and their exudates exerted allelopathic effects on wheat by releasing water-soluble phenolic acids as putative allelochemicals in soil. [ABSTRACT FROM AUTHOR]

2-Benzoxazolinone (BOA), a type of hydroxamic acid present in cereals and implicated in allelopathy, is now being viewed as a potential candidate for the development of natural herbicides. A study was conducted to determine the effect of BOA on mung bean ( Phaseolus aureus) through a multitude of bioassays to understand its physiological and biochemical action. It was observed that BOA significantly decreased the germination of mung bean and its early growth (measured in terms of seedling length and dry weight). A typical dose–response relationship was observed with BOA treatment, and I50 values (concentrations at which 50% inhibition occurs) for germination, seedling length and seedling dry weight were calculated to be 4.3, 0.71 and 0.77 mM, respectively. There was therefore a greater inhibitory effect on seedling growth than on germination. Treated seedlings were characterised by a loss of chlorophyll and decreased respiratory activity, indicating a possible adverse effect of BOA on photosynthetic and respiratory metabolism. Mitotic activity in root-tip cells of onion ( Allium cepa) was completely arrested in response to BOA treatment, and the cells exhibited abnormality in shape and size. BOA also adversely affected rhizogenesis in hypocotyl cuttings of mung bean, indicating an impact on morphogenetic potential. It was associated with significant changes in the protein content and activities of proteases and polyphenol oxidases during the root development phase. This study concludes that BOA interfered with essential biochemical processes in mung bean. Such studies provide useful information on the biochemical and physiological modes of actions of BOA, with a view to its use as a herbicidal compound. [ABSTRACT FROM AUTHOR]

The herbicidal effect of volatile oils from leaves of Eucalyptus citriodora against the noxious weed Parthenium hysterophorus was tested. In a laboratory bioassay, seed germination and seedling length, chlorophyll content and respiratory activity of Parthenium decreased with increased concentration of eucalypt oils from 0.2 to 5.0 nL mL-1. Germination was completely inhibited at 5.0 nL mL-1 eucalyptus oils. Further, for 4-week-old plants of Parthenium sprayed with different concentrations of volatile oils, visible damage increased and chlorophyll content and respiratory activity decreased with increased concentration from 0 to 100 µL mL-1, the week after spraying. At concentrations up to 50 µL mL-1, plants showed some recovery over time but plants sprayed with 75 and 100 µL mL-1 died 2 weeks after treatment. Plants sprayed with 50 µL mL-1 and higher concentrations of eucalypt oils were desiccated and wilted in appearance. At concentrations of 5-75 µL mL-1, eucalypt oils caused a rapid electrolyte leakage from the Parthenium plants thereby indicating an effect on membrane integrity. It is concluded that volatile oils from E. citriodora possess weed-suppressing ability and could be used as a potential bioherbicide for future weed management programmes. [ABSTRACT FROM AUTHOR]

Aim: To determine the influence of gestation and weight on the development of protective anti-HB levels and geometric mean titres after three doses of HBV vaccine and to ascertain the need for a fourth dose in low birthweight infants.Methods: Hepatitis B vaccine (Enivac HB, Panacea Biotec Ltd., India) was given to 82 preterm (PT) and 60 term intrauterine growth-retarded (T-IUGR) infants at birth and at 6, 10 and 14wk of life.Results: Protective anti-HB levels (>10 mIU/ml) were reached in 86.6% (71/82) of PT infants and 96.7% (58/60) of T-IUGR infants after three doses of HBV vaccine (p = 0.044). The odds of having a protective response after the third dose of HBV vaccine was 1.25 (95% CI 1.02-1.53) with every one-week increase in gestation (p = 0.032). Birthweight was not associated with the development of a protective immune response. After the third dose, only 66.7% (8/12) of the PT infants whose mothers had anti-HB antibodies, developed protective anti-HB levels compared with 90% (63/70) of those with no maternal antibodies (p = 0.028). In PT infants after the fourth dose, there was a significant increase in the proportion of infants with protective antibody levels (8.6%, 95% CI 0.6-16.6%) among those with no maternal antibodies and 12.2% overall (95% CI 6.0-21.3) (p = 0.031 to 0.002) over that reached with the third dose. Administration of the fourth dose to T-IUGR infants did not confer such a benefit.Conclusion: In HBV-endemic areas, PT infants, irrespective of their birthweights, may benefit from an additional dose of hepatitis B vaccine in a schedule starting at birth. This approach will prevent vertical transmission and bring their immune response up to par with term infants. Term intrauterine growth-retarded infants should be vaccinated as per the schedule recommended for normal term infants. However, studies in other settings with different vaccine formulations and a longer follow-up period will be required before this strategy can be practised more widely. [ABSTRACT FROM AUTHOR]

