bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and Safety Measurements of Proton Pump Inhibitors in Infants and Children
Authors: James Laura P.
Published: January 2024

The design of studies to evaluate the efficacy of acid‐lowering drugs in children differs significantly from study designs in adult populations. Efficacy measurements may be less extensive than those used in adult studies because of limitations that exist secondary to concerns for patient safety, parental and institutional review board acceptance of efficacy end points, and existing standards of care within the pediatric gastroenterology community. Study designs involving patients who would routinely receive acid‐lowering therapy have been successfully used to characterize the pharmacokinetics and pharmacodynamics of acid‐lowering therapies (H2 receptor antagonists) and have led to pediatric labeling for these drugs. This approach may likewise be used in the study of newer acid‐lowering agents, such as proton pump inhibitors.
Proton Pump Inhibitors in Pediatrics: Relevant Pharmacokinetics and Pharmacodynamics
Authors: Kearns Gregory L. , Winter Harland S.
Published: January 2024

A marked discordance between the disposition of proton pump inhibitors (PPIs) in plasma and the kinetics of effect suggests the need for new approaches to characterize the clinical pharmacology of PPIs in infants and children. An assessment of pharmacokinetics and pharmacodynamics must take into account the genetic polymorphism of CYP2C19 and the impact of ontogeny on the activity of this and other enzymes (e.g., CYP3A4) which affect the biotransformation of the PPIs and, thus, their plasma clearance. In addition, the potential effects of extemporaneous formulations of the drugs on their rate and extent of absorption must be considered. Because of the apparent safety of PPIs and a well‐demonstrated dose–response–effect relationship in adults, pediatric pharmacokinetic data and an exposure correlate, such as the dose–area‐under‐the‐plasma‐concentration‐versus‐time‐curve relationship, can be used as a bridge to determine pediatric dosing.
Autonomic Neuropathy and Gastrointestinal Motility Disorders in Children and Adolescents With Type 1 Diabetes Mellitus
Authors: Vazeou A. , Papadopoulou A. , Papadimitriou A. , Kitsou E. , Stathatos M. , Bartsocas C. S.
Published: January 2024

Introduction

There is little information on the gastrointestinal motility abnormalities and autonomic neuropathy of children with gastrointestinal symptoms and type 1 diabetes mellitus (T1DM).

Methods

The authors studied 33 consecutive patients (mean age, 15.3 years; 13 males) with T1DM (median duration, 7.7 years) attending the outpatient clinic because of chronic dyspepsia (CD; n = 14), or chronic constipation (CC; n = 19), and 48 consecutive non‐T1DM patients (mean age, 13.7 years; 18 males), who presented with similar symptoms (18 with CD; 30 with CC). Fasting serum motilin concentrations and cardiovascular autonomic function tests (CAFT) were assessed and compared with those of age‐ and gender‐matched healthy control subjects. Gastric emptying half time (GE t1/2) of a solid meal and mouth‐to‐anus transit time (MATT) were measured in patients with CD and CC, respectively.

Results

CAFT was comparable between patients with T1DM and healthy control subjects. GE t1/2 and MATT were not different between T1DM patients and non‐T1DM patients with CD and CC, respectively. However, a marginally significant positive correlation was found in the patients with T1DM between GE t1/2 and blood glucose concentrations (R = 0.54; P = 0.08). In addition, serum motilin concentrations were significantly lower in patients with T1DM compared with healthy control subjects (P < 0.0005), and in patients with T1DM and higher serum glucose concentrations compared with those with lower serum glucose concentrations (P = 0.03).

Conclusion

Autonomic neuropathy is not an etiological factor of gastrointestinal symptoms in children and adolescents with diabetes. Mild or moderate hyperglycemia does not affect gastrointestinal motility.
Supplementary Feeding of Underweight, Stunted Malawian Children With a Ready‐To‐Use Food
Authors: Maleta Kenneth , Kuittinen Juha , Duggan Maureen B. , Briend André , Manary Mark , Wales Jerry , Kulmala Teija , Ashorn Per
Published: January 2024

Objective

Maize and soy flour mixes are often used in the treatment of moderate malnutrition in Malawi. Their efficacy has not been formally evaluated. A recently developed ready‐to‐use food (RTUF) effectively promotes growth among severely malnourished children. The authors compared the effect of maize and soy flour with that of RTUF in the home treatment of moderately malnourished children.

Methods

Sixty‐one underweight, stunted children 42 to 60 months of age were recruited in rural Malawi, in southeastern Africa. They received either RTUF or maize and soy flour for 12 weeks. Both supplements provided 2 MJ (500Kcal) of energy daily but had different energy and nutrient densities. Outcome variables were weight and height gain and dietary intake.

Results

Before intervention, the mean dietary intake and weight and height gain were similar in the two groups. During the supplementation phase, the consumption of staple food fell among children receiving maize and soy flour but not among those receiving RTUF. There was thus higher intake of energy, fat, iron, and zinc in the RTUF group. Both supplements resulted in modest weight gain, but the effect lasted longer after RTUF supplementation. Height gain was not affected in either group. Periodic 24‐hour dietary recalls suggested that the children received only 30% and 43%, respectively, of the supplementary RTUF and maize and soy flour provided.

