bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclic Vomiting: The Pattern and Syndrome Paradigm
Authors: Li B U.K.
Published: February 2024

Although it remains a mysterious disorder since its description over a century ago, cyclic vomiting syndrome appears to be more prevalent than previously thought. With the goal of improving detection of affected children, two quantitative historical criteria—peak intensity ≥ 4 emeses/h) and a episode frequency ≤ 9/ month—can differentiate those with an explosive, intermittent cyclic pattern from those with a low‐grade, daily chronic pattern. Diagnoses that can cause a cyclic vomiting pattern includes abdominal migraine, chronic sinusitis, intracranial neoplasm, anomalies of and mucosal injury to the gastrointestinal tract, urologic abnormalities, and metabolic and endocrine disorders. Because many organic disorders can mimic cyclic vomiting syndrome, a systematic diagnostic evaluation of potential underlying disorders is recommended. The following terminology is proposed: a cyclic pattern is differentiated from a chronic pattern of vomiting on the basis of a higher peak intensity of emesis and lower frequency of episodes; and of those with a cyclic vomiting pattern, an idiopathic subgroup who is not found to have an underlying disorder on diagnostic testing can be labeled as having cyclic vomiting syndrome.
Differential Diagnosis of Cyclic Vomiting Syndrome
Authors: Forbes David
Published: February 2024

Vomiting is a nonspecific symptom and cyclic vomiting is a symptom complex that may result from a disorder of any major organ system. Children with cyclic vomiting syndrome (CVS) need careful review and investigation at their earliest presentations to exclude potentially lethal abnormalities such as intestinal volvulus, metabolic disorders, and neurologic space‐occupying lesions. The range of abnormalities that may present with features consistent with CVS includes gastrointestinal obstructive, inflammatory and motility abnormalities, pancreatic disease, metabolic disease (particularly the amino acidopathies, organic acidurias, fatty acid oxidation defects, and acute intermittent porphyria), renal disease, epilepsy, migraine, and psychiatric disorders. Careful history taking will usually provide clues to these uncommon problems, but all children should undergo baseline assessment of gastrointestinal morphology and screening tests for renal and metabolic disease.
Probiotic Treatment Using Bifidobacterium lactis HN019 Reduces Weanling Diarrhea Associated With Rotavirus and Escherichia coli Infection in a Piglet Model
Authors: Shu Quan , Qu Freeman , Gill Harsharnjit S.
Published: February 2024

Background

Diarrhea associated with rotavirus and Escherichia coli is one of the major gastrointestinal problems faced by human infants. Using a piglet model, the authors investigated the protective effectiveness of probiotic feeding against naturally acquired diarrhea in weanlings.

Methods

Seventeen piglets were allocated into two groups balanced for live weight and litter of origin. The test group was administered Bifidobacterium lactis HN019 (109 colony‐forming units (cfu)/piglet/d) orally until the end of the experiment; the control group did not receive probiotic treatment. After 1 week, animals were penned individually and weaned onto a diet for a weaner. The degree of subsequent diarrheal disease was monitored in both groups of animals, feed intake and live weight gain of the piglets were assessed, and blood and fecal samples were collected to measure concurrent systemic and gastrointestinal tract immunologic activity.

Results

Compared with the controls, piglets that received B. lactis HN019 had a lower severity of weanling diarrhea and maintained a greater feed conversion efficiency during weaning. The protective effect of probiotic feeding was associated with lower concentrations of fecal rotavirus and E. coli, higher blood leukocyte phagocytic and T‐lymphocyte proliferative responses, and higher gastrointestinal tract pathogen‐specific antibody titers.

Conclusions

These results show that dietary treatment using B. lactis HN019 can reduce the severity of weanling diarrhea associated with rotavirus and E. coli, possibly via a mechanism of enhanced immune‐mediated protection. This study suggests that probiotic treatment may be an effective dietary means of preventing or limiting diarrhea in human infants.
The Effect of Cisapride on the Corrected QT Interval and QT Dispersion in Premature Infants
Authors: Cools Filip , Benatar Avram , Bougatef Adel , Vandenplas Yvan
Published: February 2024

Background

Cisapride is used frequently in premature neonates as a gastrointestinal prokinetic drug. Concerns exist, however, about its safety because of its effect on the QT interval. Premature infants could be at higher risk for side effects because of their immaturity. This prospective study investigated the pharmacokinetics of cisapride and its effects on corrected QT interval (QTc) and QT dispersion in premature infants.

Methods

Electrocardiogram examination was performed just before and after 72 hours of treatment with cisapride (0.2 mg/kg per dose, four times daily) in 10 premature infants. Trough and anticipated peak plasma level of cisapride and norcisapride were quantified after 72 hours of treatment. Results were compared with a cohort of 41 term infants aged 0 to 3 months receiving cisapride treatment.

Results

The QTc interval increased significantly from 423 ms to 461 ms after 72 hours of treatment (P = 0.0007). No effect was seen on QT dispersion (44.3 ms vs. 45.9 ms). The change in QTc interval was inversely related to postnatal age (R2 = 0.52;P = 0.02), whereas there was no correlation with gestational age or plasma levels of cisapride or norcisapride. Trough and anticipated peak plasma levels of cisapride and norcisapride were significantly higher in the premature infants compared with the term infants aged 0 to 3 months (P < 0.001).

