Clinical features of community-acquired <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> urinary tract infections in children

This retrospective chart review sought to determine clinical, radiological, and gender-associated characteristics of community-acquired Pseudomonas aeruginosa (PA) urinary tract infections (UTIs) among children admitted to two medical centers. The records of 73 children with community-acquired PA UTIs were compared with records of 109 children with community-acquired UTIs caused by other pathogens. The mean age of both groups was similar. The PA UTI group included more boys. Features significantly more common in the PA UTI group were the number of patients who had undergone urinary tract surgery, patients with skeletal and/or neurological malformation, patients with >1 previous episode of UTI, patients on prophylactic antibiotic treatment on admission, and patients with pathological renal ultrasound and voiding cystourethrography (VCUG) findings. Multivariate logistic regression analysis revealed the following to be associated with PA UTI: >1 episode of UTI in the past [odds ratio (OR) = 35.5; 95% confidence interval (CI) 11.6–108.7], previous urinary tract surgery (OR = 34.1; 95% CI 7.00–166.2), and pathological VCUG results (OR = 2.62; 95% CI 0.96–7.15). In conclusion, PA UTI is associated with >1 previous UTI, urinary tract abnormalities, and past urinary tract surgery. We recommend that when UTI is suspected in children with these risk factors, a thorough radiologic investigation, including a VCUG, should be considered. Drs. Goldman and Rosenfeld-Yehoshua contributed equally to this work.     

Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation

BACKGROUND Arachidyl amido cholanoic acid(Aramchol) is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1) protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis. In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH), 52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c, an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model [induced with a 0.1% methionine and choline deficient diet(0.1 MCD)] after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20 μmol/L Aramchol or vehicle for 48 h. Subsequently, analyses were performed including Western blot, proteomics by mass spectrometry, and fluxomic analysis with ~(13)C-uniformly labeled glucose. For the in vivo part of the study, male C57 BL/6 J mice were randomly fed a control or 0.1 MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk. Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes. This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA) synthesis and oxidation [PACCα/β(S79), SCD1, CPT1A/B, HADHA, and HADHB], oxidative phosphorylation(NDUFA9, NDUFB11, NDUFS1, NDUFV1, ETFDH, and UQCRC2), tricarboxylic acid(TCA) cycle(MDH2, SUCLA2, and SUCLG2), and ribosome(P-p70S6K[T389] and P-S6[S235/S236]). Flux experiments with ~(13)C uniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes, as indicated by the increase in the number of rounds that malate remained in the TCA cycle. Finally, liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1 MCD fed mice in a dose-dependent manner, showing normalization of glucose, G6P, F6P, UDP-glucose, and Rbl5 P/Xyl5 P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1, which in turn activate FA β-oxidation and oxidative phosphorylation.     

Salivary bacteria and oral health status in medicated and non-medicated children and adolescents with attention deficit hyperactivity disorder (ADHD)

Objectives

Attention deficit hyperactivity disorder (ADHD) is a childhood neurological disorder. Studies have shown that children with ADHD are more prone to caries than those without. The study investigated children diagnosed with ADHD, both with and without pharmacological intervention, and the following: DMFT\dmft, plaque index (PI), mutans streptococci (MS) levels, lactobacilli (LB) levels, salivary flow, salivary buffer capacity, oral hygiene, and diet.

Study design

DMFT/dmft index, PI, MS and LB levels, salivary flow, and salivary buffer capacity were examined in three groups of children: ADHD1—diagnosed with ADHD with no pharmacological intervention (N?=?31), ADHD2—treated with medications for ADHD (N?=?30), and a healthy control group (N?=?30). Diet and oral health habits were assessed through questionnaires completed by parents.

Results

There were no differences in the DMFT/dmft index, MS and LB counts, salivary buffer capacity, and parent reported diet and oral health behavior between the three groups. Children with ADHD demonstrated a higher plaque index.

Conclusions

Although children with ADHD did not report different diet and oral health behavior from children without ADHD, this group had significantly higher levels of plaque than the control group, which combined with hyposalivation may be a risk factor for caries at an older age.

Clinical relevance

Medicated and non-medicated ADHD children were similar to control children in their caries rate, MS and LB counts, salivary buffer capacity, and diet and oral health behavior. They differed in the amount of plaque found on their teeth. As a group, ADHD children demonstrated hyposalivation compared with the control.     

Pituitary-directed medical therapy with pasireotide for a corticotroph macroadenoma: pituitary volume reduction and literature review

Hypercortisolism due to an ACTH-secreting pituitary adenoma (Cushing’s disease) is a chronic condition associated with high morbidity and mortality if inadequately managed. Pasireotide is a multireceptor-targeted somatostatin analogue and is the only approved medical therapy for Cushing’s disease that treats the underlying cause of the disorder. This paper reviews the available literature for medical-therapy-induced adenoma volume reduction in patients with Cushing’s disease and reports the experience of a 53-year-old surgically, radiologically and medically naïve (de novo) female with a pituitary macroadenoma who declined surgery. This patient was treated with pasireotide as first-line therapy as part of the largest randomized Phase III study evaluating a medical therapy in patients with Cushing’s disease (SOM230B2305 trial). Subcutaneous pasireotide significantly decreased tumor volume, suppressed cortisol secretion, and improved clinical signs and symptoms of Cushing’s disease in this patient. Based on this experience, first-line pasireotide has the potential to achieve substantial tumor volume reduction in addition to significant improvements in cortisol levels and signs and symptoms in patients with Cushing’s disease for whom surgery is not an option.