bluuebunny/crossref_metadata_2025 huggingface dataset:
Left ventricular hypertrophy as a risk factor for accelerated brain aging: Results from the Study of Health in Pomerania
Authors: Frenzel Stefan , Bülow Robin , Dörr Marcus , Felix Stephan B. , Friedrich Nele , Völzke Henry , Wittfeld Katharina , Grabe Hans J. , Bahls Martin
Published: February 2024

Previous studies provided evidence for the importance of cardiac structure abnormalities, in particular greater left ventricular (LV) mass, for brain aging, but longitudinal studies are lacking to date. We included 926 individuals (median age 48 years; 53% women) from the TREND cohort of the Study of Health in Pomerania (SHIP) without reduced ejection fraction or a history of myocardial infarction. LV mass index (LVMI) was determined by echocardiography at baseline. Brain morphometric measurements were derived from magnetic resonance images at baseline and 7‐year follow‐up. Direct effects of baseline LVMI on brain morphometry at follow‐up were estimated using linear regression models with adjustment for baseline brain morphometry. At baseline, median LVMI was 40 g/m2.7 and 241 individuals (26%) met the criterion of LV hypertrophy. After correction for multiple testing, baseline LVMI was directly associated with reduced global cortical thickness and increased cortical brain age at follow‐up independent from hypertension and blood pressure. Exposure‐outcome relations were nonlinear and significantly stronger in the upper half of the exposure distribution. Specifically, an increase in baseline LVMI from the 50% quantile to the 95% quantile was associated additional 2.7 years (95% confidence interval = [1.5 years, 3.8 years]) of cortical brain age at follow‐up. Additional regional analyses yielded bilateral effects on multiple frontal cortical regions. Our findings highlight the role of cardiac structure in brain aging. LVMI constitutes an easily measurable marker that might help to identify persons at risk for cognitive impairment and dementia.
The effect of relaxing music on driving anger and performance in a simulated car‐following task
Authors: Zhang Qian , Ge Yan , Qu Weina
Published: February 2024

Studies have focused on the negative effects of anger on driving performance, but insufficient research has addressed intervention methods to reduce these emotional effects. This research investigated how music mitigates the deterioration of driving performance associated with angry emotions in a simulated car‐following task. Forty‐three licensed drivers participated in this study, and they were randomly separated into two groups: an intervention group and a control group. First, all the participants completed a car‐following task involving neutral arousal. Then, both groups completed the car‐following task after the anger arousal task. The intervention group drove while listening to relaxing music, but the control group did not. Driving performance and electrocardiographic data were recorded. The results showed that participants who listened to relaxing music had significantly shorter braking reaction times and greater heart rate variability (HRV) than did those who did not listen to music. Relaxing music can reduce driving anger and improve driving behavior.
Inter‐regional patient mobility in decentralised Spain: Explaining regional budget imbalances
Authors: Cruz‐Martinez Gibran , Perna Roberta , Moreno Fuentes Francisco Javier
Published: February 2024

Inter‐regional patient mobility represents both a resource and a challenge for the organization and financing of health systems, particularly in decentralised countries. We use cross‐sectional time series regression analysis to test the determinants of imbalances in regional funds to finance inter‐regional patient mobility for the 17 Spanish regions for the period 2014–2020. The findings indicate that highly specialised health centres and bilateral agreements partly explain the budget imbalance from inter‐regional patient referrals, while local tourism partly explains the budget imbalance from non‐referred patient mobility. Developing effective national schemes to compensate net patient recipient regions would be fundamental to addressing territorial imbalances.
Evaluation of the efficacy of a sunscreen containing ultra‐long UVA1 and other UVR broad‐spectrum filters on skin barrier protection and melanin content reduction in Chinese adults: A single‐center study
Authors: Zhang Xianghua , Tao Han , Zhang Zhongxing , Wang Wenna , Steel Andrew , Fang Xiaofeng , He Xiaofeng
Published: February 2024

Background and Aims

The protection for ultra‐long UVA1 is lacked in the market, posing potential damage from ultra‐long UVA1 irradiation. The study aims to evaluate the efficacy of a sunscreen containing multiple components, especially Mexoryl® 400 for improving skin barrier function and reducing melanin content.

Methods

This single‐center study included adults with sensitive and normal skin in China in November 2022. Participants received the test sunscreen for 4 weeks. Melanin and hemoglobin content, sebum secretion skin hydration, and trans‐epidermal water loss were evaluated at T0d, T7d, and T28d. The self‐assessment was done at T15min, T7d, and T28d.

Results

Sixty participants were included, including 30 self‐claimed sensitive skin in the sunscreen group. The sunscreen demonstrated significant improvements in skin parameters. Skin redness reduced by 9.84% at T28d, sebum content in the forehead area decreased by 22.70% at T28d, and skin stratum corneum hydration increased by 38.44% at T28d, p < 0.001 respectively. Most notably, skin melanin content significantly reduced by 13.49% after 4 weeks' usage (p < 0.001). No adverse reactions were reported in either group.