Conclusions

RTUF is an acceptable alternative to maize and soy flour for dietary supplementation of moderately malnourished children. Approaches aimed at increasing the consumption of supplementary food by the selected recipients are needed.
Recurrent Abdominal Pain: Symptom Subtypes Based on the Rome II Criteria for Pediatric Functional Gastrointestinal Disorders
Authors: Walker Lynn S. , Lipani Tricia A. , Greene John W. , Caines Karen , Stutts John , Polk D. Brent , Caplan Arlene , Rasquin‐Weber Andree
Published: January 2024

Objectives

Recurrent abdominal pain (RAP) is a common childhood complaint rarely associated with organic disease. Recently, the Pediatric Rome Criteria were developed to standardize the classification of pediatric functional gastrointestinal disorders (FGIDs) using a symptom‐based approach. The authors tested the hypothesis that most patients with childhood RAP could be classified into one or more of the symptom subtypes defined by the Pediatric Rome Criteria.

Methods

Using a prospective longitudinal design, new patients with RAP (n = 114) were studied at a tertiary care children's medical center. Before the medical evaluation, parents completed a questionnaire about their child, assessing symptoms defined by the Pediatric Rome Criteria.

Results

Of the 107 children for whom medical evaluation revealed no organic etiology for pain, 73% had symptom profiles consistent with the Pediatric Rome Criteria for one of the FGIDs associated with abdominal pain (irritable bowel syndrome, 44.9%; functional dyspepsia,15.9%; functional abdominal pain, 7.5%; abdominal migraine, 4.7%)

Conclusions

This study provides the first systematic empirical evidence that RAP, originally defined by Apley, includes children whose symptoms are consistent with the symptom criteria for several FGIDs defined by the Rome criteria. The pediatric Rome criteria may be useful in clinical research to (1) describe the symptom characteristics of research participants who meet Apley's broad criteria for RAP, and (2) select patients with particular symptom profiles for investigation of potential biologic and psychosocial mechanisms associated with pediatric FGIDs.
Prolonged Monitoring of Esophageal Motor Function in Healthy Children
Authors: Chitkara Denesh K. , Fortunato Christine , Nurko Samuel
Published: January 2024

Objective

To describe diurnal variations of esophageal motor function in children using combined ambulatory 24‐hour esophageal manometry and continuous intraluminal pH measurement (MP24).

Methods

Medical records of all patients referred for the performance of MP24 from 1995 to 2002 at a tertiary care center were reviewed. Patients were selected retrospectively for this study using the following inclusion criteria: (1) no dysphagia, (2) normal upper gastrointestinal barium radiograph, (3) normal esophagogastroduodenoscopy and biopsies, (4) normal stationary esophageal manometry, (5) normal esophageal pH probe, and (6) no gastrointestinal pathology appearing after long‐term follow‐up. Data from the MP24 of these children were retrospectively analyzed for differences between meal, upright, and supine periods using nonparametric univariate analysis.

Results

One hundred twenty‐three children had MP24 during the study period. Eleven met the criteria for normality and were included. Their mean age was 12.4 ± 1.5 years. The number of contractions/minute in the upper, middle, and lower esophageal body differed significantly during meals and in the upright and supine periods (P < 0.01). A significant increase in motor activity occurred during meals (P < 0.01). There was less motor activity observed in the supine position than in the upright position (P < 0.01). There were significant differences in effective (P < 0.05) and total propagated peristalsis among the meal, upright, and supine periods (P < 0.01), with the largest percentage of propagated contractions observed during meals.

Conclusion

This study provides the first information on prolonged esophageal motor activity in pediatric patients without esophageal disease. MP24 in children demonstrates significant diurnal variations in esophageal motor function that is similar to the findings in studies of healthy adults.
Anti‐Inflammatory and Growth‐Stimulating Effects Precede Nutritional Restitution During Enteral Feeding in Crohn Disease
Authors: Bannerjee Kaushik , Camacho‐Hübner Cecilia , Babinska Katarzyna , Dryhurst Kay M. , Edwards Ray , Savage Martin O. , Sanderson Ian R. , Croft Nicholas M.
Published: January 2024

Objectives

Exclusive enteral feeding reduces inflammation and improves well being, nutrition and growth in children with active Crohn disease. Whether improved growth and increases in growth‐related proteins are a consequence of improved nutrition or a reduced inflammation is not known. This study was undertaken to test the hypothesis that changes in growth‐related proteins are related to decreased inflammation, rather than improvement in nutritional status.

Methods

Twelve children with active Crohn disease treated for 6‐weeks with exclusive enteral feeding were studied at days 0, 3, 7, 14, 21, 28, and 56. The Paediatric Crohn's Disease Activity Index (PCDAI), weight, triceps skinfold thickness, and midupper arm circumference were recorded. C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin‐6 (IL‐6), insulin‐like growth factor (IGF‐I), IGF‐binding protein (IGFBP‐3), and leptin were measured at each visit. Wilcoxon matched‐pairs signed‐rank test was used to compare day 0 with follow‐up data.

Results

Significant improvements (P < 0.05) occurred by day 3 in inflammatory parameters (ESR, IL‐6) and by day 7 in PCDAI, CRP, and IGF‐I. These changes preceded any significant changes in nutritional parameters (weight‐for‐age Z score and midupper arm circumference day 14, triceps skinfold thickness day 21).

Conclusions

Early increases in IGF‐I during treatment of Crohn disease are attributable to the anti‐inflammatory effect of the enteral feed rather than nutritional restitution.
Acidified Milk Formula Supplemented With Bifidobacterium lactis: Impact on Infant Diarrhea in Residential Care Settings
Authors: Chouraqui Jean‐Pierre , Van Egroo Louis‐Dominique , Fichot Marie‐Claire
Published: January 2024

Objectives

Probiotics may be useful in preventing acute infectious diarrhea. Bifidobacteria are particularly attractive as probiotics agent because they constitute the predominant colonic flora of breastfed infants and are thought to play a role in the decreased incidence of diarrhea in breastfed infants.

