Investigating the Mechanisms Underlying U46619-Induced Contraction on Porcine Lower Esophageal Sphincter.

Gastroesophageal reflux disease (GERD) is associated with an incompetent lower esophageal sphincter (LES), resulting in the reflux of gastric contents into the esophagus. U46619, a thromboxane A2 (TXA2) receptor agonist, induces contractions in various smooth muscles. Therefore, this study aimed to investigate the effects and mechanisms of action of U46619 on the porcine LES. To achieve this, contractions of the clasp and sling strips of the porcine LES, induced by U46619, were measured using isometric transducers. Furthermore, the contractile mechanism of U46619 in the porcine LES was investigated by pretreating the strips with atropine (a muscarinic receptor antagonist), tetrodotoxin (a neuronal sodium channel blocker), nifedipine (a calcium channel blocker), and Ca2+-free Krebs-Henseleit solution. Additionally, reverse transcription polymerase chain reaction (PCR) and immunohistochemistry (IHC) were performed to determine the presence of the TXA2 receptor in porcine LES. The results of this study demonstrated that U46619 caused marked concentration-dependent contractions in both porcine sling and clasp strips. The mechanism of U46619-induced contraction of the porcine LES was found to be related to calcium channels. Furthermore, the reverse transcription PCR analysis and IHC revealed that the TXA2 receptor was expressed in the clasp and sling fibers of porcine LES. Consequently, this study suggests that U46619 mediates the contraction of porcine LES through calcium channels and has potential as a therapeutic approach for treating GERD. SIGNIFICANCE STATEMENT: This study establishes that U46619 induces concentration-dependent contractions in porcine LES, primarily mediated by calcium channels. The presence of the TXA2 receptor in LES clasp and sling fibers is confirmed. These findings highlight U46619's potential as a GERD therapeutic by targeting calcium channels for LES contraction modulation.

The Reduced Gut Lachnospira Species Is Linked to Liver Enzyme Elevation and Insulin Resistance in Pediatric Fatty Liver Disease.

The objective of this study was to investigate gut dysbiosis and its metabolic and inflammatory implications in pediatric metabolic dysfunction-associated fatty liver disease (MAFLD). This study included 105 children and utilized anthropometric measurements, blood tests, the Ultrasound Fatty Liver Index, and fecal DNA sequencing to assess the relationship between gut microbiota and pediatric MAFLD. Notable decreases in Lachnospira spp., Faecalibacterium spp., Oscillospira spp., and Akkermansia spp. were found in the MAFLD group. Lachnospira spp. was particularly reduced in children with MAFLD and hepatitis compared to controls. Both MAFLD groups showed a reduction in flavone and flavonol biosynthesis sequences. Lachnospira spp. correlated positively with flavone and flavonol biosynthesis and negatively with insulin levels and insulin resistance. Body weight, body mass index (BMI), and total cholesterol levels were inversely correlated with flavone and flavonol biosynthesis. Reduced Lachnospira spp. in children with MAFLD may exacerbate insulin resistance and inflammation through reduced flavone and flavonol biosynthesis, offering potential therapeutic targets.

Unnecessary radiation exposure during diagnostic radiography in infants in a neonatal intensive care unit: a retrospective cohort study.