Conclusions

The study sunscreen improved the skin condition by decreasing the melanin content, regulating skin barrier function, and achieving a balance of skin hydration and sebum secretion.
Advances in the use of organoids in endometrial diseases
Authors: Liu Yaofang , Sun Yue , Cheng Shaolong
Published: February 2024

The endometrium undergoes cyclical changes in response to hormones and there is a certain degree of heterogeneity among individuals. In vivo identification of the physiologic changes of the endometrium and the pathologic process of related diseases is challenging. There have been recent advances in the use of organoids that mimic the characteristics of the corresponding organs and the morphologic, functional, and personalized characteristics involved in different stages of diseases. In this paper, we discuss the process of creating endometrial organoids, cell sources, types of extracellular matrices, and their application in the study of physiologic endometrial states and various diseases.
Clinical characteristics and pregnancy outcome analysis of 20 cases of acute pancreatitis during pregnancy
Authors: Zhou Dong , Sun Guoqiang , Hu Jing , Gan Quan
Published: February 2024

Objective

This study investigated the clinical characteristics and pregnancy outcomes of acute pancreatitis during pregnancy (APIP).

Methods

A retrospective analysis was conducted on 20 cases of APIP admitted to Hubei Maternal and Child Health Hospital from January 2017 to September 2021. The etiology, clinical manifestations, and perinatal outcomes of APIP were analyzed using descriptive statistical analysis of the collected data.

Results

The incidence of APIP in our hospital was 20 (0.02%) cases, all of which occurred in the late stage of pregnancy. Hypertriglyceridemic acute pancreatitis (HTG‐AP) was the primary cause of APIP in 10 (50.0%) patients. A total of 11 (55.0%), seven (35.0%) and two (10.0%) patients had mild acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), respectively. Pregnant women with HTG‐AP had significantly elevated serum triglyceride levels, had higher prepregnancy body mass indices, were more prone to developing diabetes and were more likely to progress to SAP. With a multidisciplinary approach and individualized treatment plans, there were no maternal deaths, and fetal death only occurred in one (5.0%) case.

Conclusion

HTG‐AP is prone to advancing to more severe states, and it is becoming more common every year. Therefore, blood lipid management during pregnancy should be emphasized. Pregnant women with digestive symptoms or severe hyperlipidaemia should be screened for APIP in a timely manner and receive clinical intervention to improve maternal and fetal outcomes during the perinatal period.
Cesarean sections and sociodemographic disparities in Ecuador: A nationwide study from hospital registries between 2015 and 2022
Authors: Lapo‐Talledo German Josuet
Published: February 2024

Objective

This study aimed to analyze sociodemographic factors associated with cesarean sections (c‐sections) in Ecuador.

Methods

Data were extracted from the Ecuadorian National Institute of Statistics and Censuses (INEC). Multivariate binary and multinomial logistic regression analyses were performed to assess sociodemographic factors associated with c‐sections overall and with each type of c‐section (elective or emergency c‐section).

Results

This study included 1 118 842 in‐hospital deliveries during 2015–2022 in Ecuador, of which 41.3% were c‐sections. This exceeds the recommended levels of medical justified c‐sections. Those who were older than 20–29 years showed a higher probability for c‐sections overall. Regarding ethnicity, Montubios had 57% higher probability for c‐sectioned with an adjusted odds ratio (aOR) of 1.57 and a 95% confidence interval (CI) of 1.45–1.71; while indigenous, black, and white individuals exhibited 73%, 29%, and 21% lower probabilities, respectively. However, this varied according to specific type of c‐sections: black individuals had 11% higher probability of elective c‐section but 44% lower probability of emergency c‐section. Deliveries in private healthcare facilities exhibited significantly higher probabilities of c‐sections overall (aOR 15.38, 95% CI 15.20–15.56). Higher probability of emergency c‐section was also observed during 2020–2022.

Conclusion

Cesarean sections in Ecuador still exceed the recommended levels of medically justified c‐sections, highlighting the importance of adopting an approach to childbirth that reduces unnecessary interventions. These results suggest an important role of sociodemographic factors, which aligns with the reported need for multicomponent and locally tailored strategies for addressing c‐section overuse. The increase in c‐sections during the COVID‐19 pandemic (2020–2022) might suggest the influence of external health crises on maternal healthcare.
Establishing carrier transport channels based on TiS bonds and enhancing the photocatalytic performance of MXene quantum dots–ZnIn2S4 for ammonia synthesis
Authors: Cheng Xueying , Guan Renquan , Wu Zhengkai , Sun Yingnan , Che Weilong , Shang Qingkun
Published: February 2024

In the process of photocatalytic synthesis of ammonia, the kinetics of carrier separation and transport, adsorption of nitrogen, and activation of the NN triple bond are key factors that directly affect the efficiency of converting nitrogen to ammonia. Here, we report a new strategy for anchoring MXene quantum dots (MXene QDs) onto the surface of ZnIn2S4 by forming TiS bonds, which provide a channel for the rapid separation and transport of charge carriers and effectively extend the lifespan of photogenerated carriers. The unique charge distribution caused by the sulfurization of the MXene QDs further enhances the performance of the photocatalysts for the adsorption and activation of nitrogen. The photocatalytic ammonia synthesis efficiency of MXene QDs–ZnIn2S4 can reach up to 360.5 μmol g−1 h−1. Density functional theory calculations, various in situ techniques, and ultrafast spectroscopy are used to characterize the successful construction of TiS bonds and the dynamic nature of excited state charge carriers in MXene QDs–ZnIn2S4, as well as their impact on nitrogen adsorption activation and photocatalytic ammonia synthesis efficiency. This study provides a new example of how to improve nitrogen adsorption and activation in photocatalytic material systems and enhance charge carrier dynamics to achieve efficient photocatalytic nitrogen conversion.