Conclusions

Premature infants less than 1 month of age could be at higher risk for cardiac side effects of cisapride when used in the same dosage as in older infants. The daily dose should be reduced (0.1 mg/kg per dose, maximum four times daily), and the QTc interval should be monitored closely. The benefits and safety of cisapride in premature infants less than 1 month of age should be reconsidered.
Lansoprazole in Adolescents with Gastroesophageal Reflux Disease: Pharmacokinetics, Pharmacodynamics, Symptom Relief Efficacy, and Tolerability
Authors: Gunasekaran Thirumazhisai , Gupta Sandeep , Gremse David , Karol Michael , Pan Wei‐Jian , Chiu Yi‐Lin , Keith Roberta , Fitzgerald Joseph
Published: February 2024

Objectives:

To evaluate the pharmacokinetics, pharmacodynamics, symptom relief efficacy, and tolerability of lansoprazole in adolescents between 12 and 17 years of age with gastroesophageal reflux disease (GERD).

Methods:

Adolescents with symptomatic, endoscopically and/or histologically proven GERD were enrolled in this multicenter, double‐blind trial and randomized to lansoprazole 15 mg or 30 mg once daily for 5 days.

Results:

Sixty‐three adolescents were enrolled in the study. After lansoprazole administration, Tmax occurred at 1.6 hours in those treated with lansoprazole 15 mg and at 1.7 hours in those treated with lansoprazole 30 mg. Dose‐proportional increases in lansoprazole Cmax and AUC were observed in the treatment groups. Age, weight, and gender had no significant effect on Tmax, Cmax, or AUC. Lansoprazole produced significant increases (P ≤ 0.05) in mean 24‐hour intragastric pH and the percentages of time intragastric pH was above 3 and 4. The majority of adolescents treated with lansoprazole 15 mg (69%, 22/32) or lansoprazole 30 mg (74%, 23/31) demonstrated improvement in their reflux symptoms after 5 days of treatment. Adolescents in both dosage groups exhibited reductions from baseline in the percentage of days and nights with heartburn (or other predominant symptom of GERD), the severity of heartburn, the percentage of days antacids were used, and the number of antacid tablets used per day. Pharyngitis and headache were the most commonly reported side effects among adolescents treated with lansoprazole 15 mg and 30 mg, respectively. Five patients experienced adverse events considered to be possibly treatment‐related. One patient with a history of environmental allergies experienced a mild allergic reaction after 3 days of treatment with lansoprazole 15 mg. Among those treated with lansoprazole 30 mg, 4 patients each reported one occurrence of pain (toothache), diarrhea, dizziness, and rash.

Conclusion:

The pharmacokinetic parameters of lansoprazole observed in this study of adolescents are similar to those observed in studies of healthy adults. Lansoprazole 15 mg or 30 mg once daily for 5 days produces significant increases in intragastric pH, effectively relieves symptoms of reflux disease, and is well tolerated in adolescents with GERD.
Home‐Based Treatment of Malnourished Malawian Children with Locally Produced or Imported Ready‐to‐Use Food
Authors: Sandige Heidi , Ndekha MacDonald J. , Briend André , Ashorn Per , Manary Mark J.
Published: February 2024

Objectives:

To determine the efficacy of home‐based therapy with ready‐to‐use food (RTUF) in producing catch‐up growth in malnourished children and to compare locally produced RTUF with imported RTUF for this purpose.

Methods:

After a brief inpatient stabilization, 260 children with severe malnutrition were enrolled and systematically allocated to receive home therapy with either imported, commercially produced RTUF or locally produced RTUF. Each child received 730 kJ/kg/day and was followed up fortnightly. Children completed the study when they reached a weight‐for‐height Z score > −0.5 (WHZ), relapsed, died, or failed to achieve WHZ > −0.5 after 16 weeks. Analyses were stratified by human immunodeficiency virus (HIV) status.

Results:

78% of all children reached WHZ > −0.5, 95% of those with HIV‐negative status and 59% of those with HIV‐positive status. Eighty percent of those receiving locally produced RTUF and 75% of those receiving imported RTUF reached WHZ > −0.5. The difference between recovery rates was 5% (95% confidence interval [CI], −5–15%). The rate of weight gain was 0.4 g/kg/day (95% CI, −0.6, 1.4) greater among children receiving locally produced RTUF. The prevalence of diarrhea reported by mothers was 3.7% for locally produced RTUF and 4.3% for imported RTUF. After completion of home therapy and resumption of habitual diet for 6 months, 91% of all children maintained a normal WHZ.

Conclusions:

Home‐based therapy with RTUF was successful in affecting complete catch‐up growth. In this study, locally produced and imported RTUF were similar in efficacy in treating of severe childhood malnutrition.
Portal Hypertension and Duodenal Ulcer in Children
Authors: Hung Pei‐Yin , Ni Yen‐Hsuan , Hsu Hong‐Yuan , Chang Mei‐Hwei
Published: February 2024

Objectives:

The prevalence of duodenal ulcer (DU) in adult patients with portal hypertension is higher than in patients without portal hypertension. This study investigates the prevalence and characteristics of DU in children with portal hypertension.

Patients and Methods:

From January 1997 to December 2001, 80 children with portal hypertension who had undergone upper intestinal endoscopic examinations were enrolled. Possible factors contributing to the development of DU including severity of liver disease, portal hypertension, H. pylori, and serum gastrin level were studied. The control group consisted of 80 age‐and sex‐matched children with gastrointestinal symptoms but no liver disease and who underwent endoscopic examination during the same period.

