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Growing clinical evidence represented that certain dietary components are involved in inflammatory bowel disease (IBD) development and progression. This research, therefore, aimed to evaluate whether there exists any relationship between nutrients and IBD. This case-control study from 2017 to 2019 was performed on 145 newly diagnosed IBD patients and 145 BMI-, sex-, and age-matched healthy controls who were recruited from a hospital clinic. A validated 168-item food frequency questionnaire was completed by each participant. Anthropometric measurements and physical activity levels were measured for all participants. Stata software was used to analyze all data. Of the 234 study individuals who participated, 112 were IBD patients and 122 were healthy people. The higher amount of seafood and cholesterol was related to an increased risk of IBD and ulcerative colitis development; however, individuals who had a higher intake of calcium were less likely to have Crohn's compared to the healthy group. There was a positive relation between honey and jam, seafood, organ meats, salt, fruits on trees, fruit juice, olives, and nuts and the probability of IBD, but there was a negative association between refined grains, potatoes, salty snacks, legumes, dairy, and cruciferous and the probability of IBD. Higher consumption of seafood and cholesterol was positively connected with a higher risk of IBD development in the current case-control study. A substantial association was seen between honey and jam, seafood, organmeats, salt, fruit on trees, fruit juice, olives, and nut consumption and IBD developement.

In this study we indicated that impaired serological responses to SARS-CoV-2 infection among patients with IBD, could have significant implications for this group of patients and should be considered in vaccination program.

In the phase III RESTORE‐IMI 2 study (ClinicalTrials.gov: NCT02493764), the combination antibacterial agent imipenem/cilastatin/relebactam (IMI/REL) demonstrated noninferiority to piperacillin/tazobactam for the end points of all‐cause mortality at day 28 and favorable clinical response at the early follow‐up visit in adult participants with gram‐negative hospital‐acquired bacterial pneumonia/ventilator‐associated bacterial pneumonia (HABP/VABP). Existing population pharmacokinetic models for imipenem (IPM) and REL were updated using data from patients with HABP/VABP from RESTORE‐IMI 2. Creatinine clearance (CrCl), body weight, infection type, and ventilation status were significant covariates in the updated model. The following simulations were performed to calculate the pharmacokinetic/pharmacodynamic joint probability of target attainment among patients with HABP/VABP and varying degrees of renal function: augmented renal clearance (CrCl ≥150 ml/min), normal renal function (CrCl ≥90 to

Selumetinib (AZD6244, ARRY-142886), a mitogen activated protein kinases (MEK1 and 2) inhibitor, has been granted orphan drug designation for differentiated thyroid cancer. The primary aim of this analysis was to characterize the population pharmacokinetics of selumetinib and its active metabolite N-desmethyl-selumetinib in patients with cancer. Concentration-time data from adult and pediatric clinical trials were pooled to develop a population pharmacokinetic model using a sequential approach where selumetinib and N-desmethyl-selumetinib data were modeled separately. A sequential zero- and first-order absorption with lag time with a two-compartment model for selumetinib and a two-compartment model for N-desmethyl-selumetinib best described the concentration-time data. Intrapatient variability in absorption was higher than interpatient variability. The apparent drug clearance (CL/F) from the central compartment was 13.5 L/hr (RSE 4.9%). Significant covariates for CL/F were age, alanine aminotransferase, and body surface area. This study confirms that flat dosing is appropriate in adults, whereas body-surface area based dosing should be used in pediatric patients.

Sunitinib malate is a small multi‐targeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet‐derived growth factor receptor (PDGFR) and stem cell factor receptor (KIT), which are highly expressed by some high‐grade brain tumors. We conducted a phase II study to estimate the efficacy and further characterize the pharmacokinetics of sunitinib in pediatric patients with recurrent or refractory high‐grade glioma (Stratum A) or ependymoma (Stratum B). This was a prospective, multicenter Phase II trial conducted through the Children's Oncology Group (ClinicalTrials.gov Identifier NCT01462695). Sunitinib, 15 mg/m2, was orally administered once daily for 4 weeks every 6 weeks. The safety and tolerability of sunitinib, an estimate of progression‐free survival (PFS), analyses of sunitinib pharmacokinetics (PK) and pharmacodynamics modulation of plasma VEGF and VEGFR2 were also assessed. Thirty eligible patients (17 patients on Stratum A, 13 patients on Stratum B) were enrolled and 29 patients were evaluable for response. Sunitinib was reasonably well tolerated in children with recurrent ependymoma or high‐grade glioma. Most adverse events were of mild‐to‐moderate severity and manageable with supportive treatment. While there was a statistically significant modulation of plasma VEGFR2 with sunitinib exposure, there were no sustained tumor responses. Both strata were closed at time of planned interim analysis as there was not sufficient efficacy associated with sunitinib in children with recurrent brain tumors. Sunitinib was well tolerated in children and young adults with recurrent high‐grade glioma or ependymoma but had no single agent objective antitumor activity in these patients.