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The complex relationship between late‐onset caloric restriction and synaptic plasticity in aged Wistar rats
Authors: Prvulovic Milica , Sokanovic Srdjan , Simeunovic Valentina , Vukojevic Andjela , Jovic Milena , Todorovic Smilja , Mladenovic Aleksandra
Published: February 2024

Age‐related reduction in spine density, synaptic marker expression, and synaptic efficiency are frequently reported. These changes provide the cellular and molecular basis for the cognitive decline characteristic for old age. Nevertheless, there are several approaches that have the potential to ameliorate these processes and improve cognition, caloric restriction being one of the most promising and widely studied. While lifelong caloric restriction is known for its numerous beneficial effects, including improved cognitive abilities and increased expression of proteins essential for synaptic structure and function, the effects of late‐onset and/or short‐term CR on synaptic plasticity have yet to be investigated. We have previously documented that the effects of CR are strongly dependent on whether CR is initiated in young or old subjects. With this in mind, we conducted a long‐term study in aging Wistar rats to examine changes in the expression of several key synaptic markers under the regimen of CR started at different time points in life. We found a significant increase in the expression of both presynaptic and postsynaptic markers. However, taking into account previously reported changes in the behavior detected in these animals, we consider that this increase cannot represent beneficial effect of CR.
Colonic Transit Time in Constipated Children: Does Pediatric Slow‐Transit Constipation Exist?
Authors: Benninga M. A. , Büller H. A. , Tytgat G. N. J. , Akkermans L. M. A. , Bossuyt P. M. , Taminiau J. A. J. M.
Published: February 2024

In adults, slow‐transit constipation is a wellestablished form of constipation with abdominal pain and an empty rectum on examination. Marker studies in these patients, mainly women, show a markedly slowed transit time in all colonic segments. No studies in constipated children are available that assess the existence of slowtransit constipation. In a prospective study, a total of 94 referred constipated pediatric patients, 63 boys and 31 girls (median age, 8.0 years), underwent colonic‐transittime measurements using radioopaque markers to evaluate the pattern of transit. In addition, orocecal‐transittime measurements using the hydrogen breath (lactulose) test, anorectal manometry, and behavior studies using the Child Behavior Checklist were performed in all children. Based on the upper limit (mean + 2 SD) of total colonic transit time (CTT) in constipated children, we arbitrarily separated patients into two groups. Children with CTTs >100 h were said to have pediatric slow‐transit constipation (PSTC), while patients with CTTs <100 h were said to have normal‐ or delayed‐transit constipation (NDTC). In 94 constipated children, PSTC was found in 24 children; in 70 children, total CTT was <100 h (NDTC). Total and segmental CTTs were significantly prolonged in PSTC (median, 189 h; range, 104.4‐384) versus NDTC (median, 46.8 h; range, 3.6‐99.4) hours. No significant differences were found in orocecal transit time. Significant clinical differences in children with PSTC versus those with NDTC existed regarding nighttime soiling (71 vs. 11%); daytime soiling episodes (14 vs. 7 each week, median), and nighttime soiling episodes (5 vs. 0 each week, median); absent urge to defecate (33 vs. 14%); and palpable abdominal (71 vs. 39%) and/or rectal (71 vs. 13%) masses. All manometric parameters were comparable in the two groups, except for a significantly lower maximal squeeze pressure with PSTC. Using the Child Behavior Checklist, both groups differed significantly from controls (26 and 43%, respectively), with no significant differences in behavior problems found between the NDTC and the PSTC groups. In conclusion, based on objective marker studies, our findings suggest the existence of pediatric slow‐transit constipation. This entity can be recognized by clinical features, most importantly nighttime soiling and a palpable rectal mass. The probability of PSTC with both of these symptoms was 0.82; in the absence of these two symptoms, it was 0.07. It is of interest that CTTs in PSTC are comparable with CTTs in adults with slow‐transit constipation, although the clinical presentation is clearly different. Further studies are needed to investigate whether the prolonged CTT characterizes a distinct form of constipation in children or is an epiphenomenon of the underlying constipation itself. The mechanisms responsible for the slow transit in these children and the appropriate therapeutic approach need to be studied.
Improving the Palatability of Oral Rehydration Solutions Has Implications for Salt and Water Transport: A Study in Animal Models
Authors: Dias J. A. , Thillainayagam A. V. , Hoekstra H. , Walker‐Smith J. A. , Farthing M. J. G.
Published: February 2024

It is believed that improving the taste of oral rehydration solutions (ORSs) might lead to greater patient acceptability. A pilot trial showed that replacing glucose with sucrose and increasing the citrate concentration at the expense of chloride improves palatability. However, the transport implications of such modifications are not known. Three hypotonic experimental ORSs (Suc/cit‐ORS, 211 mosmol/kg; Suc/Cl‐ORS, 224 mosmol/kg; and Glu‐ORS, 224 mosmol/kg) were compared with a standard European ORS (Euro‐ORS, 265 mosmol/kg) by in vivo perfusion of entire rat small intestine in normal adult rats and rotavirus‐infected neonates. All ORSs were of identical sodium, potassium, chloride, and citrate content except that in the Suc/cit‐ORS, chloride was removed in favor of increased citrate, and the chloride concentration in Euro‐ORS was higher than in the others. Suc/cit‐ORS and Suc/Cl‐ORS had glucose partially replaced by sucrose while Glu‐ORS and Euro‐ORS contained only glucose. In normal small intestine, water absorption was greater from Glu‐ORS than Suc/cit‐ORS or Euro‐ORS, although water absorption was similar from Suc/cit‐ORS and Suc/Cl‐ORS. In the rotavirus model, Glu‐ORS produced more water absorption than Euro‐ORS or either sucrose ORS. In both models, Suc/cit‐ORS caused sodium and chloride secretion. Glucose absorption was similar from all ORSs. These findings indicate that attempts to improve ORS palatability by adding sucrose or increasing citrate at the expense of chloride would incur a significant penalty in terms of salt and water absorption.
The Role of Magnesium in the Pathogenesis of Bone Disease in Childhood Cholestatic Liver Disease: A Preliminary Report
Authors: Heubi James E. , Higgins James V. , Argao Eric A. , Sierra Rosa I. , Specker Bonny L.
Published: February 2024