Unnecessary radiation exposure (URE) during radiographic examination is an issue among infants in neonatal intensive care units (NICUs). The causes of URE have not been fully explored. This study investigated the incidence and identified the causes of URE in infants during diagnostic radiography in a NICU. This was a retrospective cohort study. We retrieved and analysed requests and radiographs taken at a tertiary NICU between September and November 2018. URE was defined as the rate of discordance between requests and images taken (DisBRI) and unnecessary radiation exposure in irrelevant regions (UREIR) during radiography. We compared the rates of URE between very low-birth-weight (VLBW, birth weight < 1500 g) infants and non-VLBW infants. A total of 306 radiographs from 88 infants were taken. The means ± standard deviations (SDs) of gestational age and birth weight were 35.7 ± 3.6 weeks and 2471 ± 816 g, respectively. Each infant underwent an average of 3.5 radiographs. The DisBRI rate was 1.3% and was mostly related to poor adherence to requests. The UREIR rates in thoraco-abdominal babygrams were 89.6% for the head, 14.8% for the elbows and 18.4% for the knee and were mainly related to improper positioning of and collimation in infants while performing radiography. The UREIR rates for the head, knee and ankle were higher in VLBW infants than in non-VLBW infants (94.6% vs. 85.6%, 27.0% vs. 11.5% and 5.4% vs. 0.7%, respectively, p < 0.05). CONCLUSIONS: URE during diagnostic radiography is common in sick infants and is mainly related to improper positioning and collimation during examinations. Adherence to protocols when performing radiographic examination or using ultrasonography may be a solution to reduce URE in infants in NICUs. WHAT IS KNOWN: • The risk of unnecessary radiation exposure (URE) during radiography has been a common and important issue in sick infants in neonatal intensive care units (NICUs). • The new point-of-care ultrasound (POCUS) technique decreases the need for chest films and prevents radiation exposure in neonates. WHAT IS NEW: • In the NICU, URE is still a common issue in critically ill infants during radiographic examinations. The causes of URE during diagnostic radiography are mainly due to improper positioning and collimation during examinations. • The incidence of URE in irrelevant regions is higher in very low-birth-weight (VLBW) infants than in non-VLBW infants.

The joint effect of gestational diabetes mellitus and hypertension contribute to higher risk of diabetes mellitus after delivery: a nationwide population-based study.

BACKGROUND: Gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) are known risk factors for postpartum diabetes mellitus (DM) and hypertension, respectively. This study aimed to examine the association between the co-occurrence of GDM and PIH and the subsequent development of diabetes mellitus (DM), hypertension, and metabolic syndrome. METHODS: A cohort study was conducted using data from the Taiwan National Health Insurance Research Database (TNHIRD). The study population included 2,297,613 pregnant women with no history of certain medical conditions who gave birth between 2004 and 2015. The women were classified into four cohorts based on their medical history: GDM cohort, PIH cohort, both GDM and PIH cohort, and normal cohort (without GDM and PIH). RESULTS: The GDM cohort had a higher risk of developing DM, hypertension, and metabolic syndrome than the normal cohort, with hazard ratios of 7.07, 1.54, and 2.51, respectively. The PIH cohort also had an increased risk for these conditions compared with the normal cohort, with hazard ratios of 3.41, 7.26, and 2.68, respectively. The cohort with both GDM and PIH had the highest risk of developing postpartum DM, hypertension, and metabolic syndrome, with hazard ratios of 21.47, 8.02, and 5.04, respectively, compared with the normal cohort. CONCLUSION: The cohort of patients with both GDM and PIH had the highest impact on developing postpartum DM compared with either condition alone cohort. Furthermore, the co-occurrence of both conditions increases the risk, with a higher likelihood of developing postpartum DM than hypertension or metabolic syndrome.

The novel roles of YULINK in the migration, proliferation and glycolysis of pulmonary arterial smooth muscle cells: implications for pulmonary arterial hypertension.

BACKGROUND: Abnormal remodeling of the pulmonary vasculature, characterized by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) along with dysregulated glycolysis, is a pathognomonic feature of pulmonary arterial hypertension (PAH). YULINK (MIOS, Entrez Gene: 54468), a newly identified gene, has been recently shown to possess pleiotropic physiologic functions. This study aims to determine novel roles of YULINK in the regulation of PAH-related pathogenesis, including PASMC migration, proliferation and glycolysis. RESULTS: Our results utilized two PAH-related cell models: PASMCs treated with platelet-derived growth factor (PDGF) and PASMCs harvested from monocrotaline (MCT)-induced PAH rats (PAH-PASMCs). YULINK modulation, either by knockdown or overexpression, was found to influence PASMC migration and proliferation in both models. Additionally, YULINK was implicated in glycolytic processes, impacting glucose uptake, glucose transporter 1 (GLUT1) expression, hexokinase II (HK-2) expression, and pyruvate production in PASMCs. Notably, YULINK and GLUT1 were observed to colocalize on PASMC membranes under PAH-related pathogenic conditions. Indeed, increased YULINK expression was also detected in the pulmonary artery of human PAH specimen. Furthermore, YULINK inhibition led to the suppression of platelet-derived growth factor receptor (PDGFR) and the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), and protein kinase B (AKT) in both cell models. These findings suggest that the effects of YULINK are potentially mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: Our findings indicate that YULINK appears to play a crucial role in the migration, proliferation, and glycolysis in PASMCs and therefore positioning it as a novel promising therapeutic target for PAH.