Results:

The prevalence of DU was significantly higher in children with portal hypertension than in children with digestive symptoms only (22.5%v 8.8%; P =0.017). DU was more common and appeared earlier in children with a history of variceal bleeding. The presence of DU was independent of the severity of liver disease, H. pylori infection and serum gastrin level.

Conclusion:

DU occurs commonly in children with portal hypertension, especially in those who have had variceal bleeding. It is mandatory to screen a patient with gastrointestinal bleeding for DU even in the presence of esophageal varices. Elevated portal pressure might be a factor contributing to the development of DU.
Glucoamylase Activity in Infants and Children: Normal Values and Relationship to Symptoms and Histological Findings
Authors: Lee P. C. , Werlin Steven , Trost Beth , Struve Mark
Published: February 2024

Background:

Starch digestion is dependent on a combination of pancreatic and salivary amylase and the intestinal brush border enzymes glucoamylase and sucrase‐isomaltase. Glucoamylase splits successive glucose molecules from the nonreducing end of starch molecules and is particularly important in infants who are relatively deficient in pancreatic amylase.

Methods:

The authors measured glucoamylase activity in endoscopic mucosal biopsies submitted for measurement of disaccharidase activity from 214 patients aged 1 month to 20 years. Glucoamylase activity was measured using glucose polymers (polycose) as the substrate. The authors also related enzyme activity to histologic appearance and clinical indication for endoscopy.

Results:

The most common reasons for biopsy were abdominal pain, gastroesophageal reflux, and vomiting. Disaccharidase activity by age was similar to previous reports. Glucoamylase activity did not differ with age, but was 2 to 3 times the activity reported previously. Glucoamylase activity was significantly depressed in children with the most severe histologic abnormalities. Normal glucoamylase activity (±2 SD) was 80.6 ± 54.8 μmoles of glucose produced per minute per gram of protein.

Conclusions:

Glucoamylase activity is 2 to 3 times higher when glucose polymers are used as substrate than when glycogen is used. Severe mucosal disease is associated with reduced glucoamylase activity. Quantitation of glucoamylase activity with glucose polymers is more appropriate in evaluating children since these polymers are commonly used as carbohydrate source in the diet.
Esophagitis: Optimizing Diagnostic Yield by Biopsy Orientation
Authors: Brindley Nicola , Sloan J. M. , McCallion W. A.
Published: February 2024

Objectives:

There is poor correlation between gastroesophageal reflux (GER) symptoms, intraesophageal pH monitoring and endoscopic or histologic appraisal of esophagitis in the pediatric age group. To optimize the diagnosis of childhood esophagitis, histologic evaluation of esophageal pinch and suction biopsies after orientation were compared.

Methods:

Thirty consecutive children with GER, age range 6 months to 7 years, were prospectively evaluated with upper gastrointestinal endoscopy and biopsy. Three pinch biopsies and one suction biopsy were examined after different methods of biopsy orientation. The suction biopsy orientated with ×10 magnification represented the standard against which the pinch biopsies were compared.

Results:

After suction biopsy with tissue orientation using ×10 magnification 90% of biopsies were adequate for histologic appraisal. Ninety‐three percent of esophageal pinch biopsies orientated with ×10 magnification were adequate for analysis. After pinch biopsy orientated without magnification 90% of biopsies were suitable for histologic appraisal. Finally, in the pinch biopsy group without formal orientation, only 63% of the biopsies were adequate for histologic analysis and diagnosis of esophagitis.

Conclusion:

Orientation of esophageal pinch biopsies improves histologic appraisal and hence increases the diagnostic yield of esophagitis in children with GER. The tissue fragments can be easily orientated in the endoscopy room before placement in fixative.
Regulatory Regions in the Rat Lactase‐Phlorizin Hydrolase Gene that Control Cell‐Specific Expression
Authors: Verhave Menno , Krasinski Stephen D. , Christian Sara I. , Van Schaik Sandrijn , van Den Brink Gijs R. , Doting Edwina M. H. , Maas Saskia M. , Wolthers Katja C. , Grand Richard J. , Montgomery Robert K.
Published: February 2024

Objectives:

Lactase‐phlorizin hydrolase (LPH) is an enterocyte‐specific gene whose expression has been well‐characterized, not only developmentally but also along the crypt‐villus axis and along the length of the small bowel. Previous studies from the authors’ laboratory have demonstrated that 2 kb of the 5′‐flanking region of the rat LPH gene control the correct tissue, cell, and crypt‐villus expression in transgenic animals.

Methods:

To examine further the regulation conferred by this region, protein‐DNA interactions were studied using DNase I footprint analyses in LPH‐expressing and nonexpressing cell lines. Functional delineation of this 5′‐flanking sequence was performed using deletion analysis in transient transfection assays.

Results:

Studies revealed a generally positive activity between −74 and −37 bp, a cell‐specific negative region between −210 and −95 bp, and additional elements further toward the 5′ terminus that conferred a highly cell‐specific response in reporter activity. Computer analysis of distal regions encompassing identified footprints revealed potential binding sites for various intestinal transcription factors. Co‐transfection and electromobility shift assay experiments indicated binding of HNF3β at three sites relevant to LPH expression.