Methods

This was a multicenter, double‐blind, controlled study to evaluate the efficacy of a milk formula supplemented with viable Bifidobacterium lactis strain Bb 12 (BbF) in the prevention of acute diarrhea in infants younger than 8 months living in residential nurseries or foster care centers.

Results

Ninety healthy children received either the BbF or a conventional formula (CF) daily. The mean duration of the stay in the residential center was similar (137 v 148 days). At enrollment, there were no differences between the two groups with respect to age (3.7 ± 2.1 months), gender, anthropometric data, history of allergy or gastrointestinal disease, frequency of breast‐feeding in the neonatal period or timing of introduction of solid food. Altogether, 28.3% of the BbF infants had diarrhea during the study compared with 38.7% of controls (NS). There was a statistically insignificant trend for shorter episodes of diarrhea in the BbF group (5.1 ± 3.3 days v 7 ± 5.5 days, NS). The number of days with diarrhea was 1.15 ± 2.5 in the BbF group with a daily probability of diarrhea of 0.84 versus 2.3 ± 4.5 days and 1.55, respectively, in the CF group (P = 0.0002 and 0.0014). Feeding infants with the BbF reduced their risk of getting diarrhea by a factor of 1.9 (range, 1.33–2.6). Analysis of the cumulative incidence of diarrheal episodes showed a trend that the first onset of diarrhea occurred later in the BbF group.

Conclusion

These results provide some evidence that viable Bifidobacterium lactis strain Bb 12, added to an acidified infant formula, has some protective effect against acute diarrhea in healthy children.
Prenatal Stress Alters Bacterial Colonization of the Gut in Infant Monkeys
Authors: Bailey Michael T. , Lubach Gabriele R. , Coe Christopher L.
Published: January 2024

Objective:

The hypothesis that prenatal stress lowers the levels of protective microflora and increases the risk for postpartum Gram‐negative pathogens was tested in infant monkeys.

Methods:

Female monkeys were left undisturbed or were stressed during pregnancy using an acoustical startle paradigm for 6 weeks either early or late in their 24‐week gestation. Several types of intestinal microflora were repeatedly enumerated by fecal culture while infants were reared normally by their mothers.

Results:

Significant changes in microflora concentrations occurred during the first 6 months of life. The profile of total aerobes and facultative anaerobes was biphasic, with peak concentrations occurring between 2 and 16 weeks of age. The numbers of bifidobacteria and lactobacilli were low at 2 days after birth but rapidly increased to a peak between 8 and 16 weeks of age. Although similar temporal patterns were evident in all infants, prenatal stress reduced the overall numbers of bifidobacteria and lactobacilli.

Conclusions:

Moderate disturbance during pregnancy was sufficient to alter the intestinal microflora in the newborn infant. These alterations could result in enhanced susceptibility to infection and suggest a mechanism for some effects of maternal pregnancy conditions on infant health.
Helicobacter pylori Eradication Rate and Glycemic Control in Young Patients With Type 1 Diabetes
Authors: Candelli Marcello , Rigante Donato , Marietti Giovanni , Nista Enrico C. , Crea Francesca , Schiavino Alessandra , Cammarota Giovanni , Pignataro Giulia , Petrucci Stefano , Gasbarrini Giovanni , Gasbarrini Antonio
Published: January 2024

Objectives:

Eradication of Helicobacter pylori is more difficult in adult patients with diabetes than in patients with dyspepsia. It has also been suggested that eradication of H. pylori in children with type 1 diabetes mellitus improves their metabolic control. The aim of the current study was to assess the eradication rate of a standard triple therapy and its effects on glycemic control in young patients with type 1 diabetes.

Methods:

The authors enrolled 29 type 1 diabetic patients with H. pylori, 29 type 1 diabetic patients without H. pylori, and 29 dyspeptic children with H. pylori. Groups were matched for gender and age and had similar geographical origin and socioeconomic status. H.pylori status was investigated before and 6 weeks after therapy by 13C‐urea breath test. All enrolled patients with H. pylori were prescribed a standard triple therapy for eradicating H. pylori. Glycosylated hemoglobin A and daily insulin requirement were evaluated at enrollment and 6 months later in all patients with diabetes. The prevalence of the most common gastrointestinal symptoms also was investigated by means of a questionnaire in all subjects at enrollment and 6 months later.

Results:

Eradication of H. pylori was similar in patients with diabetes (24/29) and those with dyspepsia (23/29) (83%v 79%; P = NS). No difference in metabolic control was observed before or after antibiotic treatment in the patients who experienced H. pylori eradication. No difference in glycemic control was observed after 6 months of follow‐up.

Conclusions:

The eradication rate of H. pylori infection was similar for young patients with type 1 diabetes and those with dyspepsia and did not improve metabolic control in a short‐term follow‐up.
Association of Schatzki Ring With Eosinophilic Esophagitis in Children
Authors: Nurko Samuel , Teitelbaum Jonathan E. , Husain Khaled , Buonomo Carlo , Fox Victor L. , Antonioli Donald , Fortunato Christine , Badizadegan Kamran , Furuta Glenn T.
Published: January 2024

Objective:

To describe the clinicopathologic characteristics of children with Schatzki ring and to determine if Schatzki ring is associated with eosinophilic esophagitis.