Execution of anticipatory guidance and the knowledge and practice gap among caregivers in Southern Taiwan: A retrospective study.

BACKGROUND/PURPOSE: This study examined the practice rate of Anticipatory Guidance (AG) and the gap between knowledge and practice among caregivers. METHODS: We retrospectively collected data from caregivers who brought their children for seven age-based well-child visits (birth to 7 years old) and seven corresponding AG checklists for practice (each ranged from 16 to 19 guidance items, 118 items in total) between 2015 and 2017. Practice rates of guidance items and their association with children's sex, age, residence, and body mass index were collected and analyzed. RESULTS: We enrolled 2310 caregivers (330 per well-child visit). Average practice rates of guidance items in the seven AG checklists were 77.6%-95.1%, generally without significant differences between urban/rural or male/female children. However, lower (<80%) rates were observed for 32 items, including dental check-ups (38.9%), use of fluoride toothpaste (44.6%), screen time (69.4%), and drinking less sugar-sweetened beverages (SSBs) (75.5%), with corresponding knowledge-to-practice gap rates of 55.5%, 47.9%, 30.3%, and 23.8%, respectively. "Drinking less SSBs" was the only item with a higher obesity rate in the non-achieved group versus the achieved group (16.7% vs. 7.4%, p = 0.036; odds ratio: 3.509, 95% CI: 1.153-10.677, p = 0.027). CONCLUSION: Caregivers in Taiwan practiced most AG recommendations. However, dental check-ups, fluoride toothpaste use, drinking less SSBs, and limiting screen time were less executed items. A higher obesity rate was found among 3-7-year-old children whose caregivers failed to practice the "Drink less SSBs" guidance. Strategies to overcome the gap between knowledge and practice are needed to improve these less-achieved guidance items.

Epicardial Adipose Tissue Was Highly Associated with Reduction in Left Ventricular Diastolic Function as Early as in Adolescence.

Background: Epicardial adipose tissue (EAT) is increased in adolescents with obesity and may play a role in early cardiovascular pathophysiological changes. There is a lack of evidence focusing on the association between EAT and cardiac function in adolescents. This study explored associations between EAT, left ventricle (LV) geometric, and LV functional changes in adolescents. Methods: Adolescent volunteers between 10 and 20 years of age were included. Body mass index (BMI) was presented as age- and sex-specific BMI z-scores. Blood samples for glucose metabolism, lipid profiles, and high-sensitivity C-reactive protein (hs-CRP) were obtained. EAT thickness, LV hypertrophy, and LV diastolic function were measured by echocardiography. Results: The mean age of the 276 adolescents was 13.51 ± 2.44 years. BMI z-score was strongly associated with EAT thickness (r = 0.77; p < 0.001). Multivariable analysis revealed that age, insulin resistance, total cholesterol to high-density lipoprotein cholesterol ratio, and hs-CRP were independent predictors of increased EAT thickness. After adjusting for sex, age, and BMI z-score by multivariable analysis, EAT thickness was a strong predictor of higher LV mass indexed to height2.7, higher relative wall thickness, lower mitral annulus e'/a', and higher E/e' of the mitral annulus. There was no association between EAT and LV ejection fraction. Conclusions: EAT was highly associated with LV hypertrophy and reduction in LV diastolic function, independent of BMI z-score in the enrolled adolescents. Of note, the negative impacts of EAT on LV geometry and diastolic function occurred as early as in adolescence. This highlights the importance of preventing obesity and EAT deposition early in life.

Age-dependent distribution of the atopic phenotype and allergen sensitization among asthmatic children in southern Taiwan.