Conclusions:

The data demonstrate that the cell specificity of LPH gene expression depends upon both positive and negative interactions among elements in the first 2 kb of the LPH 5′‐flanking region.
Clinical Usefulness of Culturing H. Pylori from Gastric Juice in Patients with Severe Neurological Impairment
Authors: Yamazaki Tsutomu , Inoue Miyuki , Sasaki Nozomu , Yamada Kazutaka , Minamide Wakio , Matsumoto Takaaki
Published: February 2024

Objectives:

To clarify the diagnostic usefulness of culturing Helicobacter pylori from gastric juice for the diagnosis of H. pylori infection in patients with neurologic impairment.

Methods:

Seventy‐five patients (44 males, 31 females) with severe neurologic impairment admitted to Tokyo Children's Rehabilitation Hospital were included in this study. Samples of gastric juice obtained from these patients were put into Helicoporter™, a transport medium for H. pylori. Samples were then centrifuged and sediment was inoculated onto a culture medium. Polymerase chain reaction assays were performed on 41 gastric juice samples for comparison with results of culture. Tests for occult blood in gastric juice and serum anti‐H. pylori immunoglobulin G were tested for all patients.

Results:

H. pylori was isolated from 33 of 75 gastric juice samples by culture (positive rate, 44%). There was agreement between results of culture and polymerase chain reaction assays in 38 samples (93%). Twenty‐two samples were positive and 16 were negative by both methods. In H. pylori immunoglobulin G‐positive patients, occult blood was more frequently found in the culture‐positive group (92%) than in the culture‐negative group (59%) (P <0.025). The rate of detection of occult blood in immunoglobulin G‐negative patients was similar in the culture‐positive group (44%) and culture‐negative group (50%).

Conclusions:

The combination of a culture method using gastric juice and a serum H. pylori immunoglobulin G assay was not invasive and clinically useful for evaluating H. pylori infections among handicapped patients.
Depressive Symptoms and Inflammatory Bowel Disease in Children and Adolescents: A Cross‐Sectional Study
Authors: Szigethy Eva , Levy‐Warren Anna , Whitton Sarah , Bousvaros Athos , Gauvreau Kimberlee , Leichtner Alan M. , Beardslee William R.
Published: February 2024

Objectives:

This study assessed the rates of depressive symptoms in older children and adolescents with inflammatory bowel disease (IBD) and the associations between depressive symptoms and IBD disease characteristics.

Methods:

One hundred and two youths (aged 11–17 years) with IBD seen consecutively in a gastroenterology clinic were screened for depressive symptoms using the Children's Depression Inventory (CDI). Subjects with CDI scores ≥12 were evaluated for current psychiatric diagnoses using the Schedule for Affective Disorders and Schizophrenia for School‐Age Children—Present and Lifetime Version (K‐SADS‐PL). Disease characteristics examined included IBD type, duration, current severity, course, age at diagnosis and steroid treatment.

Results:

Of the total sample, 25 (24.5%) had a CDI score ≥12, consistent with clinically significant depressive symptoms. Nineteen of 25 qualified subjects participated in the K‐SADS‐PL semi‐structured interview and 16 of 19 met criteria for major or minor depressive disorder. Mean CDI scores positively correlated with age at IBD diagnosis but not with IBD type, duration or course. Youths with moderate/severe current IBD‐related symptoms had significantly higher mean CDI scores than those with inactive disease activity. Anhedonia, fatigue and decreased appetite were selectively correlated with IBD disease severity. Subjects on steroids were more likely to have CDI scores ≥12, and those with such scores were on higher doses of steroids than subjects without clinically significant depressive symptoms (both P values < 0.05).

Conclusions:

These findings support the recommendation that adolescents with IBD in outpatient medical care settings, particularly older adolescents and those on steroids, should be screened for depression.
Cow's Milk Allergy in Infants with Atopic Eczema is Associated with Aberrant Production of Interleukin‐4 During Oral Cow's Milk Challenge
Authors: Rautava Samuli , Isolauri Erika
Published: February 2024

Objectives:

A failure in the establishment and maintenance of oral tolerance in infancy may result in food allergy. To further assess the role of the intestinal immune system in cow's milk allergy (CMA), we investigated the systemic production of the pro‐allergenic Th2 cytokine interleukin (IL)‐4 and antiallergenic cytokines IL‐10, transforming growth factor (TGF)‐β1 and TGF‐β2 in infants suffering from atopic eczema with and without CMA during antigen elimination diet and oral antigen exposure.

Methods:

18 infants (mean age, 9.6 months; 95% confidence interval 8.1‐11.1 months) with atopic eczema and CMA and 17 infants (mean age, 9.7 months; 95% confidence interval 8.6‐10.9 months) with atopic eczema tolerant to milk as assessed by a double blind, placebo‐controlled cow's milk challenge were investigated. Peripheral blood mononuclear cells were obtained during antigen elimination diet and during oral cow's milk challenge and stimulated with Concanavalin‐A or cow's milk or were left unstimulated. The cytokine concentrations were measured by enzyme‐linked immunosorbent assay.

Results:

During antigen elimination, the Concanavalin A‐stimulated production of TGF‐β2 was significantly lower in infants with CMA as compared with infants without CMA: 129 pg/mL (interquartile ratio, 124‐144 pg/mL) vs. 149 pg/mL (interquartile ratio, 133‐169 pg/mL); P = 0.016. During oral antigen exposure, the immune responses in infants with CMA were characterized by significantly higher spontaneous production of IL‐4 as compared with those without CMA: 12.0 pg/mL (interquartile ratio, 5.2‐28.3 pg/mL) vs. 4.2 pg/mL (interquartile ratio, 1.5‐7.6 pg/mL); P = 0.018.

