Background: Obesity affects nearly a billion people globally and is associated with various health consequences.Current anti-obesity medications primarily target appetite, but drug candidates that modulate energy expenditure (EE) and substrate utilization based on respiratory exchange ratio (RER) are also essential to continuously improve the treatment modalities for people living with obesity. Selecting appropriate animal models and methods is crucial to improving translational value in preclinical research. While pig obesity models provide a relevant alternative to rodent models due to their similarities to humans, little is known about the assessment and translatability of EE in pigs. The aim of this study was to evaluate the translatability of minipigs for assessing the effect of EE-modulating drugs using indirect calorimetry and three positive control compounds that have known effects on EE and/or RER in humans. The study consisted of five sub-studies: Sub-study 1 assessed EE and RER based on sex (male/female) and diet (chow/high-fat diet) with and without correction for body composition; Sub-studies 2–4 evaluated changes in EE and RER after treatment with three positive control compounds: 2,4-dinitrophenol, DNP; a glucagon receptor agonist, GCG-RA; and a melanocortin receptor 4 agonist, MC4-RA; and sub-study 5 established three predictive equations for resting metabolic rate. Results: Sub-study 1 resulted in detectable differences in EE and RER based on diet/body sizes (P-value < 0.0001), while EE adjusted for body composition resulted in differences based on sex (P-value < 0.0001). Sub-studies 2–4 revealed that the three pharmacological interventions known to affect EE in humans, DNP, GCG-RA, and MC4-RA, showed similar effects in the Göttingen Minipigs by significantly increasing EE by 26.1% (P-value: 0.0014), 21.3% (P-value: 0.0491), and 25.4% (P-value: 0.0013), respectively, emphasizing the translational value of the model. In substudy 5, three predictive equations were established for RMR based on body composition, demographic and anthropometric measurements, and the most accurate equation based on all variables. All three equations demonstrated acceptable accuracy (adjusted ­R2 : 0.73–0.85). Conclusions The present study qualifies the use of Göttingen Minipigs for investigating EE in preclinical research and provides a framework for conducting such research.

Background: Obesity affects nearly a billion people globally and is associated with various health consequences.Current anti-obesity medications primarily target appetite, but drug candidates that modulate energy expenditure (EE) and substrate utilization based on respiratory exchange ratio (RER) are also essential to continuously improve the treatment modalities for people living with obesity. Selecting appropriate animal models and methods is crucial to improving translational value in preclinical research. While pig obesity models provide a relevant alternative to rodent models due to their similarities to humans, little is known about the assessment and translatability of EE in pigs. The aim of this study was to evaluate the translatability of minipigs for assessing the effect of EE-modulating drugs using indirect calorimetry and three positive control compounds that have known effects on EE and/or RER in humans. The study consisted of five sub-studies: Sub-study 1 assessed EE and RER based on sex (male/female) and diet (chow/high-fat diet) with and without correction for body composition; Sub-studies 2–4 evaluated changes in EE and RER after treatment with three positive control compounds: 2,4-dinitrophenol, DNP; a glucagon receptor agonist, GCG-RA; and a melanocortin receptor 4 agonist, MC4-RA; and sub-study 5 established three predictive equations for resting metabolic rate. Results: Sub-study 1 resulted in detectable differences in EE and RER based on diet/body sizes (P-value < 0.0001), while EE adjusted for body composition resulted in differences based on sex (P-value < 0.0001). Sub-studies 2–4 revealed that the three pharmacological interventions known to affect EE in humans, DNP, GCG-RA, and MC4-RA, showed similar effects in the Göttingen Minipigs by significantly increasing EE by 26.1% (P-value: 0.0014), 21.3% (P-value: 0.0491), and 25.4% (P-value: 0.0013), respectively, emphasizing the translational value of the model. In substudy 5, three predictive equations were established for RMR based on body composition, demographic and anthropometric measurements, and the most accurate equation based on all variables. All three equations demonstrated acceptable accuracy (adjusted ­R2 : 0.73–0.85). Conclusions The present study qualifies the use of Göttingen Minipigs for investigating EE in preclinical research and provides a framework for conducting such research.