BACKGROUND: Asthma is divided into atopic and non-atopic phenotypes. The percentages of atopic asthma and allergen sensitization in patients of different ages have not been well studied. OBJECTIVE: To determine the percentage distribution of atopic and non-atopic phenotypes in different age groups of asthmatic children, and investigate the distribution of specific IgE to different allergens when stratified by age group in southern Taiwan. METHOD: We conducted this hospital-based, retrospective, cross-sectional study in southern Taiwan between 2004 and 2006. Asthmatic children aged 3 to 18 years who were diagnosed according to the Global Initiative for Asthma guidelines were enrolled. The MAST-CLA system was used to detect 36 allergen-specific IgEs. RESULTS: A total of 620 asthmatic children were divided into three groups: preschool (3-6 years old, n=360), school-aged (7-12 years old, n=213), and adolescent (13-18 years old, n=41) children. The atopic and non-atopic phenotypes were observed in 54.8% and 45.2% of the asthmatic children, respectively. The atopic phenotype was observed in 45.6%, 65.7%, and 80.5% of the preschool, school-aged and adolescent groups, respectively. The percentages of the atopic phenotype were significantly different when stratified by age group (p<0.001), and there was a positive trend of percentage distribution. The percentages of sensitization to aeroallergens were significantly different and observed in 44.0%, 65.7%, and 80.5% of the preschool, school-aged and adolescent groups, respectively (p<0.001). There were positive trends between age groups and prevalence rates of sensitization to the main aeroallergen and other aeroallergen groups, but not to each allergen of the seafood or other food allergen group. CONCLUSIONS: A trend of an increasing percentage of the atopic phenotype when stratified by age group was found in asthmatic children in southern Taiwan. Aeroallergens contributed more to pediatric asthma than food allergens. The prevalence of sensitization to aeroallergens increased with increasing age when stratified by age group.

Hospital-based school for children with chronic illness in Taiwan.

BACKGROUND/PURPOSE: To provide educational support and avoid unwanted damage that may impede learning for children with chronic illness, the learning environment should be friendly and safe. There is a need to establish schools inside hospitals, however, which may be neglected in a highly efficient health care system. A study was conducted to identify hospital-based schools for sick children in Taiwan, and to explore the barriers for implementation. METHODS: The data were collected by structured telephone interview and retrieval of hospital web information. The study targeted social workers and nurses in the pediatric wards of 29 hospitals, plus officials from the Education Bureau in Taiwan. The interviewers inquired about the availability of a formal educational program inside hospitals and the barriers (if any) in providing educational supports. RESULTS: Taiwan has only one hospital-based informal school and eight hospitals with rotating bedside teachers. Education inside hospitals occurs mostly through voluntary teaching in informal education models. Information about special educational resources has not been widely distributed to patients and health care providers. Professional personnel in Taiwan are not well aware of the needs to establish a hospital-based school. CONCLUSION: The educational needs of children with chronic illness can be easily neglected even in an industrialized country. The establishment of policy and the enrichment of professional education on advocacy are necessary to eliminate educational inequities and benefit sick children.

Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca2+ Influx.

Up to 40% of patients with gastroesophageal reflux disease (GERD) suffer from proton pump inhibitor refractory GERD but clinically the medications to strengthen the lower esophageal sphincter (LES) to avoid irritating reflux are few in number. This study aimed to examine whether Salvia miltiorrhiza (SM) extracts induce tonic contraction of rat LES ex vivo and elucidate the underlying mechanisms. To investigate the mechanism underlying the SM extract-induced contractile effects, rats were pretreated with atropine (a muscarinic receptor antagonist), tetrodotoxin (a sodium channel blocker), nifedipine (a calcium channel blocker), and Ca(2+)-free Krebs-Henseleit solution with ethylene glycol tetraacetic acid (EGTA), followed by administration of cumulative dosages of SM extracts. SM extracts induced dose-related tonic contraction of the LES, which was unaffected by tetrodotoxin, atropine, or nifedipine. However, the SM extract-induced LES contraction was significantly inhibited by Ca(2+)-free Krebs-Henseleit solution with EGTA. Next, SM extracts significantly induce extracellular Ca(2+) entry into primary LES cells in addition to intracellular Ca(2+) release and in a dose-response manner. Confocal fluorescence microscopy showed that the SM extracts consistently induced significant extracellular Ca(2+) influx into primary LES cells in a time-dependent manner. In conclusion, SM extracts could induce tonic contraction of LES mainly through the extracellular Ca(2+) influx pathway.