Conclusions:

Infants with atopic eczema and CMA exhibit markedly increased systemic pro‐allergenic IL‐4 responses on intestinal antigen contact, which may partially be explained by a defective ability to launch anti‐allergenic TGF‐β2 responses.
Oral Vitamin A, E and D Supplementation of Pre‐Term Newborns either Breast‐Fed or Formula‐Fed: a 3‐Month Longitudinal Study
Authors: Delvin Edgard E. , Salle Bernard L. , Claris Olivier , Putet Guy , Hascoet Jean‐Michel , Desnoulez Laure , Messai Sam , Lévy Émile
Published: February 2024

Background:

In contrast to the studies of vitamin A and E status in children, adolescents and adults, information on preterm infants is scarce. In the present investigation we examined the vitamin A, D and E status of pre‐term infants at birth, and verified whether, at 1 and 3 months, breast or formula feeding affected the plasma concentration of those vitamins while being supplemented with Uvesterol ADEC.

Patients and Methods:

In this prospective study, 2 groups of consecutively recruited preterm newborns fed either breast milk or formula received 3000 IU of vitamin A, 5 IU of vitamin E and 1000 IU of vitamin D daily. Vitamin A and E were measured by high performance liquid chromatography and spectrophotometry. 25‐hydroxyvitamin D, a surrogate marker for vitamin D status, was measured by radioimmunoassay, and retinol binding‐protein concentration was measured by immunonephelometry.

Results:

At birth, formula‐fed and breast‐milk fed infants had similar plasma concentrations of vitamin A (0.75 ± 0.20 and 0.64 ± 0.21 m mol/L, ns), 25‐hydroxyvitamin D (34.4 ± 25.6 and 47.5 ± 26.7 nmol/L, ns) and vitamin E (9.5 ± 3.2 and 8.4 ± 3.3 μmol/L, ns). Vitamins A and E, and retinol binding‐protein concentrations steadily increased with time in both groups of infants without attaining, at 3 months, values considered normal in term infants and in young children. At 3 months of age, concentrations of 25‐hydroxyvitamin D reached values comparable to those observed in term infants.

Conclusion:

Plasma concentrations of vitamins A and E and of retinol binding‐protein steadily increased during the the study without reaching full repletion values. At the conclusion of the study, the type of nutrition did not affect plasma vitamin concentrations.
Removal of Metabolites, Cytokines and Hepatic Growth Factors by Extracorporeal Liver Support in Children
Authors: Auth Marcus KH. , Kim Hyun Soo , Beste Mechthild , Bonzel Klaus E. , Baumann Ulrich , Ballauff Antje , Wallot Michael , Borchers Tanja , Vester Udo , Grasemann Corinna , Hauffa Berthold , Hoyer Peter F. , Gerken Guido , Voit Thomas
Published: February 2024

Background:

Molecular Adsorbents Recirculating System (MARS)‐mini has recently been approved and applied in children with hepatic failure. However, its indication, efficacy and capability to induce liver regeneration remain unclear. The aim of our pilot study in children was to analyse the impact of MARS on markers of detoxification and regeneration.

Methods:

In children with fulminant Wilson's disease and bridged with MARSmini for liver transplantation, we analyzed toxic metabolites (bile acids, bilirubin, lactate, ammonia, tryptophan and copper), regulators of the inflammatory cascade [nitrate, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), methionine, cystine and hyaluronic acid] and hepatic growth factors [hepatocyte growth factor (HGF), epidermal growth factor (EGF), transforming growth factor‐β1 (TGF‐β1), cortisol, corticosteroid‐binding globulin (CBG), insulin‐like growth factor‐1 (IGF‐1), angiogenin, vascular endothelial growth factor (VEGF), IL‐6 and TNF‐α] from blood, albumin circuit and haemodialysate from four applications.

Results:

In all four applications, transfer of toxic metabolites (6/6) and inflammatory mediators (6/6), but also of hepatic growth factors (9/10), into the albumin circuit of MARS was consistently detected. Corresponding blood levels were decreased for 3/6 metabolites, 3/6 inflammatory mediators and 1/10 growth factors and increased for 1/10 growth factors. Bridging for liver transplantation was successful with MARS.

Conclusions:

In our prospective study, substantial extraction of albumin‐bound and water‐soluble candidate substances was detected with variable effect on respective blood levels. Notably, essential factors inducing liver regeneration were simultaneously removed. These data provide a basis for evaluation of liver restoration and efficacy of liver support in children with liver failure to devise a collaborative, multicentre trial.
Is There A Role for Pre‐, Pro‐ and Synbiotics in the Treatment of Functional Constipation in Children? A Systematic Review
Authors: Koppen Ilan J.N. , Benninga Marc A. , Tabbers Merit M.
Published: February 2024

Purpose of review:

To investigate the efficacy and safety of pre‐, pro‐ and synbiotics in the treatment of pediatric functional constipation (FC).

Recent findings:

A recent study reported that the gut microbiota in obese children with FC differs from that of obese children without FC. The gut microbiota may be involved in the pathophysiology of FC. Pre‐ and probiotics have been suggested as potential treatment modalities for FC in children.