Background Pegylated interferon α-2b (IFN α-2b) improves disease-free survival in adults with resected stage III melanoma. We conducted a study to determine the feasibility and safety of incorporating pegylated IFN α-2b as adjuvant therapy in the treatment of children and adolescents with high-risk melanoma. Pharmacokinetic studies of IFN α-2b and neuropsychological and quality of life (OL) assessments were performed. Patient and Methods Eligible patients with resected American Joint Committee on Cancer Stage IIC, IIIA, and IIIB cutaneous melanoma received nonpegylated IFN α-2b 20 million units/m2/day intravenously 5 days per week for 4 weeks (induction) followed by pegylated IFN α-2b 1 μg/kg/dose weekly subcutaneously (SQ) for 48 weeks (maintenance). Results Twenty-three patients (15 females, median age 10 years) were enrolled. All patients completed induction therapy; five patients did not complete maintenance therapy either because of recurrent disease (n = 2) or toxicity (n = 3). The most common grade 3 and 4 toxicities of pegylated IFN α-2b were neutropenia (35%) and elevated liver transaminases (17%). The median nonpegylated IFN α-2b AUC0-∞ (5,026 pcg⋅hr/ml) was similar to adults. The median pegylated IFN α-2b exposure (48,480 pcg⋅hr/ml) was greater than the cumulative weekly exposure for nonpegylated IFN α-2b administered SQ three times per week (TIW). Validated measures demonstrated an improvement in QOL scores and no decline in psychological functioning over the course of therapy. Conclusions Pegylated IFN α-2b 1 μg/kg/dose SQ weekly as maintenance therapy in children and adolescents with high-risk melanoma is feasible with tolerable toxicity and appears to yield higher exposures than nonpegylated IFN α-2b administered SQ TIW.

Objective To use micro-computed tomography (CT) to evaluate the fissure–fracture pattern in dogs affected by medial coronoid disease (MCD). Study Design Prospective case-controlled study. Sample Population Client owned (n = 21) and cadaver dogs (n = 5). Methods Segments were excised by subtotal coronoid ostectomy from dogs with MCD. Two categories were identified: fissured (Fi) or fractured (F). Three subcategories were contingent on fissure–fracture orientation: tip (T), radial incisure (RI), and radial incisure encroaching tip (RIT). Control segments were from nondiseased cadavers. High-resolution micro-CT (3 dimensional and 2 dimensional) was performed on all segments. Measurements included mean bone mineral density, trabecular number and thickness, and the angle of the fissure–fracture relative to the predominant trabecular orientation. Results A total of 28 diseased segments from 21 dogs (mean age 23.3 months, mean bodyweight 31.5 kg) were analyzed and categorized according to fissure–fragment location as Fi-T (n = 2), Fi-RIT (n = 2), Fi-RI (n = 3), F-T (n = 5), F-RIT (n = 9), F-RI (n = 7). The 3D analysis revealed subchondral micro-fracturing occurred in association with fragmentation. Canalicular impaction was associated with increase in trabecular number and decrease in trabecular space, most notably in RI categories. The 2D analysis showed that predominant trabecular orientation in control segments was significantly different to RI but not to T. The mean (SD) angle difference between the orientation of fissure–fracture and the predominant trabecular pattern was 6.9 (6.9)° for RI and 44.6 (49.6) ° for T. Conclusion T and RI fissure–fracture patterns show morphologic differences and likely arise from different supraphysiologic loading. Medial compartment disease is not homogenous and pattern recognition may assist further investigation of etiopathogenesis.

