Overview of the compromised mucosal integrity in celiac disease.

Intestinal epithelium is a dynamic cellular layer that lines the small-bowel and makes a relatively impenetrable barrier to macromolecules. Intestinal epithelial cell polarity is crucial in coordinating signalling pathways within cells and mainly regulated by three conserved polarity protein complexes, the Crumbs (Crb) complex, partitioning defective (PAR) complex, and Scribble (Scrib) complex. Polarity proteins regulate the proper establishment of the intercellular junctional complexes including tight junctions (TJs), adherence junctions (AJs), and desmosomes which hold epithelial cells together and play a major role in maintaining intestinal barrier integrity. Impaired intestinal epithelial cell polarity and barrier integrity result in irreversible immune responses, the host- microbial imbalance and intestinal inflammatory disorders. Disassembling the epithelial tight junction and augmented paracellular permeability is a conspicuous hallmark of celiac disease (CD) pathogenesis. There are several dietary components that can improve intestinal integrity and function. The aim of this review article is to summarize current information about the association of polarity proteins and AJC damages with pathogenesis of CD.

Treatment of Patent Ductus Arteriosus in Premature Infants: Intravenous Paracetamol or Oral Ibuprofen?

BACKGROUND: The similarity in the mechanism of action between paracetamol and ibuprofen can cause similar side effects. However, in preterm neonates with feeding intolerance, intravenous (IV) paracetamol has replaced oral ibuprofen. Therefore, a comparison of the effectiveness and side effects is essential. METHODS: In this retrospective cohort study, the data of 118 preterm infants with a definite diagnosis of patent ductus arteriosus (PDA), including 59 patients who received oral ibuprofen and 59 patients who received IV paracetamol were analyzed. Laboratory evaluations of serum total and direct bilirubin, hemoglobin, and creatinine levels before and seven days after treatment were made. Using analysis of covariance (ANCOVA) and multiple multinomial logistic regression models, the effect of two treatment groups on the post-treatment variables as well as their efficacy comparison were evaluated. RESULTS: In both pre- and post-treatment periods, there was no significant association between echocardiography variables with treatment groups. The results from the ANCOVA model showed that the paracetamol and ibuprofen were followed by a significant decrease in the mean total bilirubin and Hct variables after treatment by 1.38 and 1.65 units, respectively. In addition, results from the Mann-Whitney U test revealed that the median Hb and K differences after and before treatment had a significant difference between the two treatment groups. Furthermore, based on the multiple multinomial logistic model results, the odds of complete arterial duct closure with IV paracetamol was 1.27 times higher than with oral ibuprofen, while in the oral ibuprofen group, the odds of closing was 1.44 times higher than the IV paracetamol group, but there was no statistically significant difference between the two groups. CONCLUSION: Intravenous paracetamol has equal efficacy compared to oral ibuprofen in the treatment of PDA. Also, it seems to be associated with a lower risk of hyperbilirubinemia following the treatment.

Comparison of Ocular and Brain Abnormalities Among Neonates With In Utero Exposure to Opium or Other Drugs.

Background There are growing concerns regarding ocular and brain abnormalities in infants who had in utero exposure to various kinds of substances/drugs. We compared the ocular and brain abnormalities among neonates based on the type of drug used by mothers. Methodology This prospective cohort study of 305 neonates included all neonates at Mahdieh Hospital, Tehran, Iran, who had their records for ophthalmic screening and brain sonography and were born to mothers with a history of substance use disorder (2014-2017). Demographic data, results for viral antibodies (human immunodeficiency virus, hepatitis C, and hepatitis B), and Apgar scores at one and five minutes were collected. We excluded neonates with Apgar score <8 at one minute, weight <1,800 g, gestational age <35 weeks, asphyxia, or anomalies. The neonates' eyes were examined using tropicamide 0.5%, phenylephrine 2.5%, and tetracaine. Results The prevalence of substance use disorder among pregnant women was 1.8%. The study included 305 neonates with a mean gestational age of 37.8 ± 1.6 weeks, while the mean age of their mothers with substance use disorder was 29.8 ± 6.4 years. Ophthalmologic examination showed that 37 (12%) neonates had abnormal incomplete retina vascularization, and brain abnormalities were seen in 29 (9.5%) neonates; however, no difference was identified based on the type of drug used by mothers. The birth weight (BW) of the neonates depended on the type of drugs used by the mothers (p = 0.027). Maternal use of cannabis and amphetamine were associated with the lowest and highest BWs (2,800 ± 283 and 3,750 ± 42 g), respectively. Conclusions The BW of neonates depended on the type of drugs used by the mothers, where cannabis and amphetamine use were associated with the lowest and highest BWs, respectively. However, our data could not identify if neonates' ocular and brain abnormalities differed based on the types of drugs. This study highlights the importance of a drug-free pregnancy and the need for addiction-prevention programs provided to women of childbearing age.