PubMed and Cochrane databases were searched from inception to February 2016. We found 6 RCTs on prebiotics, 6 RCTs on probiotics and 1 RCT concerning synbiotics. Overall, most studies were at high risk of bias. The majority of studies were unable to demonstrate a significant effect of pre‐, pro‐ or synbiotics on predefined outcome measures such as defecation frequency, fecal incontinence and painful or difficult defecation. Pre‐, pro‐ and synbiotics were not associated with significant adverse effects. In conclusion, there is insufficient evidence to recommend pre‐, pro‐ or synbiotics in the treatment of children with functional constipation. High‐quality randomized controlled trials are warranted to further explore these treatment modalities.
Evaluation and control of energy‐efficient processes for separating epichlorohydrin‐oriented quaternary system
Authors: Qi Fuqiang , Yang Junling , Zhang Zhentao , Wu Zhenqun , Ren Qiyue , Zhang Huafu , Li Yanan , Zhang Yu
Published: February 2024

BACKGROUND

The direct epoxidation of allyl chloride is a clean and efficient synthesis method for producing epichlorohydrin (ECH), which is a crucial organic intermediate widely used in the fields of renewable energy and aerospace. However, the presence of multiple azeotropes in the synthesized product using this method complicates the separation process and results in high energy consumption. To efficiently separate high‐purity ECH, this paper investigates and analyzes three separation schemes based on phase‐equilibrium analysis: hybrid extractive distillation (HED), pressure swing distillation (PSD) and three‐column batch distillation (TCBD).

RESULTS

The operating parameters of the three separation processes are optimized by the sequential iterative optimization method such that the minimum total annual cost can reach $493 491 yr−1. The thermal integration method is used for process energy‐saving optimization, and the total annual cost can be further reduced by 6.9%. In addition, a comprehensive evaluation based on economic, energy, environmental and exergy analysis is conducted, and reveals that the TCBD process with thermal integration is optimal. A control structure is designed for the TCBD process to enhance its robustness such that the purity of ECH remains above 99.9 mol% under ±10% disturbances in feed flowrate and composition.

CONCLUSIONS

Compared with the HED and PSD processes, the TCBD process has better economic and environmental benefits, and its control structure can effectively resist disturbances. It is reasonable to believe that the TCBD process can be an excellent solution for the industrial production of ECH. © 2024 Society of Chemical Industry (SCI).
Transfer of inflammatory mitochondria via extracellular vesicles from M1 macrophages induces ferroptosis of pancreatic beta cells in acute pancreatitis
Authors: Gao Yuhua , Mi Ningning , Wu Wenxiang , Zhao Yuxuan , Fan Fangzhou , Liao Wangwei , Ming Yongliang , Guan Weijun , Bai Chunyu
Published: February 2024

Extracellular vesicles (EVs) exert a significant influence not only on the pathogenesis of diseases but also on their therapeutic interventions, contingent upon the variances observed in their originating cells. Mitochondria can be transported between cells via EVs to promote pathological changes. In this study, we found that EVs derived from M1 macrophages (M1‐EVs), which encapsulate inflammatory mitochondria, can penetrate pancreatic beta cells. Inflammatory mitochondria fuse with the mitochondria of pancreatic beta cells, resulting in lipid peroxidation and mitochondrial disruption. Furthermore, fragments of mitochondrial DNA (mtDNA) are released into the cytosol, activating the STING pathway and ultimately inducing apoptosis. The potential of adipose‐derived stem cell (ADSC)‐released EVs in suppressing M1 macrophage reactions shows promise. Subsequently, ADSC‐EVs were utilized and modified with an F4/80 antibody to specifically target macrophages, aiming to treat ferroptosis of pancreatic beta cells in vivo. In summary, our data further demonstrate that EVs secreted from M1 phenotype macrophages play major roles in beta cell ferroptosis, and the modified ADSC‐EVs exhibit considerable potential for development as a vehicle for targeted delivery to macrophages.
Allogeneic stem cell transplant recipients surviving at least 2 years without relapse: outcome and risk factors
Authors: Grønvold B. Linder , Ali Maryan Mohamed , Myklebust Tor Å , Lenartova Andrea , Remberger Mats , Abrahamsen Ingerid Weum , Tjønnfjord Geir Erland , Myhre Anders Eivind , Fløisand Yngvar , Gedde‐Dahl Tobias
Published: February 2024

Outcomes of 2‐year survivours undergoing allo‐haematopoietic stem cell transplantation at Oslo University Hospital were retrospectively assessed with the objectives of identification of risk factors for late death as possible means for precautionary measures and interventions to improve long‐term survival.

421 patients with haematological malignancy, transplanted between 2005 and 2019, alive and free of disease after 2 years were included with data reported from The OUS‐HSCT registry. Median follow‐up was 6.2 years (2.016.1), and 232 patients (55%) were observed for minimum 5 years.

The probability of being alive 5 and 10 years after HSCT was 86% and 76%. Primary risk factors for late death included initial diagnosis of age ≥ 60 years, chronic lymphocytic leukaemia (CLL), previous blood stream‐ or invasive fungal infection (BSI, IFI), and chronic graft‐versus‐host disease (cGVHD). Transplant‐related mortality (TRM) and relapse at 5 years were 9.0% and 7.7%, respectively. Two factors were associated with the latter: cytomegalovirus (CMV) seronegative donor and CLL. Compared with the age‐ and gender‐matched Norwegian general population, life expectancy was lower for each disease, except for CML.