Background: Nowadays, there is an increasing interest in noninvasive methods to diagnose Helicobacter pylori infection. Indeed, they can profitably replace endoscopy in predicting the diagnosis. The stool antigen test for H. pylori is a noninvasive immunoassay to diagnose active infection with this bacterium in human fecal samples. The aim of this study was detection of alkyl hydroperoxide reductase protein (AhpC) antigen by immunoblotting in stool samples for diagnosis of H. pylori. Materials and Methods: Chromosomal DNA from H. pylori was isolated. AhpC gene was amplified by PCR, These amplicons were cloned into pTZ57R ⁄ T cloning vector then subcloned into pQE30 expression vector and overexpressed using isopropyl-beta-D-thiogalactopyranoside in E. coli M15. AhpC protein was purified by affinity chromatography. Rabbits were immunized with the purified AhpC protein for the production of antibodies. To determine the accuracy of the test for diagnosing H. pylori infection from stool, we evaluated 84 patients (6–81 years old) using Western blot analysis by rabbit anti-AhpC antibody. Positive rapid urease test on biopsy samples was considered as the gold standard. Results: AhpC gene was overexpressed, and AhpC protein was purified. Rabbit anti-AhpC antibody produced after immunization with the purified AhpC protein. By immunoblotting, we detected AhpC protein in the positive stool samples. The test showed a 83.3% sensitivity (95% CI: 69.8–92.5%) and a 91.7% specificity (95% CI: 77.5–98.2). Among the children, the sensitivity was 88.2% (95% CI: 63.6–98.5) and the specificity was 100% (95% CI: 69.2–100); in adults, the sensitivity and specificity were 80.6% (95% CI: 62.5–92.5) and 88.5% (95% CI: 69.8–97.6), respectively. Conclusions: Using of AhpC antigen for diagnosis of H. pylori infection is a useful noninvasive method, accurate in adolescents and children, and can be used for the development of a stool antigen detection kit for H. pylori. Helicobacter ISSN 1523-5378

Growth factors and nitric oxide (NO) play a major role in dysregulated immune response in ulcerative colitis (UC). Recent evidence has shown increased levels of transforming growth factor-beta(1) (TGF-beta(1)) in UC and suggested an anti-inflammatory effect for this factor. Based on our recent study, dysfunctional immunoregulation is present in saliva of UC patients, we hypothesized that salivary level of NO and TGF-beta(1) may differ by severity of UC and be useful to determine the activity of the disease. Thirty-seven UC patients and 15 healthy controls were enrolled and saliva samples were obtained. Truelove-Witts severity index and modified Truelove-Witts severity index were used to determine the severity of the disease. NO and TGF-beta(1) levels were detected in saliva of all patients and control subjects using enzyme-linked immunosorbent assay. A total of 21 patients had mild disease while 8 had moderate and 8 had severe colitis. Adjusted for baseline characteristics, the levels of NO and TGF-beta(1) in different groups were compared. Salivary NO and TGF-beta(1) levels were higher in UC patients comparing to controls (P < 0.00005 and P = 0.005, respectively). The levels of NO and TGF-beta(1) showed no significant differences among the severity groups (P = 0.46 and P = 0.23, respectively). NO levels linearly increased by age (Coeff = 1.5, r = 0.38, P = 0.02). Gender, extension of disease, and medical treatment did not affect NO and TGF-beta(1) levels. Although UC patients have abnormal amounts of NO and TGF-beta(1) in their saliva, their disease activity cannot be predicted by these factors, which may indicate a pathophysiologic role rather than being nonspecific inflammatory markers for TGF-beta(1) and NO.

Because of the claim that chronic cholestatic liver disease is associated with increased opioidergic tone and that lithium (Li+) inhibits physical dependency in morphine-dependent mice, the effects of chronic Li+ treatment on naloxone-precipitated withdrawal-like syndrome and antinociception were evaluated in an animal model of cholestasis. For this purpose, acute cholestasis was induced by bile duct ligation in mice. The treated group of mice was given lithium chloride (300 mg/l) as drinking fluid for 10–12 days before surgery and 5 days after surgery. Physical dependency was observed by precipitating an abstinence syndrome with naloxone (4 mg/kg, s.c.) 5 days after induction of cholestasis. Antinociception was assessed by tail-flick latency test in control and treated groups before administration of naloxone. Results of the present study revealed that chronic Li+ administration significantly reduced the withdrawal-like signs, whereas the antinociception assessed by tail-flick test was not observed in the control group of cholestatic mice. Serum Li+ level in this study was much lower than the commonly accepted therapeutic range. Lithium and opioid agonist ligands have diverse effects on transmembrane signal control systems. So the interaction of Li+ and opioid agonists observed in this study might also be through these systems. © 1998 John Wiley & Sons, Ltd.