Background:

Magnesium deficiency may contribute to the metabolic bone disease that complicates chronic cholestatic liver disease. We hypothesized that magnesium deficiency alters vitamin D metabolism by decreasing parathyroid hormone (PTH) response, resulting in decreased serum osteocalcin and decreased bone accretion.

Methods:

Nine subjects, age 3‐22 years, with cholestatic liver disease were evaluated with the magnesium retention test. The response of PTH, 1,25(OH)2 vitamin D, and osteocalcin to provocative stimuli and dual x‐ray absorptiometry measurement of bone mineral density (BMD) of the lumbar spine were assessed. Thereafter, subjects were treated with oral magnesium supplements.

Results:

All nine subjects were magnesium depleted. Repletion with magnesium was successful in seven subjects, and required 4 to 31 (median 14) months with doses of 6 to 34 (median 11) mg/kg/day. Baseline serum PTH was significantly reduced in the cholestatic subjects compared to 15 age‐matched controls. Comparison of baseline to repleted provocative testing was performed in six Mg‐repleted subjects. Osteocalcin response increased significantly (p = 0.048) with repletion, while PTH response increased (p = 0.061). Lumbar spine BMD increased modestly with repletion (p = 0.093).

Conclusions:

This preliminary report suggests that magnesium depletion is extremely common in children with chronic cholestasis. We speculate that magnesium supplementation may be warranted to forestall the progression of metabolic bone disease in chronic cholestasis.
Essential Fatty Acids and Their Trans Geometrical Isomers in Powdered and Liquid Infant Formulas Sold in Canada
Authors: Ratnayake W. M. N. , Chardigny J. M. , Wolff R. L. , Bayard C. C. , Sébédio J. L. , Martine L.
Published: February 2024

Background

Animal and human studies have suggested that trans fatty acids might alter some physiological functions and adversely affect the growth and essential fatty acid balance of infants. In this context it is important to know the fatty acid composition, including the levels of trans isomers of oleic, linoleic and α‐linolenic acids in infant formulas.

Methods

Ten liquid and fourteen powdered formulas for term infants were purchased from retail stores in Canada. The fatty acid composition of each formula was determined by capillary gas‐liquid chromatography.

Results

All the formulas met the mimimum content of 500 mg of linoleic acid/100 kcal formula (equivalent to 4.5% of energy) specified under current Canadian regulations. The formulas all met the minimum energy levels of 3% as linoleic acid and 0.7% as α‐linolenic acid recommended recently by an ad hoc committee of Health Canada. However, in nine formulas, the proportion of linoleic acid was more than 20% of total fatty acids, and consequently, in five of them, the ratio of linoleic acid to α‐linolenic acid exceeded the maximum ratio of 16:1 recommended by the ad hoc committee. Trans fatty acids were present in all the samples, and generally the liquid formulas displayed a higher total trans content (mean 1.9%, range 0.9‐3.1%) than powdered formulas (mean 1.4%, range 0.6‐2.5%). The amounts of trans isomers of linoleic and α‐linolenic acids and the degree of isomerization of these fatty acids were also higher in liquid formulas than in powdered formulas.

Conclusions

A few of the Canadian infant formulas would provide one‐third of α‐linolenic acid as trans geometric isomers.
Nitric Oxide and the Intestinal Epithelial Barrier: Does it Protect or Damage the Gut?
Authors: Blikslager Anthony T. , Roberts Malcolm C. , Bijleveld Charles , Buller Hans , Taminiau Jan , Thomas Adrian , Lichtman Steven N. , Shneider Benjamin L. , Bishop Warren P. , Haber Barbara Anne
Published: February 2024

Nitric Oxide Dilates Tight Junctions and Depletes ATP in Cultured Caco‐2BBe Intestinal Epithelial Monolayers. Salzman AL, Menconi MJ, Unno N, Ezzell RM, Casey DM, Gonzalez PK, Fink MP.
Reverse Transcription‐Polymerase Chain Reaction in the Diagnosis of Helicobacter pylori Infection in Finnish Children
Authors: Oksanen Katri , Kainulainen Heikki , Ruuska Tarja , Mäki Markku , Ashorn Merja
Published: February 2024

Background:

The purpose of this study was to design a simplified polymerase chain reaction (PCR) technique for the detection of Helicobacter pylori and to compare it with conventional diagnostic methods‐culture and histology of gastric biopsy specimens. In addition, the capability of this technique to detect H. pylori in the gastric mucosal biopsies of originally H. pylori‐negative children with gastritis or recurrent abdominal pain was investigated.