The prospect for the long‐term survival is good for 2‐year survivors of the allogeneic hematopoietic stem cell transplantation. However, life expectancy remains inferior to the age‐ and gender‐matched general population. Optimising prophylaxis and treatment for chronic GVHD, BSI and IFI are needed along with the improved adherence to guidelines for early detection of secondary malignancies. Measures to improve immune reconstitution, possibly the microbiota, and the use of CMV seropositive donors regardless of recipient sero‐status may be warranted and should be addressed in further studies.
Panicolytic‐like effects of environment enrichment on male mice threatened by Bothrops jararaca lancehead pit vipers
Authors: de Paula Rodrigues Bruno Mangili , Falconi‐Sobrinho Luiz Luciano , de Campos Alline Cristina , Kanashiro Alexandre , Coimbra Norberto Cysne
Published: February 2024

Environment enrichment (EE) is a well‐known eustress model showing beneficial effects in different psychiatric diseases, but its positive properties in panic disorders are not yet established. The confrontation between prey and predator in complex arenas has been validated as a putative panic attack model. The principal aim of this work was to investigate the role of the EE on panic‐like defensive responses elicited by mice threatened by venomous snakes. After 6 weeks of exposure either to an enriched or standard environments, 36 male mice were habituated in a complex polygonal arena for snakes containing an artificial burrow and elevated platforms for escape. The animals were confronted by Bothrops jararaca for 5 min, and the following antipredatory responses were recorded: defensive attention, stretched attend posture, flat back approach, prey versus predator interaction, oriented escape behavior, time spent in a safe place, and number of crossings. Mice threatened by snakes displayed several antipredatory reactions as compared to the exploratory behavior of those animals submitted to a nonthreatening situation (toy snake) in the same environment. Notably, EE causes anxiolytic‐ and panicolytic‐like effects significantly decreasing the defensive attention and time spent in safe places and significantly increasing both prey versus predator interaction and exploratory behavior. In conclusion, our data demonstrate that EE can alter the processing of fear modulation regarding both anxiety‐ and panic‐like responses in a dangerous condition, significantly modifying the decision‐making defensive strategy.
Isotopic effect of oxygen on the Raman mapping of a polycrystalline uranium dioxide UO2
Authors: Gaillard Clotilde , Sarrasin Lola , Panetier Clémentine , Pipon Yves , Ducher Roland , Moncoffre Nathalie
Published: February 2024

Uranium dioxide (UO2) is a widely studied material due to its use as fuel in pressurised water reactors (PWR), and Raman spectroscopy is a technique of choice to characterise the evolution of its microstructure. UO2 crystallises in a fluorite CaF2 (space group Fm‐3m) structure that gives rise to a unique Raman signature, the T2g band. However, several other bands are often detected whose attribution remains unclear. The present study gives new insights on the Raman spectrum of UO2 thanks to the combination of isotopic labelling with 18O and Raman imaging. In addition to the expected T2g, U2 (LO), 2LO and U3 bands, we have detected a doublet at 885 and 925 cm−1, a U* band at 555 cm−1 in some specific areas and two bands located at 367 and 1196 cm−1. All Raman bands shift under the effect of the replacement of 16O by 18O, excepting for the U* band that could not be detected anymore. The isotopic shift ratio could be determined for 20% and 30% 18O labelling. No discrepancy in band position is observed between grains and grain boundaries, except for the U2(LO) band. We also evidence a difference between the U defect bands and the 885 and 925 cm−1 doublet bands evolution under labelling, although the latter also seems to be connected to the presence of defects in the material.
Bayesian meta‐analysis for evaluating treatment effectiveness in biomarker subgroups using trials of mixed patient populations
Authors: Wheaton Lorna , Jackson Dan , Bujkiewicz Sylwia
Published: February 2024

During drug development, evidence can emerge to suggest a treatment is more effective in a specific patient subgroup. Whilst early trials may be conducted in biomarker‐mixed populations, later trials are more likely to enroll biomarker‐positive patients alone, thus leading to trials of the same treatment investigated in different populations. When conducting a meta‐analysis, a conservative approach would be to combine only trials conducted in the biomarker‐positive subgroup. However, this discards potentially useful information on treatment effects in the biomarker‐positive subgroup concealed within observed treatment effects in biomarker‐mixed populations. We extend standard random‐effects meta‐analysis to combine treatment effects obtained from trials with different populations to estimate pooled treatment effects in a biomarker subgroup of interest. The model assumes a systematic difference in treatment effects between biomarker‐positive and biomarker‐negative subgroups, which is estimated from trials which report either or both treatment effects. The systematic difference and proportion of biomarker‐negative patients in biomarker‐mixed studies are used to interpolate treatment effects in the biomarker‐positive subgroup from observed treatment effects in the biomarker‐mixed population. The developed methods are applied to an illustrative example in metastatic colorectal cancer and evaluated in a simulation study. In the example, the developed method improved precision of the pooled treatment effect estimate compared with standard random‐effects meta‐analysis of trials investigating only biomarker‐positive patients. The simulation study confirmed that when the systematic difference in treatment effects between biomarker subgroups is not very large, the developed method can improve precision of estimation of pooled treatment effects while maintaining low bias.
Creating value through diversity: Analysis of the strategic management of BoD diversity in favor of sustainable performance
Authors: Paolone Francesco , Bifulco Giuseppe Maria , del Mar Perona Alfageme María
Published: February 2024