Possible Vertical Transmission From an Unsuspected SARS-CoV-2-Infected Mother to Her Newborn.

Although the Coronavirus Disease 2019 (COVID-19) has been found to have multiple routes of transmission, limited data exist on whether the vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can occur from asymptomatic infected mothers to their newborns during pregnancy. We report a full-term newborn girl who was found to be positive for COVID-19 at 24 hours of life and subsequently symptomatic with fever, tachycardia, tachypnea, elevated lactate dehydrogenase, and elevated total bilirubin. The newborn was delivered by a mother who was not suspected of having COVID-19 before giving birth, but who developed fever and dyspnea five hours after delivery and was found to be positive for COVID-19. Upon further history collection, the mother reported recent mild nasal congestion in the days prior to delivery. This case highlights that the vertical transmission of COVID-19 to a newborn may occur late during the third trimester from a mother who was not suspected of having the infection. All pregnant women may need to be screened for COVID-19 symptoms, including non-specific symptoms, prior to admission for labor and delivery floors in order to perform diagnostic tests and recommended safety precautions to keep newborns and hospital personnel safe.

Risk factors associated with serious bacterial infections among newborns with high body temperature.

INTRODUCTION: Recognizing the importance of serious bacterial infections (SBIs), study aimed to identify factors associated with high body temperature in newborns. METHODS: A convenience sample of 54 newborns admitted to our hospital in Iran (March-July 2015) with rectal temperature > 38°C (100.4°F) were examined for clinical signs, blood cultures, complete blood counts, platelets, Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), renal function, chest/abdominal x-rays, spinal tap, and history of maternal infections. RESULTS: Newborns had either fever due to infections, or hyperthermia due to dehydration and/or extreme warm environment. Bacterial infections (37%) included: sepsis (15%) (coagulase-positive or coagulase-negative Staphylococci, Enterobacter, Klebsiella, Escherichia coli), meningitis (13%), and 3.5% UTI, 3.5% pneumonia, 2% cellulitis, and 2% omphalitis. Degrees of dehydration experienced by 55.6% included 37% of cases associated with hyperthermia caused by warm clothing/environment, while in 18.6% dehydration was secondary to fever. Viral infections (11%) included upper respiratory infections, gastroenteritis, while in remaining 13% cause of high body temperature was unknown. The group with SBIs had higher chance of having history of PROM (premature rupture of membrane) (p = 0.023), positive CRP (p = 0.041), and abnormal platelets count (p = 0.021) comparing all others. CONCLUSIONS: High body temperature in newborns needs careful evaluation to identify fever due to SBIs. In sepsis cases, antibiotics should cover prevalent bacteria including Staphylococci and Enterobacter. Dehydration was prevalent among newborns with high body temperature due to hyperthermia or secondary to infections. To avoid hyperthermia, parents should know how to clothe their newborns appropriate for environmental temperature. Newborns' SBIs associated with positive CRP, abnormal platelet count, and maternal PROM.

The association between gut microbiota, cholesterol gallstones, and colorectal cancer.

Gut microbiota play critical roles in maintaining the human health in several aspects. Bile acids (BAs) are endogenous cholesterol-derived molecules that can be modified by the gut microbiota and act as signaling molecules in the regulation of host metabolic and physiology processes. Gut microbiota release many enzymes that are capable to perform considerable modifications on BAs such as bile salt hydrolases (BSH), 7α-dehydroxylase (CYP7A), and hydroxysteroid dehydrogenase (HSDH). These enzymatic roles can change in the gut microbiota composition, cause alteration in BAs profile and metabolism and even gallstone formation. Patients with 15 years of asymptomatic gallstone have increased risk for colorectal cancer (CRC), which may be related to altered gut microbiota, changes in bile metabolism, as well as cellular and molecular effects in the proximal colon. In gallstone-associated CRC patients, the association between consensus molecular subtypes of CRC should be clarified to identify if specific pathways are related.

Predication of hub target genes of differentially expressed microRNAs contributing to Helicobacter pylori infection in gastric non-cancerous tissue.