Methods:

Reverse transcriptase polymerase chain reaction (RT‐PCR) using polymerase from Thermus thermophilus was applied to detect H. pylori 16S rRNA. Twenty‐five children H. pylori‐positive by culture and/or histology were used as positive control subjects. Sixteen healthy H. pylori‐negative children served as negative control subjects. Biopsy specimens from gastric antrum and corpus from 81 children were examined by RT‐PCR. Altogether, 30 had histologic gastritis and 51 had nonspecific abdominal pain only, with no disease in histologic specimens. Histology and culture of H. pylori were negative in both patient groups.

Results:

Reverse transcription‐polymerase chain reaction detected 24 of 25 tissue‐positive and 0 of 16 tissue‐negative cases, indicating 96% sensitivity and 100% specificity for the test. None of the culturally and histologically H. pylori‐negative samples showed H. pylori colonization when analyzed by RT‐PCR.

Conclusions:

RT‐PCR using Thermus thermophilus polymerase is a fast and simple means of detecting H. pylori in gastric biopsy specimens. It is at least as specific and sensitive as conventional methods. In pediatric patients it may be necessary to take more than two biopsy specimens to increase sensitivity in cases of local or patchy colonization.
The Effects of Acetylsalicylic Acid, Interferon‐α, and Vitamin E on Prevention of Parenteral Nutrition‐Associated Cholestasis: An Experimental Study
Authors: Demircan Mehmet , Uguralp Sema , Mutus Murat , Gurer E. Inanc , Atik Esin , Turhan Fahri , Gursoy M. Harun
Published: February 2024

Background:

Cholestasis is one of the major complications of parenteral nutrition. The purpose of this experimental study was to detect the effects of acetylsalicylic acid (ASA), vitamin E (Vit E), and interferon‐α (IFN‐α) on prevention of parenteral nutrition‐associated cholestasis.

Methods:

Ten experimental groups, each consisting of 10 4‐week‐old Wistar albino rats, were formed: control 10‐ and 20‐day groups (C10 and C20), parenteral nutrition‐only 10‐ and 20‐day groups (T10 and T20), ASA‐supplemented parenteral nutrition 10‐ and 20‐day groups (TA10 and TA20), Vit E‐supplemented parenteral nutrition 10‐ and 20‐day groups (TE10 and TE20), and IFN‐α‐supplemented 10‐ and 20‐day groups (TF10 and TF20). Acetylsalicylic acid, Vit E, and IFN‐α were administered in the parenteral nutrition solution through an intraperitoneal route. At the end of the study, serum total bile acids, serum aspartate and alanine aminostransferases, and alkaline phosphatase were measured biochemically. In addition, the histopathologic findings of cholestasis were evaluated by using a morphologic portal inflammation index.

Results:

Although the difference in the serum levels of transferases and alkaline phosphatase was not significant among all groups (p > 0.05), it was significant in total bile acid levels (p < 0.05). There was also a significant correlation between the histopathologic changes of the liver and serum total bile acid concentrations (p < 0.05). Portal inflammation in varying degrees was seen in all experimental groups, but not in the control groups. Serum total bile acid concentrations in parenteral nutrition groups receiving ASA were significantly lower than those in the parenteral nutrition‐only group (p < 0.01). Although Vit E‐supplemented parenteral nutrition was effective in preventing the development of cholestasis in the 10‐day group (p < 0.05), it was not effective in the 20‐day group when compared with incidence of cholestasis in the parenteral nutrition‐only group (p > 0.05). Conversely, IFN‐α‐supplemented parenteral nutrition had no effect on cholestasis in the 10‐day group (p > 0.05) but lowered cholestasis in the 20‐day group when compared with incidence the parenteral nutrition‐only group (p < 0.05).

Conclusion:

Our results indicate that acetylsalicylic acid may be beneficial in preventing, and α‐interferon in treating, parenteral nutrition‐associated cholestasis.
Severe and Protracted Diarrhea: Results of the 3‐Year SIGEP Multicenter Survey
Authors: Catassi Carlo , Fabiani Elisabetta , Spagnuolo Maria Immacolata , Barera Graziano , Guarino Alfredo ,   the Working Group of the Italian Society of Pediatric Gastroenterology and Hepatology (SIGEP)
Published: February 2024

Background:

The spectrum of severe and protracted diarrhea (SPD), previously defined as intractable diarrhea, has changed during the past several decades. Despite recent advances in determining the cause of SPD and in treatment, this syndrome still represents a challenge and is becoming a major problem affecting health care resources. This study was conducted to characterize the epidemiology, spectrum of causes, and the outcome of SPD in Italy in recent years.

Methods:

All the SPD cases seen at the major centers of pediatric gastroenterology in Italy during a 3‐year period (1993‐1996) were recruited in this multicenter, prospective survey.

Results:

Thirty‐two children (26 boys and 6 girls; median age at the onset of SPD, 40 days) were enrolled in this study by 9 of 26 participating centers. Twelve were newly diagnosed cases, with an estimated SPD incidence rate in Italy of 0.64 to 0.92 × 10‐5 infants per year. The most common causes were autoimmune enteropathy (n = 8) and ultrastructural abnormalities of the enterocyte (n = 7), whereas food intolerance and postenteritis syndrome were less frequent (3 and 2 cases, respectively). Two children with autoimmune enteropathy fulfilled the criteria for the X‐linked variant of this condition. At the end of the study period, 9 of 31 patients had recovered, 15 still had diarrhea, and 7 had died.