In this article, we explore the impact of the characteristics of the Board of Directors (BoD) on environmental, social, and governance (ESG) performance for European listed companies and its evolution during the period 2018/2021. The purpose of this study is to understand if and how the BoD characteristics influence the ESG performance of the major listed companies in the EU before and after the COVID‐19 breakthrough. The COVID‐19 pandemic is taken as a reference point in time, considering that several studies show that, even in a health crisis with economic repercussions for the whole world, companies have continued to increase their commitment to ESG practices. The sample is composed of 600 European listed companies and covers the period from 2018 to 2021. The ESG score and the other variables are collected for all companies included in the STOXX 600 index (from the Refinitiv Workspace database) and analyzed using the ordinary least square (OLS) panel regression analysis at country and industry level covering the period 2018–2021. The results of our analysis show no significant relationship between BoD characteristics (in terms of gender diversity, cultural diversity, and special skills) and ESG performance in the pre‐COVID‐19 era. In the post‐COVID‐19 era, gender diversity is the only characteristic of the BoD, among those investigated, capable of influencing nonfinancial performance. This result, in line with the resource density theory, is justified by the increase in the average number of women in the BoD in the two‐year period 2020–2021 compared to the previous one (2018–2019). We offer theoretical and practical implications to enhance ESG performance by combining BoD characteristics. We finally contribute to enhance the debate on the relevance of the BoD characteristics and ESG performance relationship providing consistent findings to emphasize the quality of the BoD for the ESG reporting and performance.
Feasibility assessment of a low‐cost visible spectroscopy‐based prototype for monitoring polyphenol extraction in fermenting musts
Authors: Alfieri Gianmarco , Modesti Margherita , Bellincontro Andrea , Renzi Francesco , Aleixandre‐Tudo Jose Luis
Published: February 2024

BACKGROUND

Polyphenols have long been used to evaluate grape and wine quality and it is necessary to measure them throughout various winemaking stages. They are currently assessed predominantly through analytical methods, which are characterized by time‐consuming procedures and environmentally harmful practices. Non‐destructive spectroscopy‐based devices offer an alternative but they tend to be costly and not readily accessible for smaller wineries. This study introduces the initial steps in employing a portable, user‐friendly, and cost‐effective visible (VIS) spectrophotometer prototype for direct polyphenol measurement during winemaking.

RESULTS

Grapes (cv Syrah, Bobal, and Cabernet Sauvignon) at different maturation stages were fermented with or without stems. Throughout fermentation, parameters such as color intensity, total polyphenol index, total anthocyanins, and tannins were monitored. Concurrently, VIS spectra were acquired using both the prototype and a commercial instrument. Chemometric approaches were then applied to establish correlation models between spectra and destructive analyses. The prototype models demonstrated an acceptable level of confidence for only a few parameters, indicating their lack of complete reliability at this stage.

CONCLUSIONS

Visible spectroscopy is already utilized for polyphenol analysis in winemaking but the aspiration to automate the process in wineries, particularly with low‐cost devices, remains unrealized. This study investigates the feasibility of a low‐cost and user‐friendly spectrophotometer. The results indicate that, in the early stages of prototype utilization, the goal is attainable but requires further development and in‐depth assessments. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Bioactivity and molecular docking studies of selected plant compounds
Authors: Alimi Dhouha , Hraoui Manel , Hajri Azhar , Taamalli Wael , Selmi Slimen , Sebai Hichem
Published: February 2024

BACKGROUND

The shortcomings of synthetic pesticides are becoming increasingly evident. In the pursuit of looking for alternative, environmentally friendly pesticides, the potential use of two naturally occurring sesquiterpenes, α‐bisabolol and bisabolol oxide A, as bactericides or acaricides, was investigated against three gram‐positive and three gram‐negative bacteria, and the eggs and larvae of the cattle tick Hyalomma scupense, respectively. The primary targeted site of synthetic insecticides is acetylcholinesterase (AChE), so the inhibitory activity of both sesquiterpenes was evaluated. Then, molecular docking and molecular mechanics generalized Born surface area (MM‐GBSA) studies were performed to gain insight into their binding mode in the AChE active site.

RESULTS

Bisabolol oxide A showed good activity against Staphylococcus aureus, Escherichia coli, and Salmonella enteritidis with inhibition zones ranging from 16 to 34 mm and minimal inhibitory concentration (CIM) of 3.125  mg mL−1. Ovicidal and larvicidal assays revealed promising activity of α‐bisabolol and bisabolol oxide A against H. scupense, with bisabolol oxide A being more effective against larval ticks with lethal concentration (LC50) value of 0.78%. Both compounds also displayed potent anti‐AChE activity with inhibition concentration (IC50) values of 37.09 and 28.14 μg mL−1, respectively. Furthermore, α‐bisabolol and bisabolol oxide A exhibited good and comparable docking scores (−7.289 and −7.139 Kcal mol−1, respectively) and were found to accommodate in the active‐site gorge of AChE via hydrogen bonding and hydrophobic interactions.

CONCLUSION

Bisabolol oxide A and, to a lesser degree, α‐bisabolol are active against bacteria and ectoparasites and may represent an economical and sustainable alternative to toxic synthetic pesticides to control pathogens. © 2024 Society of Chemical Industry.