Unmasking a hidden culprit: late-presenting congenital diaphragmatic hernia beyond infancy: A case report and literature review.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly with abnormal diaphragm development, typically diagnosed prenatally or soon after birth. Late-presenting CDH presents diagnostic challenges due to nonspecific symptoms that can lead to misdiagnoses. METHODS: This report discusses a 35-month-old female initially presenting with predominant gastrointestinal symptoms and minimal respiratory distress. Initial radiographic findings suggested a left tension pneumothorax, prompting further investigation. RESULTS: Subsequent diagnostic efforts revealed a Bochdalek-type left CDH, with several abdominal organs herniated into the thoracic cavity. The case was managed through laparotomy, where herniated contents were successfully repositioned into the abdominal cavity. This intervention underscores the need for high clinical suspicion and the importance of distinguishing between similar presentations, such as tension pneumothorax and tension gastrothorax, which require different management strategies. CONCLUSION: The case illustrates the importance of considering CDH in differential diagnoses for older pediatric patients with atypical symptoms. Early recognition and appropriate management are key to improving patient outcomes.

Changing patterns of infectious diseases in children during the COVID-19 pandemic.

Each infectious disease has had its own epidemic pattern and seasonality for decades. However, public health mitigation measures during the coronavirus disease 2019 (COVID-19) pandemic have resulted in changing epidemic patterns of infectious diseases. Stringent measures resulted in low incidences of various infectious diseases during the outbreak of COVID-19, including influenza, respiratory syncytial virus, pneumococcus, enterovirus, and parainfluenza. Owing to the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and subsequent immunity development, decreasing virulence of SARS-CoV-2, and worldwide immunization against SARS-CoV-2 in children beyond 6 months of age, mitigation measures are lifted country by country. Consequently, the immunity debt to infectious respiratory viruses other than SARS-CoV-2 contributed to the "off-season," "see-saw," and "upsurge" patterns of various infectious diseases in children. Moreover, apart from the persistence of SARS-CoV-2, the coexistence of other circulating viruses or bacterial outbreaks may lead to twindemics or tripledemics during the following years. Therefore, it is necessary to maintain hand hygiene and immunization policies against various pathogens to alleviate the ongoing impact of infectious diseases on children.

Posterior Sagittal Anorectoplasty for Acquired Imperforate Anus Complicated by Anorectal Necrosis: A Case Report.

Anorectal necrosis is an uncommon lethal disease in children, characterized by necrosis of the mucosa of the anus and rectum. The difference between anorectal necrosis and Fournier's gangrene is that anorectal necrosis does not affect the genital organs. The treatment for anorectal necrosis includes debridement of the anus, colostomy, and the use of broad-spectrum antibiotics. However, anorectal necrosis may lead to anal stricture, anal malfunction, or even acquired atresia of the anus. There is no consensus on the treatment for acquired imperforate anus. Herein, we report a case of a four-month-old boy with acquired imperforate anus complicated by anorectal necrosis. We describe our experience performing posterior sagittal anorectoplasty to reconstruct a neo-anus in such a rare case.

Chronic Nocturnal Abdominal Pain as the Presentation of Inverted Meckel Diverticulum: A Case Report.

The common clinical manifestations of Meckel's diverticulum include painless lower gastrointestinal bleeding and intestinal obstruction due to intussusception. Intussusception induced by inverted Meckel's diverticulum has rarely been reported; furthermore, there is no report thus far of chronic nocturnal abdominal pain as a presenting symptom in children with Meckel's diverticulum. A 4-year-and-10-month-old girl with no significant history of previous illness presented with the sole complaint of chronic nocturnal abdominal pain for 3 months. The patient was reported to be asymptomatic during the day. A provisional diagnosis of chronic ileoileal intussusception was already under consideration in her previous hospital visits elsewhere. Physical examination revealed a soft, non-distended abdomen without tenderness. Imaging studies revealed ileoileal intussusception. Exploratory laparotomy showed ileoileal intussusception induced by an inverted Meckel's diverticulum with ulceration. The patient underwent successful surgery and made a full recovery. We report this case to remind physicians that Meckel's diverticulum should be considered in differential diagnosis of children presenting with the isolated symptom of chronic nocturnal abdominal pain.

High Risk of Early Cataracts in Young Type 1 Diabetes Group: A Nationwide Cohort Study.