Background: Obesity affects nearly a billion people globally and is associated with various health consequences.Current anti-obesity medications primarily target appetite, but drug candidates that modulate energy expenditure (EE) and substrate utilization based on respiratory exchange ratio (RER) are also essential to continuously improve the treatment modalities for people living with obesity. Selecting appropriate animal models and methods is crucial to improving translational value in preclinical research. While pig obesity models provide a relevant alternative to rodent models due to their similarities to humans, little is known about the assessment and translatability of EE in pigs. The aim of this study was to evaluate the translatability of minipigs for assessing the effect of EE-modulating drugs using indirect calorimetry and three positive control compounds that have known effects on EE and/or RER in humans. The study consisted of five sub-studies: Sub-study 1 assessed EE and RER based on sex (male/female) and diet (chow/high-fat diet) with and without correction for body composition; Sub-studies 2–4 evaluated changes in EE and RER after treatment with three positive control compounds: 2,4-dinitrophenol, DNP; a glucagon receptor agonist, GCG-RA; and a melanocortin receptor 4 agonist, MC4-RA; and sub-study 5 established three predictive equations for resting metabolic rate. Results: Sub-study 1 resulted in detectable differences in EE and RER based on diet/body sizes (P-value < 0.0001), while EE adjusted for body composition resulted in differences based on sex (P-value < 0.0001). Sub-studies 2–4 revealed that the three pharmacological interventions known to affect EE in humans, DNP, GCG-RA, and MC4-RA, showed similar effects in the Göttingen Minipigs by significantly increasing EE by 26.1% (P-value: 0.0014), 21.3% (P-value: 0.0491), and 25.4% (P-value: 0.0013), respectively, emphasizing the translational value of the model. In substudy 5, three predictive equations were established for RMR based on body composition, demographic and anthropometric measurements, and the most accurate equation based on all variables. All three equations demonstrated acceptable accuracy (adjusted ­R2 : 0.73–0.85). Conclusions The present study qualifies the use of Göttingen Minipigs for investigating EE in preclinical research and provides a framework for conducting such research.

Background: Obesity affects nearly a billion people globally and is associated with various health consequences.Current anti-obesity medications primarily target appetite, but drug candidates that modulate energy expenditure (EE) and substrate utilization based on respiratory exchange ratio (RER) are also essential to continuously improve the treatment modalities for people living with obesity. Selecting appropriate animal models and methods is crucial to improving translational value in preclinical research. While pig obesity models provide a relevant alternative to rodent models due to their similarities to humans, little is known about the assessment and translatability of EE in pigs. The aim of this study was to evaluate the translatability of minipigs for assessing the effect of EE-modulating drugs using indirect calorimetry and three positive control compounds that have known effects on EE and/or RER in humans. The study consisted of five sub-studies: Sub-study 1 assessed EE and RER based on sex (male/female) and diet (chow/high-fat diet) with and without correction for body composition; Sub-studies 2–4 evaluated changes in EE and RER after treatment with three positive control compounds: 2,4-dinitrophenol, DNP; a glucagon receptor agonist, GCG-RA; and a melanocortin receptor 4 agonist, MC4-RA; and sub-study 5 established three predictive equations for resting metabolic rate. Results: Sub-study 1 resulted in detectable differences in EE and RER based on diet/body sizes (P-value < 0.0001), while EE adjusted for body composition resulted in differences based on sex (P-value < 0.0001). Sub-studies 2–4 revealed that the three pharmacological interventions known to affect EE in humans, DNP, GCG-RA, and MC4-RA, showed similar effects in the Göttingen Minipigs by significantly increasing EE by 26.1% (P-value: 0.0014), 21.3% (P-value: 0.0491), and 25.4% (P-value: 0.0013), respectively, emphasizing the translational value of the model. In substudy 5, three predictive equations were established for RMR based on body composition, demographic and anthropometric measurements, and the most accurate equation based on all variables. All three equations demonstrated acceptable accuracy (adjusted ­R2 : 0.73–0.85). Conclusions The present study qualifies the use of Göttingen Minipigs for investigating EE in preclinical research and provides a framework for conducting such research.