AIM: The main goal of this investigation was to provide an overview on H.pylori effect on gastric tissue via bioinformatics analysis of microarray-identified miRNAs and its target genes. BACKGROUND: MicroRNAs which control about 30 to 60% of gene expression in human body play a critical role in different cell growth stages. Expression modification of non-coding (NC) RNAs in H.pylori infections requires further investigations to provide better understanding of their roles in the body. METHODS: GSE54397, the microRNA microarray dataset, was analyzed by GEO2R, the online GEO database for detection of differentially expressed microRNAs and lastly the potential target genes as well as their associated pathways. RESULTS: A total of 244 miRNAs were detected as differentially expressed (p<0.05 and FC>2) in non-cancerous tissue of gastric with H.pylori infection in comparison with tissues without H.pylori infection. The findings indicated that hub microRNAs and target genes of up-regulated network are KIF9, DCTN3, and CA5BP1 along with hsa-miR-519d, hsa-miR-573, hsa-miR-646, hsa-miR-92a-1, hsa-miR-186, and hsa-miR-892a, respectively. For the down-regulated network, genes of RABGAP1, HSPB11 and microRNAs of hsa-miR-620, hsa-miR-19b-2, hsa-miR-555, and hsa-let-7f-2 were hubs. Most of the up-regulated microRNAs are involved in gastric cancer development while there is no evidence for the down-regulated ones. Yet, all of the hub down-regulated miRNAs are reported to have associations with different kinds of cancer. CONCLUSION: The introduced hub miRNAs and genes may serve as feasible markers in the mechanisms of H.pylori infection for different kinds of gastric diseases, in particular gastric cancer. However, their role requires further investigations.

Prevalence of vitamin D deficiency in pregnant mothers in Tehran and investigating its association with serum glucose and insulin.

PURPOSE: (1) To determine the prevalence of vitamin D deficiency in pregnant women. (2) To identify any correlations between maternal vitamin D levels and maternal and newborns' glucose and insulin levels. METHODS: This observational cohort study followed 149 healthy pregnant women visiting a hospital in Tehran, Iran in 2014 until the delivery of their term babies. Maternal serum vitamin D levels, and fasting blood glucose and insulin levels in both mothers and newborns were measured at delivery. Mothers' weight before pregnancy and right before delivery and babies' birth weight were measured. RESULTS: Of sample population, 27% had vitamin D deficiency, while 73% had insufficient vitamin D. No mother had sufficient vitamin D level. Maternal weight right before delivery negatively correlated with maternal serum vitamin D level (p = .04). Vitamin D deficiency is more prevalent in mothers who deliver a male infant (p = .03). Maternal serum vitamin D levels did not correlate with maternal or neonatal serum glucose or insulin levels or newborns' birth weight. Gestational age, maternal weight right before delivery, parity and maternal serum glucose predict infant's birth weight. CONCLUSION: Vitamin D deficiency/insufficiency is prevalent among pregnant women. Factors causing this epidemic need investigation. Promoting consumption of vitamin D-fortified foods and supplements among pregnant women is suggested.

Maternal zinc deficiency and congenital anomalies in newborns.

BACKGROUND: Zinc deficiency in pregnant women is common, especially in the third trimester of pregnancy. The available data, however, on the association between zinc deficiency and congenital malformations in the Iranian population are insufficient. The aim of this study was therefore to determine whether maternal serum zinc deficiency is associated with major congenital malformations in newborns. METHODS: This descriptive, case-control study involved mothers of 80 neonates with congenital anomalies (study group) admitted to the Mofid Children's Hospital, Tehran, Iran. During the same period (2014 and 2015), serum zinc was measured in 80 mothers who had delivered normal newborns without congenital malformations (control group). RESULTS: Mothers with serum zinc deficiency had a more than sevenfold risk of malformations in the fetus compared with mothers with normal serum zinc (OR, 7.013; 95%CI: 2.716-18.110). Newborns with malformation weighing ≤2500 g were associated with lower maternal serum zinc compared with the control group (P = 0.006). CONCLUSIONS: There is an association between congenital malformation in newborns and maternal zinc deficiency.

Associations between anthropometric characteristics and insulin markers in mothers and their neonates and with neonate`s birth weight: An observational cohort study.

