A comprehensive review of the applications of RNA sequencing in celiac disease research.

RNA sequencing (RNA-seq) has undergone substantial advancements in recent decades and has emerged as a vital technique for profiling the transcriptome. The transition from bulk sequencing to single-cell and spatial approaches has facilitated the achievement of higher precision at cell resolution. It provides valuable biological knowledge about individual immune cells and aids in the discovery of the molecular mechanisms that contribute to the development of autoimmune diseases. Celiac disease (CeD) is an autoimmune disorder characterized by a strong immune response to gluten consumption. RNA-seq has led to significantly advanced research in multiple fields, particularly in CeD research. It has been instrumental in studies involving comparative transcriptomics, nutritional genomics and wheat research, cancer research in the context of CeD, genetic and noncoding RNA-mediated epigenetic insights, disease monitoring and biomarker discovery, regulation of mitochondrial functions, therapeutic target identification and drug mechanism of action, dietary factors, immune cell profiling and the immune landscape. This review offers a comprehensive examination of recent RNA-seq technology research in the field of CeD, highlighting future challenges and opportunities for its application.

Compliance and Lifestyle of Children with Celiac Disease in the Iranian Children.

Background: Celiac disease is popular and needs a proper and constant gluten-free diet. However, data on the experience of the disease by children are insufficient. A few children have difficulty adjusting their lifestyles, and gluten-free foods are difficult for them. The present study aimed to find influential factors in the growth disorders and nonresponse to the treatment diet in celiac patients. Materials and Methods: We gave a list of all children with celiac disease to the project manager and according to the criteria extracted additional information from their files. Duodenal biopsies on 382 patients with suspected celiac disease and 93 patients with positive pathology were included in the study, regardless of antibody and genetic titer, then analyzed their information using appropriate statistical tests. Results: The mean age of individuals was 9.48 ± 3.88, and 35 were male and 58 female. At the age of <5, there was more growth disorder than other age groups. The recovery percentage in short stature was significantly better in children with higher marches, and they responded better to the treatment regimen. Individuals with comorbidities had higher anti-tTG and lower Hb levels, higher incidence of growth disorder, did not respond to the treatment regimen. Those with a first-degree relative with celiac disease had a lower growth disorder than others. Conclusion: Identifying and correcting nutritional disorders in patients with celiac disease need to evaluate persistent symptoms and identify their causes to plan appropriate treatment and follow-up of patients with celiac disease step by step and continuously.

Health care providers' communication with pediatric patients and carers: a best practice implementation project.

INTRODUCTION AND OBJECTIVES: Health care providers need a high level of communication skills in dealing with pediatric patients and their carers. The objective of this project was to evaluate current practice and implement best practices promoting health care provider communication with pediatric patients and carers in a children's hospital in Tabriz, Iran. METHODS: This project used the JBI Model of Evidence-Based Healthcare, which guided the conceptualization of evidence implementation, context analysis, project implementation, and evaluation of outcomes using evidence-based quality indicators. An audit and feedback strategy was adopted to measure baseline compliance with best practices, develop strategies to address areas of non-compliance, and conduct a final audit to measure any changes in compliance. Four criteria were developed for the baseline and follow-up audits. Criteria 1 and 2 were evaluated using a sample of 30 health care providers, while Criteria 3 and 4 were evaluated using a sample of 80 pediatric patients and carers. RESULTS: All four criteria improved at the end of the project. Criterion 1 (health care staff receive communication skills training) had the highest mean score at baseline and follow-up (63% and 83%, respectively). Criterion 2 (implementation of local strategies by health care organizations) increased from 45% to 55%. However, this rate of improvement was the lowest of all the criteria. Criterion 3 (pediatric patients receive relevant education) improved from low to moderate, rising from 18% to 49%. A more significant improvement was noted for Criterion 4 (parents receive relevant education), which rose from 19% to 56%. CONCLUSIONS: The strategies implemented in this project successfully improved health care provider communication with pediatric patients and their carers. To ensure project sustainability, repeat audits will be conducted after 3, 6, and 12 months. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A199.

High-fat diet-induced biogenesis of pulmonary exosomes in an experimental rat model.