Methods:

The authors report 18 adolescents with radiographically diagnosed Schatzki ring (SR). Their clinical and histologic characteristics were reviewed in a blinded fashion.

Results:

The mean age of the patients was 15.8 ± 0.8 years and mean duration of symptoms was 2.6 ± 0.4 years. By histologic criteria, two groups of patients were defined. Eight had clinical and histologic criteria of eosinophilic esophagitis (EE) and 10 of peptic esophagitis. There were no differences in the symptoms or radiographic findings in the two groups. The SR was not identified by endoscopy in any EE patient and was identified in 70% of peptic esophagitis patients. Grossly apparent mucosal features associated with EE were significantly more common in those with EE. Those with peptic esophagitis had a significantly higher acid exposure than did those with EE (12.6 ± 2.9 v 2.0 ± 1.1%; P < 0.01) by esophageal pH probe. Patients with peptic esophagitis responded to proton pump inhibitors and/or dilatation, whereas those with EE did not have good response and required specific therapy for EE.

Conclusions:

EE may play a role in the pathogenesis of some patients with SR.
Developmental Pharmacokinetics and Pharmacodynamics of Nizatidine
Authors: Abdel‐Rahman Susan M. , Johnson Franklin K. , Connor James D. , Staiano Annamaria , Dupont Christophe , Tolia Vasundhara , Winter Harland , Gauthier‐Dubois Ginette , Kearns Gregory L.
Published: January 2024

Objectives:

To characterize the impact of development on the pharmacokinetics and pharmacodynamics of nizatidine.

Methods:

Children (age range, 5 days–18 years) and adults (age range, 18–50 years) were enrolled in four open‐label trials. Nizatidine formulation and dose were determined by age: infants received 2 or 4 mg/kg IV, children 2.5 or 5 mg/kg in one of three oral liquid formulations, and adolescents and adults received a fixed 150‐mg capsule. Nizatidine and N‐desmethylnizatidine concentrations were measured in serial post‐dose plasma samples by a high‐performance liquid chromatographic assay with mass spectrometric detection. Intragastric pH was recorded during a 24‐hour post‐dose interval.

Results:

Data on 93 subjects were combined with previous values from 36 individuals to cover an age group not adequately captured and to control for formulation effects. Dose‐normalized exposure estimates revealed no apparent age dependence; however, maximum plasma concentration (298.5 ± 100.7 v 552.8 ± 152.4 ng/mL per mg/kg dose) and AUC0‐∞ (954.4 ± 379.8 v 1,573.0 ± 347.4 ng*hour/mL per mg/kg dose) were reduced in extemporaneous formulations in apple juice. The apparent modest age dependence observed for total body clearance (Cl/F) (r2 = 0.365) and Vss/F (r2 = 0.221) reflected a formulation‐dependent decrease in bioavailability rather than a true age effect. The age‐associated changes in λz observed for nizatidine and its metabolite were predictable and consistent with developmental acquisition of renal function. Mean and median pH, as well as fraction of time that the dosing interval remained above target pH values, were significantly greater with administration of the drug than without.

Conclusions:

The biodisposition of nizatidine in children and adults is similar; however, response after a comparable weight‐based dose is equal and potentially greater in children.
Innate Immunity of the Gut: Mucosal Defense in Health and Disease
Authors: Yuan Qian , Walker W. Allan
Published: January 2024

The intestine is an important immune organ consisting of a complex cellular network, secreted peptides and proteins and other host defenses. Innate immunity plays a central role in intestinal immune defense against invading pathogens. It also serves as a bridge to the activation of the adaptive immune system. Pattern recognition molecules of microorganisms are an essential component for identifying invading pathogens. Toll‐like receptors (TLRs), CARD15/NOD2 and scavenger receptors all serve as the pattern recognition receptors in the innate immune defense system. Secreted bactericidal peptides or defensins produced by the intestinal epithelia represent another crucial element of innate mucosal immune defense. Mutations in pattern recognition receptors and dysfunction of secretory bactericidal peptides may impair host immune defenses leading to an invasion of pathogens resulting in chronic inflammation of the gut. This review updates our current understanding of innate immunity of the gastrointestinal tract.
Malnutrition: Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition
Authors: Fuchs George , Ahmed Tahmeed , Araya Magdalena , Baker Susan , Croft Nick , Weaver Lawrence
Published: January 2024

Research

Protocolized management of malnutrition.

Prevention and management of low birth weight.

Micronutrients.

Intervention

Promote universal application of WHO guidelines for inpatient treatment of severe malnutrition.

Establish a system for the nutritional assessment and management of hospitalized children.

Implement national programs to encourage proper infant feeding and to prevent malnutrition.

Education

Rehabilitation diets for the treatment of severely malnourished children using locally available foods.

Infant feeding practices.
Effects of Protein Deprivation on Growth and Small Intestine Morphology Are Not Improved By Glutamine or Glutamate in Gastrostomy‐Fed Rat Pups
Authors: Li Nan , Lassman Beth J. , Liu Zhiwei , Liboni Kellym , Neu Josef
Published: January 2024

Objectives:

Critically ill neonates often have their enteral intake severely limited shortly after birth. Whether glutamine (Gln) or glutamate (Glu) can preserve intestinal structure and function in the neonate undergoing limited enteral feeding is not clear. We hypothesize that Gln and Glu can similarly preserve intestinal structure in the developing small intestine of infant rats fed a low protein diet.