Background: Obesity affects nearly a billion people globally and is associated with various health consequences.Current anti-obesity medications primarily target appetite, but drug candidates that modulate energy expenditure (EE) and substrate utilization based on respiratory exchange ratio (RER) are also essential to continuously improve the treatment modalities for people living with obesity. Selecting appropriate animal models and methods is crucial to improving translational value in preclinical research. While pig obesity models provide a relevant alternative to rodent models due to their similarities to humans, little is known about the assessment and translatability of EE in pigs. The aim of this study was to evaluate the translatability of minipigs for assessing the effect of EE-modulating drugs using indirect calorimetry and three positive control compounds that have known effects on EE and/or RER in humans. The study consisted of five sub-studies: Sub-study 1 assessed EE and RER based on sex (male/female) and diet (chow/high-fat diet) with and without correction for body composition; Sub-studies 2–4 evaluated changes in EE and RER after treatment with three positive control compounds: 2,4-dinitrophenol, DNP; a glucagon receptor agonist, GCG-RA; and a melanocortin receptor 4 agonist, MC4-RA; and sub-study 5 established three predictive equations for resting metabolic rate. Results: Sub-study 1 resulted in detectable differences in EE and RER based on diet/body sizes (P-value < 0.0001), while EE adjusted for body composition resulted in differences based on sex (P-value < 0.0001). Sub-studies 2–4 revealed that the three pharmacological interventions known to affect EE in humans, DNP, GCG-RA, and MC4-RA, showed similar effects in the Göttingen Minipigs by significantly increasing EE by 26.1% (P-value: 0.0014), 21.3% (P-value: 0.0491), and 25.4% (P-value: 0.0013), respectively, emphasizing the translational value of the model. In substudy 5, three predictive equations were established for RMR based on body composition, demographic and anthropometric measurements, and the most accurate equation based on all variables. All three equations demonstrated acceptable accuracy (adjusted ­R2 : 0.73–0.85). Conclusions The present study qualifies the use of Göttingen Minipigs for investigating EE in preclinical research and provides a framework for conducting such research.

INTRODUCTIONAlthough a majority of ingested foreign bodies (FBs) pass down the gastrointestinal tract spontaneously, those that are sharp, pointed or large in size need removal to avert serious complications. We highlight the urgent need and utility of endoscopic accessories and technical artistry in safe retrieval of FBs in children.

CLINICAL PICTUREFour children had accidentally swallowed a nail, metallic dumbbell, open safety pin and a cushion pin respectively. They were symptom-free and the abdominal plain radiographs revealed foreign body in the stomach in all the cases.

TREATMENTOesophago-gastro-duodenoscopy (OGD) was done in all the patients and could retrieve the nail, metallic dumbbell and open safety pin successfully using a Dormia basket, a polypectomy snare and a pair of rat-tooth forceps respectively. The cushion pin had migrated to the duodeno-jejunal junction within 4 hours of ingestion and necessitated open duodenotomy and retrieval.

OUTCOMEAll patients did well after the procedure with no complications.

CONCLUSIONSSwallowed FBs with pointed or sharp ends or large enough to cross the pylorus and duodenal sweep need removal and in the majority of the cases they can be retrieved by OGD. Sharp or pointed FBs that have crossed the second part of the duodenum necessitate urgent laparotomy for retrieval to prevent complications.

Adolescent ; Child ; Child, Preschool ; Deglutition ; Endoscopy, Gastrointestinal ; Female ; Foreign Bodies ; diagnosis ; etiology ; Humans ; Infant ; Male

In the absence of a neonatal intensive care unit (NICU) and total parenteral nutrition (TPN) gastroschisis management is challenging (1). If surgical closure is not done within the first 6 hours post partum, impending complications intervene, which then prevent a good outcome in such infants. The defect near the right side of the umbilicus provides the avenue for the intra-abdominal contents to protrude into the amniotic cavity in intra-uterine life and visceral exposure to the external environment increases the morbidity after delivery. The tight 2.5-5 cm bottleneck diameter provides further complications if not surgically corrected immediately. The prognosis has improved over the years and in well-set-up hospitals more than 95% have survived. Appropriate antenatal diagnosis (2) and early neonatal surgical intervention have improved the survival of these neonates. Blood investigation to assist with the antenatal diagnosis, such as amniotic fluid beta-endorphin analysis (3) and alpha-fetoprotein, assists in anticipating severe complications. Prevention of complications such as mesenteric infarct, fluid and electrolyte imbalance, necrotizing enterocolitis (NEC) and raised intra-abdominal compartment syndrome (RIACS) (2) and providing nutritional support have resulted in the good outcome of these cases. In the absence of accurate radiological diagnosis and back-up support services such as NICU and TPN, it is challenging to manage such infants. In a country where subspecialties are lacking it is very difficult to reassure the parents of a gastroschisis patient. Most of them do not make it. The following two case reports highlight some of these limitations and the alternative measures that can be taken to address the issues.