Conclusions:

Severe and protracted diarrhea is a rare but challenging problem in Italy. Because parenteral nutrition or intestinal transplantation are the only options in a subset of cases (e.g., ultrastructural abnormalities of the enterocyte), infants with SPD should be referred to specialized centers where advanced diagnostic and therapeutic facilities are available.
Measurement of Low Dietary Fiber Intake As a Risk Factor for Chronic Constipation in Children
Authors: Morais Mauro B. , Vítolo Márcia R. , Aguirre Andrea N. C. , Fagundes‐Neto Ulysses
Published: February 2024

Background:

Scarce information exists regarding dietary fiber intake in children with chronic constipation. The objective of this case‐control study was to evaluate the intake of fiber as a risk factor for chronic constipation.

Methods:

Fifty‐two children with a mean age of 6.8 ± 3.2 years who had chronic constipation were age and gender matched with 52 children with normal intestinal habits. The fiber content of the diet was evaluated with a 24‐hour dietary recall. Two tables of fiber composition in foods were used: a Brazilian table, and a table based on the method of the Association of Official Agricultural Chemists (AOAC).

Results:

According to the Brazilian table, the median intake of fiber (in grams per day) by the constipated and the control groups was 13.8 and 17.3, respectively, for total fiber (p = 0.020), 6.8 and 9.7 for insoluble fiber (p = 0.004), and 6.5 and 7.6 for soluble fiber (p = 0.104). According to the AOAC table, the constipation group (9.7 g/day) also had lower (p = 0.0022) intake of total fiber than the control group (12.6 g/day). The coefficient of correlation between the two tables on fiber content of food was +0.82 (p < 0.001) in the constipation group and +0.86 (p < 0.001) in the control group. The intake of fiber was less than the minimum recommendation (age + 5 g) and statistically associated (p = 0.001) with the constipation group (75.0%) in comparison with the controls (42.5%). The odds ratio was 4.1 (95% confidence limits, 1.64‐10.32).

Conclusion:

Intake of fiber below the minimum recommendation is a risk factor for chronic constipation in children.
The Use of Focus Groups to Define Patient Needs
Authors: Barbour Rosaline S.
Published: February 2024

Focus groups are enjoying unprecedented popularity. In this article, the advantages and disadvantages of the method are outlined with cautions against the uncritical adoption of focus groups designed according to the marketing research tradition. It is argued that focus groups require detailed planning, and some advice regarding the running of groups, and analysis of data is provided. Special attention is directed to the practical and ethical issues in using focus groups to define patient needs in the area of childhood inflammatory bowel disease. Finally, some suggestions for maximising the full potential of focus groups are presented. Focus groups, if used appropriately and judiciously, are an inherently flexible method. Ultimately, their use is constrained only by the research question and the imagination of the researcher.
Nonalcoholic Steatohepatitis in Children
Authors: Rashid Mohsin , Roberts Eve A.
Published: February 2024

Background:

Nonalcoholic steatohepatitis occurs commonly in adults with obesity or diabetes mellitus. There are only a few reports of this condition in children.

Methods:

Prospective consecutive clinical series.

Results:

Between December 1985 and April 1995, 36 children (21 boys, 15 girls) were diagnosed with nonalcoholic steatohepatitis at the Hospital for Sick Children, Toronto. The median age at diagnosis was 12 years (range, 4–16 years). Most patients were referred because of elevated serum aminotransferases or abnormal hepatic sonogram. Thirty patients (83%) were obese. Two patients had diabetes mellitus at diagnosis, and it developed later in two. Fifteen patients had palpable hepatomegaly, and one of these had splenomegaly. None had physical signs of chronic liver disease. Thirteen of 36 patients had acanthosis nigricans. Serum aminotransferases were elevated in all but one patient. Tests for Wilson disease and chronic hepatitis B and C were negative. Serum lipid profiles were abnormal in 18 patients: 7 had hypercholesterolemia, and 11 had hypertriglyceridemia. Twenty‐four of 31 examined had abnormal liver sonograms suggestive of fatty infiltration. Twenty‐four patients underwent percutaneous liver biopsy: all showed large‐droplet fat. Inflammation was present in 88% and fibrosis‐cirrhosis in 75%. One 10‐year‐old patient had established cirrhosis at diagnosis.

Conclusions:

Nonalcoholic steatohepatitis occurs in children, is clinically diverse, and may not be benign.
Analysis of Intestinal Flora Development in Breast‐Fed and Formula‐Fed Infants by Using Molecular Identification and Detection Methods
Authors: Harmsen Hermie J. M. , Wildeboer–Veloo Alida C. M. , Raangs Gerwin C. , Wagendorp Arjen A. , Klijn Nicolette , Bindels Jacques G. , Welling Gjalt W.
Published: February 2024

Background:

An obvious difference between breast‐fed and formula‐fed newborn infants is the development of the intestinal flora, considered to be of importance for protection against harmful micro‐organisms and for the maturation of the intestinal immune system. In this study, novel molecular identification methods were used to verify the data obtained by traditional culture methods and to validate the culture independent fluorescent in situ hybridization (FISH) technique.