Methods:

Using a gastrostomy‐fed “pup‐in‐a‐cup” rat model, the effects of Gln and Glu on the developing rat small intestine were examined. Four groups of 6‐ to 7‐day‐old pups were fed rat milk substitute (RMS) via gastrostomy tube. One group was provided 100% and three were provided 25% of the protein normally received from their mothers. Two of the groups fed 25% protein received additional Gln or Glu for 6 days.

Results:

Pups receiving the 100% protein RMS were larger than pups receiving the 25% protein RMS with or without Gln/Glu supplementation (P < 0.001). Average villus height (P < 0.01) and area (P < 0.01) were greater in pups receiving 100% protein RMS than in pups given 25% protein RMS formula. There was no significant difference among the groups in mucosal maltase or alkaline phosphatase activities. Tight junction protein claudin‐1 was significantly higher in the group fed 100% protein RMS diet, while occludin did not differ among the 4 groups. Neither Gln nor Glu increased claudin‐1 or occludin in rats fed 25% protein.

Conclusions:

These results suggest that neither Gln nor Glu supplementation can substitute effectively for whole protein in the developing rat small intestine for the outcomes that were evaluated.
Mucous Fistula Refeeding in Premature Neonates With Enterostomies
Authors: Wong Kenneth K. Y. , Lan Laurence C. L. , Lin Steve C. L. , Chan Audrey W. S. , Tam Paul K. H.
Published: January 2024

Background:

Premature neonates with short bowel syndrome often have diverting enterostomies and distal mucous fistulae. The authors reviewed their experience in 12 premature neonates in whom proximal bowel contents were re‐fed into the mucous fistula.

Methods:

We reviewed the records of 12 premature neonates who presented with acute abdomen and who underwent intestinal resection with formation of diverting enterostomy and mucous fistula between July 1999 and December 2002. All received parenteral nutrition. Refeeding of enterostomy contents into the distal mucous fistula was commenced after patency of the distal intestine was confirmed by radiologic examination. Demographic data, body weight and clinical outcomes were recorded.

Results:

Median gestational age was 31 weeks and mean birth weight was 1.59 kg. Diagnoses included necrotizing enterocolitis (n = 6), meconium ileus–like conditions (n = 2), ileal atresia (n = 2), malrotation with volvulus (n = 1) and focal intestinal perforation (n = 1). Refeeding was successfully established in all patients with no complications. The mean duration of refeeding was 63.5 days. All patients achieved good weight gain after refeeding (18.9 ± 2.9 g/d) with a reduction of parenteral nutrition requirements. All enterostomies were subsequently closed. Four patients died of unrelated causes after reanastomosis and the remaining eight were discharged.

Conclusions:

Mucous fistula refeeding is safe in premature neonates with enterostomies. It can prevent disuse atrophy in the distal loop and facilitate subsequent reanastomosis. Furthermore, the increased absorptive function provided by the small bowel incorporated in the mucous fistula can reduce the requirement for total parenteral nutrition.
Associations between externalizing behavior problems and risky sexual behaviors in adolescence: Attachment as a mediator
Authors: Therriault Danyka , Lemelin Jean‐Pascal , Toupin Jean , Martin‐Storey Alexa , Déry Michèle
Published: January 2024

Introduction

Risky sexual behaviors in adolescence are associated with negative health and psychological functioning outcomes. Although the association between behavior problems and risky sexual behaviors is well established, addressing these problems requires understanding the mechanisms that help explain this association. Adolescent attachment, while related to risky sexual behavior, has not been extensively explored as an outcome of childhood externalizing problems. The two objectives of this study were to explore the links between parental and peer attachment and risky sexual behaviors and to examine the mediating effect of attachment on the links between behavior problems and risky sexual behaviors.

Methods

Five hundred and ninety‐eight French‐Canadian adolescents (46.2% girls), Mage at T1 = 13.23; Mage at T2 = 14.28; Mage at T3 = 17.35) participated in this longitudinal study.

Results

The quality of parental attachment at T2 was significantly and negatively associated with risky sexual behaviors 3 years later, at T3. More specifically, a lower quality parental attachment relationship was associated with having nonexclusive partners as well as with inconsistent condom use. Finally, parental attachment (T2) was a significant mediator between behavior problems (T1) and risky sexual behaviors (T3), but only for younger adolescents.

Conclusions

Findings suggest that in addition to behavior problems in adolescence, the quality of parental attachment relationships may help in understanding risky sexual behaviors in adolescence.
Identification of fourth‐instar larvae of Aedes albopictus (Skuse) (Diptera: Culicidae) employing scanning electron microscopic tool
Authors: Yamany Abeer S. , Abdel‐Gaber Rewaida
Published: January 2024

Aedes albopictus is a vector of numerous viruses in tropical and subtropical regions worldwide, including encephalitis and dengue fever. Although the identification keys depend exclusively on the characteristics of the fourth larval instar, the studies were carried out using scanning electron microscopy (SEM) on the morphology of Ae. albopictus are still insufficient, and more research is required. Therefore, the purpose of this study was to present a comprehensive description of Ae. albopictus mosquitoes based on the morphological features of their fourth‐instar larvae to distinguish them from other mosquito species. Antennae, feeding mouth brushes, mandibles, maxillae, labia, comb scales, anal papillae, siphon, respiratory spiracles, and pecten teeth were among the morphological features specifically described using SEM. The sensilla trichoidea and the sensilla basiconica are the sensory spicules found on the antennal integument. The labrum is a tessellated membrane with two movable brushes on the sides and one middle brush. The mandibles have four sellar setae on the anterolateral side, and the maxillae, which have a thumb‐like structure and a palp located laterally and about four‐fifths of the way from the maxillary brush base to the maxillary notch, are the articulating appendages. On the apex of the palp, there are five sensilla. The eighth abdominal segment is a tiny pentagonal structure with 12 comb scales laterally and a respiratory siphon dorsally. The siphon has two rows of pectin teeth, with 12 teeth per row. Four pairs of siphonal tufts and five perispiracular lobes surround the respiratory spiracles. The anal segment has four anal papillae, a ventral brush, a dorsal brush, and an incomplete saddle. The findings demonstrate that the fourth‐instar larvae of Ae. albopictus have distinctive morphological features, which are crucial for understanding their key characteristics and identifying them, preventing inaccurate identification, and facilitating the control of diseases transmitted by the mosquito vector.