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Unlabelled: Hepatic technetium-99m-mebrofenin iminodiacetate (99mTc-mebrofenin IDA) scans and serum gamma-glutamyl transpeptidase (GGTP) have high sensitivity for extrahepatic biliary atresia (EHBA). This study was based on the hypothesis that the interpretation of results of 99mTc-mebrofenin IDA scans and serum GGTP levels in series would result in a reduction of the false positivity observed with these tests individually. The aetiology of neonatal cholestasis in 132 study patients was: 25% (33/132) EHBA, 45.5% (60/132) neonatal hepatitis (NH) with an identifiable cause and 19.7% (26/132) idiopathic NH. Of the various clinical, biochemical and imaging parameters that were significantly different between patient groups, sensitivity for EHBA was: serum GGTP > or = 150 IU l(-1) (100%), 99mTc-mebrofenin IDA scans (100%), pale stools (82.8%) and total serum bilirubin > or = 12 mg dl(-1) (66%). However, specificity ranged from 48.5 to 79%. Of the 63 patients who had non-excreting IDA scans, operative cholangiograms could be avoided on the basis of a specific aetiological diagnosis of NH, made concurrently, in only 9 infants. The rest (54) underwent operative cholangiograms; 21 (39%) of these had patent biliary trees and therefore underwent the procedure unnecessarily. If serum GGTP (< 150 IU l(-1)) had been used as a screen after IDA scanning in these 54 patients, operative cholangiograms could have been avoided in another 12 patients and thereafter only 9/42 (21%) of the operative cholangiograms would have been considered unnecessary.Conclusion: A diagnostic algorithm is proposed wherein serum GGTP level (at a cut-off level that maintains 100% sensitivity for EHBA) is used in series with non-excreting 99mTc-mebrofenin IDA scans (for patients with no specific aetiological label). This strategy reduces the false positivity of individual tests. [ABSTRACT FROM AUTHOR]

Spray applications of 1000 mg/l (2‐chloroethyl)phosphonic acid (CEPA) five times, at weekly intervals, during November and early December induced heavy flowering in ringed and nonringed juvenile mango seedlings. The treated plants produced flower buds which opened by the end of December, while the control and ringed seedlings produced only a new flush of vegetative growth. The results show that CEPA could be profitably used for early evaluation of hybrid seedlings in mango breeding programme. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common paediatric liver disease. Latinos have high MASLD risk due to 50% prevalence of GG genotype of PNPLA3. Our primary aim was to evaluate associations between dietary carbohydrates/sugars and liver stiffness in Latino adolescents with obesity. Our secondary aim was to examine effect modification by (a) PNPLA3 genotype or (b) liver disease severity. Data were obtained from 114 Latino adolescents with obesity involved in two prior studies. No associations were seen between dietary carbohydrates/sugars and liver stiffness in the group as a whole. In subjects with GG genotype of PNPLA3, total sugar, fructose, sucrose, and glucose were associated with liver stiffness. Positive relationships between carbohydrate, total sugar, and sucrose and liver stiffness were stronger in those with MASLD and fibrosis compared to those with healthy livers and MASLD without fibrosis., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: This study aimed to assess the knowledge, attitudes, and practices surrounding the prescribing of opioids and addiction in a dental school population., Methods: Predoctoral dental students, residents, and dental faculty were surveyed about their beliefs, awareness, opinions about, and prior training in the prescribing of opioids, current prescribing practices, and confidence with risk mitigation strategies. Demographic information collected included gender, race/ethnicity, faculty/student role, year of birth, and year of graduation., Results: Responses were received from 220 faculty and students (n = 47 and n = 173, respectively). Both faculty and students agreed that opioids were overprescribed for the treatment of dental pain. A majority of faculty and dental students (DS)3 + DS4 and DS1 + DS2 students expressed no or limited prior training in (1) the approved state opioid guidelines (75%, 79%, and 95%, respectively), (2) the identification/assessment of substance use disorders (68%, 81%, and 92%, respectively), and (3) patient education to accompany the prescribing of opioids (71%, 80%, and 92%, respectively). A majority of faculty reported moderate or extreme confidence in their clinical skills related to the prescribing of opioids (75%), their ability to identify patients with substance use disorders (55%), and their ability to discuss addiction risk and secure storage of opioids (65%). In contrast, DS3 + DS4 and DS1 + DS2 students expressed significantly less confidence and training. Faculty and students agreed that the role of a dentist included risk mitigation, but reported actions did not match their beliefs, reportedly due to lack of time, less confidence, and the assumption that a pharmacist would assume risk mitigation conversations., Conclusions: A cohesive curriculum across the four predoctoral years is needed focusing on factual knowledge about the prescribing of opioids, safe prescribing, and confidence with patient communication and risk mitigation strategies. In addition, a need for parallel faculty development synchronized with and reinforced by curricular content was identified., (© 2021 American Dental Education Association.)

Background & Aims: C-Jun N-terminal kinase (JNK) activation is pivotal in the development of nonalcoholic steatohepatitis (NASH). Mixed lineage kinase 3 (MLK) 3 is one of the mitogen activated protein kinase kinase kinase (MAP3K) that mediates JNK activation in the liver. Despite this concept, the role of MLK3 in modulating liver injury during nutrient excess has not been explored. Our aim was to determine if MLK3 deficient mice were protected against high fat high carbohydrate (HFHC) diet-induced NASH., Methods: We employed eight-week-old Mlk3(-/-) male C57BL/6J mice, and wild type (WT) mice C57BL/6J as controls. Mice were fed a HFHC or a chow diet adlib for 16 weeks., Results: Hepatic JNK activating phosphorylation was readily absent in the Mlk3(-/-) mice fed the HFHC diet, but not in WT mice. This inhibition of JNK activation was hepatoprotective. Despite a comparable increase in weight gain, hepatic steatosis by histological examination and hepatic triglyceride quantification was reduced in HFHC diet-fed Mlk3(-/-) mice compared with WT mice. In addition, compared with the WT mice, HFHC diet-fed Mlk3(-/-) mice had significantly attenuated liver injury as manifested by reduced ALT levels, hepatocyte apoptosis, markers of hepatic inflammation and indices of hepatic fibrogenesis., Conclusion: Our results suggest that loss of MLK3 in mice is protective against HFHC diet-induced NASH, in a weight-independent fashion, through attenuation of JNK activation. MLK3 is a potential therapeutic target for the treatment of human NASH., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)