BACKGROUND: Chronic hyperglycemia in type 1 diabetes (T1D) patients results in ocular problems over time, but only a few studies emphasized on cataracts. AIM: To evaluate the epidemiology of cataracts in the T1D population. METHOD: A two-part study was conducted using data from the National Health Insurance Research Database in Taiwan. Information from the Longitudinal Health Insurance Database (LHID) was served as a template of the general population. In the first part, a total of 3,622 T1D cases registered between 1998 and 2007 were enrolled and compared with a matched group from the LHID. For identifying risk factors of cataracts in the T1D population in the second part, a total of 9032 T1D cases registered between 1998 and 2013 were included. RESULT: Compared to the LHID, the hazard ratio (HR) of cataracts in the T1D group was 5.81 (95% CI 4.60-7.33), and the HR was higher in females (6.29, 95% CI 4.63-8.55). The peak incidence of cataracts occurred between age 20 and 29 in the T1D group, while in the LHID, it was after 60. The overall incidence of cataracts in the T1D group was 9.1%. In T1D patients with cataracts, they were found with higher rates of associated diabetic complications. CONCLUSION: Compared to the nondiabetic population, cataracts seemed more rampant and premature in T1D patients, especially those of female gender. Early ophthalmologic examination should be considered in T1D patients.

High correlation between human rhinovirus type C and children with asthma exacerbations in Taiwan.

BACKGROUND/PURPOSES: Human rhinovirus type C (HRV-C) has been associated with asthma exacerbation (AE) in children in several countries. However, in Taiwan the association between HRV, especially HRV-C, and AE in children has yet to be elucidated. We sought to investigate the prevalence of respiratory viruses in children with acute lower respiratory tract infection (ALRTI) in Taiwan and the association between different types of HRV and AE in children. METHODS: This prospective study was conducted from 2011 to 2013, and enrolled children with ALRTI, including an asthma exacerbation group (AE; n = 28) and a Non-asthma group (n = 66). Viruses were detected by culture, reverse transcription-polymerase chain reaction, and molecular sequencing of nasopharyngeal swabs. RESULTS: The prevalence of identified respiratory viruses was 78.6% in the AE group and 65.2% in the Non-asthma group. The prevalence rates of HRV and HRV-C were significantly higher in the AE group than in the Non-asthma group (67.9% vs. 33.3% in HRV, p = 0.002; and 50% vs. 15.2% in HRV-C, p < 0.001). Among the children with HRV, the prevalence of HRV-C (68.4%) was higher than that of the other types of HRV (31.6%, including HRV-A 26.3%, and HRV-B 5.3%) in the AE group but not in the Non-asthma group (40.9% vs. 59.1%). CONCLUSIONS: HRV is the most predominant viral infection responsible for pediatric AE in Taiwan, and HRV-C is responsible for more of these exacerbations than HRV-A or HRV-B.

Serum apoptotic marker M30 is positively correlated with early diastolic dysfunction in adolescent obesity.

PURPOSE: Obesity in adolescence has been shown to be related to cardiac geometric and functional changes. Cardiac dysfunction in adults with obesity could be attributed to chronic low-grade inflammation, apoptosis of cardiomyocyte, and glucose metabolic disorder. The aforementioned association in adolescents with obesity have never been well studied. Our aim was to determine the types of cardiac dysfunction in adolescents with obesity and survey the association between cardiac dysfunction and chronic low-grade inflammation, apoptosis, and glucose dysregulation in adolescents with obesity. METHODS: Adolescents aged between 10 and 20 years were enrolled in this study. Body mass index, waist-to-hip ratio, blood pressure, glucose metabolism, and high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-α), and apoptosis marker M30 levels were measured. Echocardiographic indices were also measured. The association between serum biomarkers and echocardiographic function parameters was analyzed. RESULTS: Diastolic dysfunction was the major finding in the cardiac functional assessment. The main changes in glucose metabolism were elevated C-peptide level and insulin resistance. Hs-CRP, IL-6, and M30 levels also increased with adolescent obesity. M30 was the major biomarker that was highly correlated to diastolic dysfunction indices in adolescents with obesity. CONCLUSIONS: Diastolic dysfunction was the main change in adolescent obesity. Insulin resistance, apoptotic marker M30, hs-CRP, and IL-6 were all elevated in adolescents with obesity. Only M30 was related to indices of left ventricular diastolic dysfunction among adolescents with obesity, rather than inflammation or insulin resistance.