Research Highlights

A detailed description of various taxonomical interest structures for the fourth‐instar larvae of Aedes albopictus is included in this study.

Scanning electron microscopy is considered a helpful technique for identifying Ae. albopictus larvae in their fourth instar.
自己決定権について倫理的配慮を要した自殺企図によるアセトアミノフェン中毒の1例(A case of acetaminophen poisoning in a patient with suicidal ideations: ethical considerations regarding the right to self–determination)
Authors: 正幸 大田原 , 尚史 今長谷 , 尚一郎 濱田 , カシンスキー リチャード・ , 智継 中野 , 幹男 中島
Published: January 2024

アセトアミノフェンは比較的安全性の高い解熱鎮痛薬として，一般にも広く用いられているが，大量摂取により肝毒性を呈し，急性肝不全に至った場合は人工肝補助療法や肝移植が必要な場合もある。症例は65歳の女性，意識障害と痙攣を主訴に救急搬送された。病院到着後も症状が遷延し，血液検査で肝胆道系酵素の著明な上昇と腎機能障害を認めたが意識障害のため原因は不明であった。入院後アセトアミノフェン中毒が判明しN–アセチルシステインによる治療を行ったが急性肝不全が進行し，人工肝補助療法や肝移植が必要な状況と考えられた。侵襲的な医療処置はすべて拒否するという本人による事前指示があったため，臨床倫理委員会に判断を付託した結果，内科的加療は継続するが，患者の自己決定権に対する倫理的配慮を重んじて侵襲的治療は差し控えることとなり，第2病日に患者は死亡した。救急現場において，自殺を企図して過量服薬し重症化した際に，意識障害を呈する場合には精神障害の診断をつけることが難しく，医師の裁量権が重視され，侵襲的処置を望まないという患者の意思表示に配慮することは容易でない。十分な情報を得たうえで意思決定を下している事前指示がある場合，患者の自己決定権が尊重される場合もあり，倫理委員会などを通して，判断の妥当性を検討すべきだと考えられる。
Lysosomal storage disorders identified in adult population from India: Experience of a tertiary genetic centre and review of literature
Authors: Sheth Jayesh , Nair Aadhira , Bhavsar Riddhi , Godbole Koumudi , Datar Chaitanya , Nampoothiri Sheela , Panigrahi Inusha , Shah Heli , Bajaj Shruti , Tayade Naresh , Bhardwaj Naveen , Sheth Harsh
Published: January 2024

Lysosomal storage disorders (LSDs) in adults have milder phenotype and variable age at presentation. Several studies have described the phenotype, genotype and treatment outcomes for adult‐onset LSDs like Gaucher, Fabry, Pompe disease and others. We describe the first systematic study on the occurrence of LSDs in an adult population from India. It describes, the key clinical signs seen in these patients and those from literature review that can aid in early detection. Of 2102 biochemically diagnosed LSDs cases, 32 adult patients were identified with LSDs. Based on the clinical suspicion, screening test and enzyme study was carried out. Twenty‐two patients were subjected to a genetic study to identify the causative variant in a respective gene. Of the 32 adult patients, we observed a maximum percentage of 37.5% (n = 12) cases with Gaucher disease, followed by 13% (n = 4) with Fabry disease. We found 10% of cases with MPS IVA and MPS I, and 9% cases with Pompe. Single case of adult mucolipidosis III and two cases each of Type 1 Sialidosis, Niemann‐Pick disease B and metachromatic leukodystrophy were identified. We observed two common variants p.Leu483Pro and p.Ala487Thr in the GBA1 gene in 23% of Indian patients with adult Gaucher disease. No common variants were observed in other aforementioned LSDs. Study identified 50% of Fabry patients and 4% of Gaucher patients diagnosed at our centre to be adults. The prevalence of adult Pompe patients was low (3.4%) as compared to 80% reported in the Caucasian population. Adult LSDs such as, MPS III, GM1/GM2 gangliosidosis and Krabbe disease were not identified in our cohort.
Understanding the mechanisms underlying the disruption of the blood–brain barrier in parasitic infections
Authors: Jamil Al‐Obaidi Mazen M. , Desa Mohd Nasir Mohd
Published: January 2024