Methods:

From each of six breast‐fed and six formula‐fed newborn infants, six fecal samples were obtained during the first 20 days of life. The microbial compositions of the samples were analyzed by culturing on specific media and by FISH, by using specific 16S rRNA‐targeted oligonucleotide probes. The colonies growing on the media were identified by random amplified polymorphic DNA pattern analysis and by polymerase chain reaction amplification and subsequent analysis of the 16S rRNA gene.

Results:

Molecular identification of the colonies showed that the selective media are insufficiently selective and unsuitable for quantitative analyses. Qualitative information from the culturing results combined with the data obtained by the FISH technique revealed initial colonization in all infants of a complex (adult‐like) flora. After this initial colonization, a selection of bacterial strains began in all infants, in which Bifidobacterium strains played an important role. In all breast‐fed infants, bifidobacteria become dominant, whereas in most formula‐fed infants similar amounts of Bacteroides and bifidobacteria (∼40%) were found. The minor components of the fecal samples from breast‐fed infants were mainly lactobacilli and streptococci; samples from formula‐fed infants often contained staphylococci, Escherichia coli, and clostridia.

Conclusions:

This study confirms the differences in development of intestinal flora between breast‐fed and formula‐fed infants. The results obtained from the FISH technique were consistent. Although the repertoire of probes for this study was not yet complete, the FISH technique will probably become the method of reference for future studies designed to develop breast‐fed–like intestinal flora in formula‐fed infants.
Influence of Age on 13C‐Urea Breath Test Results in Children
Authors: Kindermann Angelika , Demmelmair Hans , Koletzko Berthold , Krauss–Etschmann Susanne , Wiebecke Baldur , Koletzko Sibylle
Published: February 2024

Background:

The 13C‐urea breath test for diagnosis of Helicobacter pylori infection has not been validated in infants and young children. The influence of age on the test results was studied by conventional validation against invasive methods and by mathematical estimation in a large pediatric population.

Methods:

The breath test was performed in 1499 children aged 2 months to 18 years. After a fasting period of 4 hours or more, 75 mg 13C‐urea was ingested with cold apple juice, breath samples were taken at baseline and at 15 and 30 minutes. The distribution of the natural logarithms of the Δ‐over baseline (DOB) values were calculated, and the optimal cutoff values between positive and negative test results and gray zones with a risk of misclassification more than 10% were determined for both time points. In a subgroup of 149 children results of the breath test were compared with concordant results of histology and rapid urease test; 53 of them were less than 6 years of age.

Results:

Logarithmic results of 1499 breath tests revealed two normally distributed subgroups with minimal overlap. The calculated optimal cutoff values were 4.7‰ at 15 minutes and 5.0‰ at 30 minutes. At 30 minutes, only 2.6% of all results were in the calculated gray zone (2.6–6.5‰). Age was negatively correlated to DOB values of both negative (r = −0.223) and positive results (r = −0.291;P < 0.001). Breath test–negative and –positive children 6 or less years of age had significantly higher mean DOB values (P < 0.02) and a larger proportion of results within the gray zone than older children. Compared with biopsy‐based results, the least discrepancies occurred at a cutoff of 5.0‰: 0 of 61 infected (sensitivity 100%) and 6 of 88 noninfected children. Because five of the false‐positive results were obtained in children less than 6 years of age, specificity and positive predictive values were lower in this age group than in older patients (88.1% vs. 97.8% and 68.8% vs. 98.0%, respectively).

Conclusions:

Under the applied conditions, the 13C‐urea breath test shows an excellent separation between positive and negative results. Because of some overlap and a strong age effect, definition of a gray zone appears more meaningful than a threshold value. Because infants and young children have a high risk for false‐positive breath test results, the values for cutoff and gray zones may have to be adapted. Further validation studies against invasive methods are warranted in this age group.
Antibody Reactivity Against Human and Guinea Pig Tissue Transglutaminase in Children with Celiac Disease
Authors: Hansson Tony , Dahlbom Ingrid , Hall Jeanette , Holtz Anette , Elfman Lena , Dannaeus Anders , Klareskog Lars
Published: February 2024

Background:

Highly discriminatory markers for celiac disease are needed to identify children with early mucosal lesions. The purposes of this study were to evaluate the clinical potential of circulating anti‐tissue transglutaminase (tTG) immunoglobulin (Ig)A antibodies in the diagnosis of childhood celiac disease and to investigate the extent of autoreactivity of these antibodies.

Methods:

Included in this retrospective study were samples from 22 children with biopsy‐verified celiac disease, 23 control subjects with disease, and 22 healthy control subjects without any known gastrointestinal or inflammatory disorders. An enzyme‐linked immunosorbent assay (ELISA) was used to measure the serum levels of IgA antibodies specific for human and guinea pig tTGs. All samples were also analyzed for antibodies to gliadin and endomysium (EMA).

Results:

The concentrations of IgA specific for human and guinea pig tTGs correlated with the small intestinal villous structure and the serum levels of IgA EMA. The tTG ELISAs exhibited a high specificity and sensitivity for detection of untreated celiac disease. The human erythrocyte IgA tTG ELISA had the highest sensitivity (100%) and a specificity of 98%. The IgA EMA method had a sensitivity of 95% and the highest specificity (100%) of all tests.