Naseh A, Nourbakhsh S, Tohidi M, Sarkhail P, Najafian B, Azizi F. Associations between anthropometric characteristics and insulin markers in mothers and their neonates and with neonate`s birth weight: An observational cohort study. Turk J Pediatr 2017; 59: 625-635. This study aimed to identify possible associations between anthropometric characteristics and insulin markers of mothers and 1) their neonate`s birth weight, and 2) those markers of neonates. A prospective observational cohort of 100 healthy mothers who came to a hospital in Tehran in 2014 from pregnancy to delivery as well as their term neonates comprised the study population. Only newborns with weight within normal range were included. Anthropometric indices and serum glucose and insulin levels were measured in both mothers and neonates. Correlations between maternal body and serum indices and neonate`s serum indices and birth weight were assessed. Maternal weight before pregnancy (r= 0.3, p=0.001), at time of delivery (r= 0.3, p=0.001), and maternal body mass index (BMI) before pregnancy (r= 0.2, p=0.04) positively associated with neonate`s birth weight. For the neonates with normal birth weight, there was no correlation between maternal serum glucose and insulin levels and neonate`s serum glucose and insulin levels or birth weight. Neonate`s serum glucose correlated positively with insulin levels (r= 0.3, p=0.006) and HOMA-IR (r= 0.6, p < 0.0001); and negatively with HOMA-S (r= -0.6, p < 0.0001) and QUICKI (r= -0.5, p < 0.0001). Neonate`s insulin correlated positively with HOMA-IR (r= 0.9, p < 0.0001), and negatively with HOMA-S (r= -0.9, p < 0.0001), QUICKI (r= -0.9, p < 0.0001), gestational age (r= -0.2, p=0.03) and with glucose-insulin (GI) ratio (r= -0.9, p < 0.0001). Neonate`s GI ratio correlated positively with gestational age (r= 0.2, p=0.01). Maternal serum glucose and insulin showed positive correlation (r= 0.4, p < 0.0001). The lowest maternal insulin quartile had dominantly male and the highest quartile had dominantly female neonates (p=0.006). In conclusion, maternal anthropometric measures correlate with neonates` birth weight. Advancing health promotion to normalize these maternal parameters may reduce the incidence of abnormal birth weights among newborns.

Associations between maternal anthropometric characteristics and infant birth weight in Iranian population.

OBJECTIVE: To examine the (1) normal ranges of anthropometric and insulin resistance/sensitivity indices (homeostatic model assessment for insulin resistance, homeostatic model assessment for insulin sensitivity, and quantitative insulin sensitivity check index) for Iranian pregnant women and their newborns and (2) associations between maternal anthropometric and metabolic values and infants' birth weights among Iranian women. METHODS: Anthropometric and metabolic values of 163 singleton non-diabetic pregnant women in Tehran, Iran (2014) were collected before and during pregnancy and at delivery. Linear regression, multivariable regression, and Student t tests were used to evaluate correlations between birth weight and maternal variables. RESULTS: Linear regression modeling suggested that maternal serum glucose (p = 0.2777) and age (p = 0.6752) were not associated with birth weight. Meanwhile, maternal weight and body mass index before pregnancy (p = 0.0006 and 0.0204, respectively), weight at delivery (p = 0.0036), maternal height (p = 0.0118), and gestational age (p = 0.0016) were positively associated with birth weight, while serum insulin (p = 0.0300) and homeostatic model assessment for insulin resistance (p = 0.0334) were negatively associated with infant's birth weight. Using multivariate modeling, we identified severalconfounders: parity (multipara mothers delivered heavier babies compared to first-time mothers) explained as much as 24% of variation in birth weight (p = 0.005), maternal height explained 20.7% (p = 0.014), gestational age accounted for 19.7% (p = 0.027), and maternal body mass index explained 19.1% (p = 0.023) of the variation in the infant's birth weight. Maternal serum insulin and infant's sex were not observed to be associated with birth weight (p = 0.342 and 0.669, respectively) in the overall model. CONCLUSION: Overweight/obese women may experience higher incidence of delivering larger babies. Multivariable regression analyses showed that maternal body mass index and height, parity, and gestational age are associated with newborn's birth weight.

INSURE method (INtubation-SURfactant-Extubation) in early and late premature neonates with respiratory distress: factors affecting the outcome and survival rate.

We studied the effects of administering exogenous surfactant for the treatment of respiratory distress in premature neonates (born before 37 weeks of gestational age [GA]) and compared the role of different risk factors on the outcome as well as survival rate. All the neonates (242) suffered from moderate to severe respiratory distress, identified by clinical signs, chest X-ray, respiratory distress syndrome (RDS) score >6, and blood gas measurements. All the neonates included were treated by administering surfactant (Beractant or Poractant alfa, dosage 100 mg/kg). The INSURE method was "successful" in 74% of patients, meaning there was no need for a second dose of surfactant or mechanical ventilation repetition. The factors that determined the "success" (Table II) were as follows: type of delivery, weight, GA, and number of fetuses. The factors affecting survival were: number of fetuses, mechanical ventilation dependency, pregnancy complications, and type of surfactant. The INSURE method reduced mortality (91.3% survived).