Parasites have a significant impact on the neurological, cognitive, and mental well‐being of humans, with a global population of over 1 billion individuals affected. The pathogenesis of central nervous system (CNS) injury in parasitic diseases remains limited, and prevention and control of parasitic CNS infections remain significant areas of research. Parasites, encompassing both unicellular and multicellular organisms, have intricate life cycles and possess the ability to infect a diverse range of hosts, including the human population. Parasitic illnesses that impact the central and peripheral nervous systems are a significant contributor to morbidity and mortality in low‐ to middle‐income nations. The precise pathways through which neurotropic parasites infiltrate the CNS by crossing the blood–brain barrier (BBB) and cause neurological harm remain incompletely understood. Investigating brain infections caused by parasites is closely linked to studying neuroinflammation and cerebral impairment. The exact molecular and cellular mechanisms involved in this process remain incomplete, but understanding the exact mechanisms could provide insight into their pathogenesis and potentially reveal novel therapeutic targets. This review paper explores the underlying mechanisms involved in the development of neurological disorders caused by parasites, including parasite‐derived elements, host immune responses, and modifications in tight junctions (TJs) proteins.
Advancing the methodology of mapping reviews: A scoping review
Authors: Khalil Hanan , Campbell Fiona , Danial Katrina , Pollock Danielle , Munn Zachary , Welsh Vivian , Saran Ashrita , Hoppe Dimi , Tricco Andrea C.
Published: January 2024

This scoping review aims to identify and systematically review published mapping reviews to assess their commonality and heterogeneity and determine whether additional efforts should be made to standardise methodology and reporting. The following databases were searched; Ovid MEDLINE, Embase, CINAHL, PsycINFO, Campbell collaboration database, Social Science Abstracts, Library and Information Science Abstracts (LISA). Following a pilot‐test on a random sample of 20 citations included within title and abstracts, two team members independently completed all screening. Ten articles were piloted at full‐text screening, and then each citation was reviewed independently by two team members. Discrepancies at both stages were resolved through discussion. Following a pilot‐test on a random sample of five relevant full‐text articles, one team member abstracted all the relevant data. Uncertainties in the data abstraction were resolved by another team member. A total of 335 articles were eligible for this scoping review and subsequently included. There was an increasing growth in the number of published mapping reviews over the years from 5 in 2010 to 73 in 2021. Moreover, there was a significant variability in reporting the included mapping reviews including their research question, priori protocol, methodology, data synthesis and reporting. This work has further highlighted the gaps in evidence synthesis methodologies. Further guidance developed by evidence synthesis organisations, such as JBI and Campbell, has the potential to clarify challenges experienced by researchers, given the magnitude of mapping reviews published every year.
Knockout of Shcbp1 sensitizes immunotherapy by regulating α‐SMA positive cancer‐associated fibroblasts
Authors: Gu Qianlin , Ma Zhijian , Wang Qiaoyan , Dai Yiwei , Shi Wengui , Jiao Zuoyi
Published: January 2024

The crucial role of cancer‐associated fibroblasts (CAFs) in promoting T‐cell exclusion has a significant impact on tumor immune evasion and resistance to immunotherapy. Therefore, enhancing T‐cell infiltration into solid tumors has emerged as a pivotal area of research. We achieved a conventional knockout of Shcbp1 (Shcbp1−/−) through CRISPR/Cas9 gene editing and crossed these mice with spontaneous breast cancer MMTV‐PyMT mice, resulting in PyMT Shcbp1−/− mice. The different CAF subtypes were detected by flow cytometry analysis (FCA). We evaluated collagen and CAFs levels using Sirius red staining, immunohistochemistry (IHC), and immunofluorescence (IF). Primary tumor cells and CAFs were isolated from both PyMT Shcbp1+/+ and PyMT Shcbp1−/− mice. We analyzed CAFs’ proliferation, invasion, migration, apoptosis, and cell cycle. Transwell coculture experiments were performed with primary tumor cells and CAFs to evaluate the role of CAFs in increasing the sensitivity of tumor cells to Erdafitinib. Tumors from PyMT Shcbp1+/+ and PyMT Shcbp1−/− mice were orthotopically transplanted to assess the therapeutic effect of the Erdafitinib and PD‐1 combination. CAFs and T‐cell infiltration in these tumors were assessed using FCA and IF. Knockout of Shcbp1 leads to a significant reduction in tumor burden, promotes longer survival, and decreases CAFs in MMTV‐PyMT. Moreover, knockout of Shcbp1 enhances the sensitivity of Erdafitinib, leading to effective inhibition of CAFs' proliferation and invasion, as well as the induction of apoptosis. Additionally, it results in cell cycle arrest at the G2/M phase in vitro. Meanwhile, Shcbp1−/− CAFs change the sensitivity of Shcbp1−/− tumor cells to Erdafitinib compared to Shcbp1+/+ CAFs. Importantly, knockout of Shcbp1 boosts the effectiveness of Erdafitinib in combination with immune checkpoint blockade therapy by augmenting T‐cell infiltration through CAFs regulation in vivo. Our findings demonstrate that knockout of Shcbp1 holds significant potential in enhancing the therapeutic response of Erdafitinib combined with PD‐1 antibody treatment, offering promising prospects for future breast cancer therapies.
Ultrathin and conformal frequency selective surfaces bandpass filter to eliminate the 5G bands on radio altimeters
Authors: Thulasiraman Jayanandan , Alex Zachariah C.
Published: January 2024