Phthalate exposure alters gut microbiota composition and IgM vaccine response in human newborns.

Postnatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, is associated with allergy development in childhood, suggesting that DEHP exposure may dysregulate immune response in infants. We investigated whether DEHP exposure in newborns through medical treatment affected the gut microbiota pattern and vaccine response, which are both related to immune development. In this prospective cohort study from May 1, 2016 through July 31, 2017, newborns with respiratory distress who were given intravenous infusions (IVs) were enrolled as the DEHP group, and newborns who did not receive IVs were enrolled as the control group. We excluded patients with perinatal maternal probiotics, vaginal delivery, antibiotic treatment, and exclusive human milk or formula feeding. Of 118 infants, urinary phthalate metabolite analysis revealed that the calculated DEHP concentrations of the newborns treated with IVs (n = 15) were higher than those in the control group (n = 10) (p = 0.0001). DEHP exposure altered bacterial communities both in composition and diversity, particularly decreases in Rothia sp. and Bifidobacterium longum in the DEHP group. Furthermore, DEHP exposure significantly enhanced anti-HBsAg-IgM responses in the DEHP group (p = 0.013). Early-life DEHP exposure alter gut microbiota of newborns and may change their immune responses in later life.

L-Arginine and L-Citrulline Supplementation Have Different Programming Effect on Regulatory T-Cells Function of Infantile Rats.

Arginine is a semiessential amino acid in healthy adult human, but is essential for preterm, newborn or critically ill patients. Arginine can be supplied from our diet or de novo synthesis from citrulline. In conditions of sepsis or endotoxemia, arginine may be deficient and be accompanied with altered immune response. L-arginine supplementation can ameliorate dysregulated immune condition and improve prognosis. Many studies had tried L-arginine or L-citrulline supplementation to examine the effect on immune response in the adult population. Few had studied on the young children. In this study, we determined the effect of L-arginine and L-citrulline supplementation on the immune response of infantile rats. Male infantile rats received normal saline, L-arginine (200 mg/kg/day) or L-citrulline (200 mg/kg/day) intraperitoneally over postnatal day 8 to day 14. The infantile rats were then sacrificed. The blood was analyzed while the spleen was indicated for immune analysis after stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS). We found L-arginine supplementation enhanced Th1 immune response by increasing IFN-γ production. Both the L-arginine and L-citrulline therapy can modulate regulatory T-cell (Treg) immune effects by increasing the IL-10 level. Only the L-citrulline group showed a TGF-ß1 increase. Both L-arginine and L-citrulline therapy were also noted to decrease SMAD7 expression and enhance SIRT-1 abundance. However, FOXP3 expression was only modulated by L-citrulline treatment. We then concluded that L-arginine and L-citrulline supplementation can modulate the regulatory T-cells function differently for infantile rats.

Mechanism of resveratrol-induced relaxation of the guinea pig fundus.

BACKGROUND: Resveratrol is a polyphenolic compound that can be isolated from plants and also is a constituent of red wine. Resveratrol induces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. PURPOSE: Impaired gastric accommodation plays an important role in functional dyspepsia and fundic relaxation and is a therapeutic target of functional dyspepsia. Although drugs for fundic relaxation have been developed, these types of drugs are still rare. The purpose of this study was to investigate the relaxant effects of resveratrol in the guinea pig fundus. STUDY DESIGN: We studied the relaxant effects of resveratrol in the guinea pig fundus. In addition, we investigated the mechanism of resveratrol-induced relaxation on the guinea pig fundus by using tetraethylammonium (a non-selective potassium channel blocker), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channels), glibenclamide (an ATP-sensitive potassium channel blocker), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na+ channel blocker), ω-conotoxin GVIA (a selective neuronal Ca2+ channel blocker) and G-15 (a G-protein coupled estrogen receptor antagonist). RESULTS: The results of this study showed that resveratrol has potent and dose-dependent relaxant effects on the guinea pig fundic muscle. In addition, the results showed that resveratrol-induced relaxation of the guinea pig fundus occurs through nitric oxide and ATP-sensitive potassium channels. CONCLUSION: This study provides the first evidence concerning the relaxant effects of resveratrol in the guinea pig fundic muscle strips. Furthermore, resveratrol may be a potential drug to relieve gastrointestinal dyspepsia.