Twenty-one women (age range 17-38 years) undergoing termination for social reasons in the first trimester were selected. Ultrasound determined the gestation and placental site. A commercially available flexible, sterile plastic tube was advanced to the level of the internal os. Five to eight millilitres of normal saline was injected and then gently aspirated into the tube. Chorionic villus sampling (CVS) or amniocentesis was subsequently performed for back-up sexing. Commercial X and Y probes were used simultaneously for fluorescence in situ hybridization (FISH) study of the cervical washing and back-up samples, XY signals were observed in 10 out of 12 male fetuses and 1 out of 4 female fetuses (false positive), indicating 81.3 per cent correct prediction. Four cervical washing samples did not provide enough cells for FISH. The frequency of cells showing XY signals varied from 3.6 to 47.8 per cent in male-predicted pregnancies. Placental-location, gestational age, or maternal age did not affect the successful retrieval of fetal cells. Trophoblast cells were obtained in a significant number (83 per cent) of pregnant women with male pregnancies by transcervical irrigation in the first trimester. This preliminary part of the study shows the presence of fetal cells in the transcervical samplings and the feasibility of FISH in detecting them; however, further studies are needed to isolate and purify fetal cells.

Purpose. The study was conducted to evaluate the effect of various degrees of fatty infiltration in patients with nonalcoholic fatty liver disease on hepatic artery resistance index and hepatic vein waveform patterns. Methods. After identification and grading of fatty infiltration, 60 patients and 20 normal healthy subjects were examined using color and spectral Doppler sonography. The level of fatty liver infiltration was ascertained and graded by biopsy in patients and excluded by MRI in controls. The patients were allocated to four study groups consecutively, until the required number was reached, according to infiltration level as follows: normal (group A), mild (group B), moderate (group C), and severe (group D). The hepatic vein waveforms were classified into the three following groups: triphasic, biphasic, and monophasic waveform. The hepatic artery resistance index was calculated as the mean of three different measurements. Results. The incidence of monophasic and biphasic hepatic vein waveform was 2 (10%) for group B, 11 (55%) for group C, 16 (80%) for group D, and none for group A. The difference in the distribution of triphasic Doppler waveform pattern between the patients and the control group was significant (p < 0.001). Hepatic artery resistance index was 0.81 (±0.02), 0.78 (±0.03), 0.73 (±0.03), and 0.68 (±0.05), respectively, in groups A, B, C, and D and was significantly different between groups (p < 0.001). Conclusion. As the severity of nonalcoholic fatty infiltration increases, the incidence of abnormal hepatic vein waveforms increases and hepatic artery resistance index decreases. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound 38:346-352, 2010

A new adsorbent, modified mesoporous lanthanum(III) silicate, has been prepared with various molar ratios of Si/La (10, 20, 40, 80) and cethyltrimethylammonium bromide (CTAB) as structure directing agent. XRD, nitrogen sorption, SEM, IR, thermogravimetry and sorption of radionuclides and toxic metal ions have been studied. The results show that adsorption amount of some element such as Pb(II) and Th(IV) has been increased significantly by incorporation of lanthanum ions in the framework of adsorbent. Separation of Co(II)-Th(IV), Co(II)-U(VI) and Mo(VI)-U(VI) has been developed on columns of this adsorbent.

Background Low-grade inflammation has been increasingly implicated in the pathophysiology of irritable bowel syndrome (IBS). Imbalances of pro- and anti-inflammatory cytokines and polymorphisms in cytokine genes have been reported in IBS; however, these findings have not been consistently observed. This may be due to small sample sizes and differences in ethnicities. Therefore, we performed a meta-analysis on the studies that investigated cytokine gene polymorphisms in IBS patients compared to healthy controls. Methods A PubMed and EMBASE search was performed, and cytokine gene polymorphisms, which had been investigated in at least two case-control studies, were evaluated. Pooled odds ratios (OR) for the genotypes were calculated using random- or fixed-effects models. Key Results Five studies that investigated interleukin-10 (IL-10; −1082 G/A), transforming growth factor-β1 (TGF-β1; +869 T/C and +915 G/C) and tumor necrosis factor (TNF; −308 G/A) polymorphisms in IBS patients and controls were included. High producer IL-10 (−1082 G/G; OR: 0.64 [95% CI: 0.48–0.87]) was significantly associated with a decreased risk of IBS. The intermediate producer TGF-β1 (+915 G/C) genotype showed a tendency toward decreasing the risk of IBS. No associations were found between TNF (−308 G/A) genotypes and IBS in the whole meta-analysis although an analysis of Asian studies revealed an association between TNF (−308 G/A and G/G) genotypes and IBS (OR: 0.50 [95% CI: 0.29–0.85]), and 1.82 [95% CI: 1.08–3.07], respectively). Conclusions & Inferences This meta-analysis indicates a role for IL-10 polymorphisms in IBS in general and TNF in Asian populations. Whether or not gene polymorphisms are associated with alterations in cytokine levels leading to functional effects at the level of the gut needs further investigation.