This work proposes a frequency‐selective surface‐based radome structure to selectively allow the radar altimeter operating band and also minimize the interference from Sub‐6GHz 5 G frequency bands. A Jerusalem cross and combinational loop (JCL) based frequency selective surfaces (FSS) unit cell of overall dimension 0.37λ was synthesized using a thin flexible substrate for use in fuselage of airborne systems. The proposed FSS unit cell exhibits transmission zero at 3.61 and 6.025 GHz and highly selective pass band at 4.3 GHz. The effect of bends and angle of incidence on the frequency response of the synthesized FSS was studied in transverse electric and transverse magnetic modes. A lumped element‐based equivalent circuit model for the proposed design was also presented. Finally, the fabricated prototype was experimentally validated in an Anechoic chamber setup and the suitability of the proposed FSS layers for aviation radar systems was confirmed.
A novel constitutive model for the concrete face slab of a CFRD and the numerical simulation of its seismic behavior
Authors: Xu Jianjun , Ning Zhiyuan , Wang Yingjun , Zhou Wei , Zhu Sheng
Published: January 2024

With the rising demand for hydropower energy, China has built numerous concrete‐faced rockfill dams (CFRDs) with considerable heights. The potential failure pattern of the concrete face slab is the key to the safety of the anti‐seepage system. However, engineers commonly employ an elastic relationship to model the concrete face slab for simplicity, which induces inaccurate estimation of the face slab's stresses, especially under seismic conditions. On the other hand, the existing elastoplastic models for concrete often require complex derivation of the necessary formula and thus are difficult to apply to finite element (FE) analysis. Under the comprehensive action of the upstream water, supporting rockfill, and surrounding mountains, the damage mode of the quasibrittle concrete slab is not a tensile mode but a compressive shearing mode. Therefore, it is urgent to establish an elastoplastic model that is adapted to the actual working environment of the slab and easy to apply. To this end, a generalized plasticity model is developed within the phenomenology modeling concept, which is validated at both the experimental level and application level. The results indicate that three‐dimensional stress‒strain behaviors, such as the strength nonlinearity, prepeak dilatancy, and postpeak softening, can be effectively captured. In addition, the seismic characteristics of a 200‐m high CFRD are numerically investigated. The findings show that the slab's stress accumulation can be reflected during the earthquake and that the final stress distribution conforms to the field observations. The conclusions of this paper provide a reliable reference for the seismic resistance design of CFRDs.
The effects of axonal beading and undulation on axonal diameter estimation from diffusion MRI: Insights from simulations in human axons segmented from three‐dimensional electron microscopy
Authors: Lee Hong‐Hsi , Tian Qiyuan , Sheft Maxina , Coronado‐Leija Ricardo , Ramos‐Llorden Gabriel , Abdollahzadeh Ali , Fieremans Els , Novikov Dmitry S. , Huang Susie Y.
Published: January 2024

The increasing availability of high‐performance gradient systems in human MRI scanners has generated great interest in diffusion microstructural imaging applications such as axonal diameter mapping. Practically, sensitivity to axon diameter in diffusion MRI is attained at strong diffusion weightings
, where the deviation from the expected
scaling in white matter yields a finite transverse diffusivity, which is then translated into an axon diameter estimate. While axons are usually modeled as perfectly straight, impermeable cylinders, local variations in diameter (caliber variation or beading) and direction (undulation) are known to influence axonal diameter estimates and have been observed in microscopy data of human axons. In this study, we performed Monte Carlo simulations of diffusion in axons reconstructed from three‐dimensional electron microscopy of a human temporal lobe specimen using simulated sequence parameters matched to the maximal gradient strength of the next‐generation Connectome 2.0 human MRI scanner (
500 mT/m). We show that axon diameter estimation is accurate for nonbeaded, nonundulating fibers; however, in fibers with caliber variations and undulations, the axon diameter is heavily underestimated due to caliber variations, and this effect overshadows the known overestimation of the axon diameter due to undulations. This unexpected underestimation may originate from variations in the coarse‐grained axial diffusivity due to caliber variations. Given that increased axonal beading and undulations have been observed in pathological tissues, such as traumatic brain injury and ischemia, the interpretation of axon diameter alterations in pathology may be significantly confounded.
The Use of Deep Learning Software in the Detection of Voice Disorders: A Systematic Review
Authors: Barlow Joshua , Sragi Zara , Rivera‐Rivera Gabriel , Al‐Awady Abdurrahman , Daşdöğen Ümit , Courey Mark S. , Kirke Diana N.
Published: January 2024

Objective

To summarize the use of deep learning in the detection of voice disorders using acoustic and laryngoscopic input, compare specific neural networks in terms of accuracy, and assess their effectiveness compared to expert clinical visual examination.

Data Sources

Embase, MEDLINE, and Cochrane Central.

Review Methods

Databases were screened through November 11, 2023 for relevant studies. The inclusion criteria required studies to utilize a specified deep learning method, use laryngoscopy or acoustic input, and measure accuracy of binary classification between healthy patients and those with voice disorders.

Results

Thirty‐four studies met the inclusion criteria, with 18 focusing on voice analysis, 15 on imaging analysis, and 1 both. Across the 18 acoustic studies, 21 programs were used for identification of organic and functional voice disorders. These technologies included 10 convolutional neural networks (CNNs), 6 multilayer perceptrons (MLPs), and 5 other neural networks. The binary classification systems yielded a mean accuracy of 89.0% overall, including 93.7% for MLP programs and 84.5% for CNNs. Among the 15 imaging analysis studies, a total of 23 programs were utilized, resulting in a mean accuracy of 91.3%. Specifically, the twenty CNNs achieved a mean accuracy of 92.6% compared to 83.0% for the 3 MLPs.

Conclusion

Deep learning models were shown to be highly accurate in the detection of voice pathology, with CNNs most effective for assessing laryngoscopy images and MLPs most effective for assessing acoustic input. While deep learning methods outperformed expert clinical exam in limited comparisons, further studies integrating external validation are necessary.