Conclusions:

Our results provide additional support to the concept that anti‐tTG IgA antibodies can be used as a highly discriminatory serologic marker for celiac disease and that measurements of these autoreactive antibodies may in the future be used as an alternative to the EMA test.
Management of Acute Gastroenteritis in Europe and the Impact of the New Recommendations: A Multicenter Study
Authors: Szajewska Hanna , Hoekstra J. Hans , Sandhu Bhupinder ,   The Working Group on Acute Diarrhoea of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition
Published: February 2024

Background

The European Society for Paediatric Gasteroenterology, Hepatology and Nutrition (ESPGHAN) issued two sets of recommendations for the treatment of infants with acute gastroenteritis (1992, 1997). The purpose of this multicentre study performed in 29 European countries was to determine how closely current treatment compares with the ESPGHAN recommendations.

Methods

The outline of the study was based on a questionnaire that addressed the management of a 6‐month‐old infant with acute gastroenteritis complicated by mild to moderate dehydration. National coordinators circulated the questionnaire to randomly selected primary care physicians and to hospital‐based paediatricians.

Results

A total of 2997 questionnaires were returned, of which 1768 were from Western Europe (WE) and 1229 from Central and Eastern Europe (CEE). Eighty‐four percent of responding physicians said they would follow the ESPGHAN recommendation to use oral rehydration solution (ORS) for rehydration, with 66% using an ORS containing 60 mmol/l sodium ORS. Only 16% (WE 15%, CEE 19%) would follow the guidelines and use rapid oral rehydration over 3 to 4 hours. Forty‐five percent would rehydrate infants in a 3‐to 6‐hour period (WE 35%, CEE 60%), and 17% (WE 23%, CEE 9%) would extend the rehydration period to 12 to 24 hours. ESPGHAN recommendation of rapid reintroduction of normal feeding after 3 to 4 hours of oral rehydration would be followed by only 21% of responding physicians, and only 43% (WE 46%, CEE 38%) would start feeding with full‐strength formula. However, the guideline about continuation of breast‐feeding is widely followed (total 77%; WE 78%, CEE 75%). Thirty‐six percent (WE 45%, CEE 23%) use a lactose‐containing formula after successful oral rehydration. Contrary to the ESPGHAN guideline 35% (WE 30%, CEE 42%) would use a lactose‐free formula and 19% (WE 12%, CEE 28%) a lactose and cow's milk protein–free formula. Only 37% (WE 30%, CEE 46%) of responding physicians would follow the recommendation to use ORS to replace ongoing losses from watery diarrhoea.

Conclusions

The results of the survey suggest that with the exception of recommending ORS for rehydration and continuation of breast‐feeding during diarrhoea, a minority of responding European physicians follow the ESPGHAN guidelines for optimal management of children with acute gastroenteritis.
Early Development of Human Gastric H,K‐Adenosine Triphosphatase
Authors: Grahnquist Lena , Ruuska Tarja , Finkel Yigael
Published: February 2024

Background

Little is known about the early development of the gastric acid secretion in human neonates. The purpose of this study was to examine the early development of gastric H,K‐adenosine triphosphatase (ATPase) by analyzing human gastric biopsy specimens.

Methods

Eighty‐eight neonates from week 25 to week 42 of gestation who were treated in a neonatal intensive care unit underwent gastroscopy with biopsy specimens obtained from the corpus. The expression of gastric H,K‐ATPase protein in the gastric biopsy specimens was assessed by Western blot analysis, using an antibody directed against the gastric H,K‐ATPase. The amount of H,K‐ATPase expressed was compared with age, gender, clinical factors, diseases, and the macroscopic and histologic findings at endoscopy.

Results

The expression of human gastric H,K‐ATPase increased significantly with gestational age. There was a significant increase in the expression of gastric H,K‐ATPase during the first 82 days after birth. Boys had a significantly higher expression of gastric H,K‐ATPase than girls did, when it was adjusted for gestational and postnatal age. Neither the clinical features nor treatments showed significant correlations with the expression of human gastric H,K‐ATPase when controlling for gestational and postnatal age.

Conclusions

This study shows that human gastric H,K‐ATPase is expressed from week 25 of gestation, which agrees with earlier findings of gastric pH in preterm infants. The amount of enzyme expressed increases with gestational and postnatal age. The authors speculate that the susceptibility to gastric lesions seen in neonates is not related to the amount of H,K‐ATPase. However, studies elucidating the ontogeny of gastric mucosal defense mechanisms are warranted.
Effect of Intravenous Lipid Emulsions on Hepatic Cholesterol Metabolism
Authors: Whitfield Phillip D. , Clayton Peter T. , Muller David P.R.
Published: February 2024

Background

Total parenteral nutrition offers the chance of survival to children who have had extensive gut resections or gut failure. However, in infants it is often associated with serious complications including cholestatic liver disease. The causes of these complications remain unclear, although it has been suggested that the lipid emulsions used in total parenteral nutrition may be responsible.

Methods

An in vitro system was developed to study the effect of lipid emulsions on hepatic cholesterol metabolism using cultured hepatocytes.

Results

Incubations of Hep G2 cells with medium containing Intralipid (Pharmacia and Upjohn, Milton Keynes, UK) demonstrated that the fat emulsion mediated a powerful dose‐dependent but reversible inhibition of cholesterol uptake. In addition Intralipid was shown to stimulate the efflux of cholesterol from Hep G2 cells. The component or components of the Intralipid responsible for these effects and the mechanism by which they act remain to be established.

Conclusions

Intravenous lipid emulsions may interfere with hepatic cholesterol metabolism in vivo. This may have implications for the development of total parenteral nutrition–associated cholestasis in neonates.