BACKGROUND: High-fat diets (HFD) have recently become a public health concern. We hypothesize that HFD induces exosomes biogenesis in the lung tissue of rat model. METHODS AND RESULTS: Sixteen adult male Wistar rats were fed with HFD or a regular chow diet for 3 months. The histopathological changes in lung tissues were measured by hematoxylin and eosin (H&E) staining. Bronchoalveolar lavage (BAL) was performed to assay exosomes by acetylcholinesterase enzyme (AhCE) activity. Real-time PCR (qPCR) was used to evaluate Rab27-b, Alix, and IL-1ß expression, while the immunohistochemical examination was performed for CD81 expression in lung tissues. In addition, expression of IL-1ß was detected by ELISA. We found pathological alterations in the lung tissue of HFD animals. AhCE activity along with the expression level of Rab27-b, Alix, and IL-1ß was increased in HFD animals (p < 0.05). Immunohistochemical staining showed that expression of CD81 was increased in lung tissues of HFD animals compared with the control group (p < 0.05). CONCLUSION: Hence, HFD induced exosomes biogenesis and histopathological changes with IL-1ß expression in rats' lung tissues.

Therapeutic application of mesenchymal stem cells derived exosomes in neurodegenerative diseases: A focus on non-coding RNAs cargo, drug delivery potential, perspective.

Despite the massive efforts advanced over recent years in emerging therapies for neurodegenerative diseases, effective treatment for these diseases is still an urgent need. The application of mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) as a novel therapy for neurodegenerative diseases holds great promise. A growing body of data now suggests that an innovative cell-free therapy, MSCs-Exo, may establish a fascinating alternative therapy due to their unique advantages over MSCs. Notable, MSCs-Exo can infiltrate the blood-brain barrier and then well distribute non-coding RNAs into injured tissues. Research shows that non-coding RNAs of MSCs-Exo are vital effectors that participate in the treatment of neurodegenerative diseases through neurogeneration and neurite outgrowth, modulation of the immune system, reducing neuroinflammation, repairmen of damaged tissue, and promotion of neuroangiogenesis. In addition, MSCs-Exo can serve as a drug delivery system for delivering non-coding RNAs to neurons in neurodegenerative conditions. In this review, we summarize the recent progress in the therapeutic role of non-coding RNAs of MSCs-Exo for various neurodegenerative diseases. This study also discusses the potential drug delivery role of MSCs-Exo and challenges and opportunities in the clinical translation of MSCs-Exo-based therapies for neurodegenerative diseases in the future.

Harnessing Normal and Engineered Mesenchymal Stem Cells Derived Exosomes for Cancer Therapy: Opportunity and Challenges.

There remains a vital necessity for new therapeutic approaches to combat metastatic cancers, which cause globally over 8 million deaths per year. Mesenchymal stem cells (MSCs) display aptitude as new therapeutic choices for cancer treatment. Exosomes, the most important mediator of MSCs, regulate tumor progression. The potential of harnessing exosomes from MSCs (MSCs-Exo) in cancer therapy is now being documented. MSCs-Exo can promote tumor progression by affecting tumor growth, metastasis, immunity, angiogenesis, and drug resistance. However, contradictory evidence has suggested that MSCs-Exo suppress tumors through several mechanisms. Therefore, the exact association between MSCs-Exo and tumors remains controversial. Accordingly, the applications of MSCs-Exo as novel drug delivery systems and standalone therapeutics are being extensively explored. In addition, engineering MSCs-Exo for targeting tumor cells has opened a new avenue for improving the efficiency of antitumor therapy. However, effective implementation in the clinical trials will need the establishment of standards for MSCs-Exo isolation and characterization as well as loading and engineering methods. The studies outlined in this review highlight the pivotal roles of MSCs-Exo in tumor progression and the promising potential of MSCs-Exo as therapeutic drug delivery vehicles for cancer treatment.

Engineered Exosomes for Tumor-Targeted Drug Delivery: A Focus on Genetic and Chemical Functionalization.

Cancer is the main cause of death worldwide. The limitations in traditional cancer therapies provoked the advance and use of several nanotechnologies for more effective and nontoxic cancer treatment. Along with synthetic nanocarriers, extracellular vesicles (EVs)-mediated drug delivery systems have aroused substantial interest. The term EVs refers to cell-derived nanovesicles, such as exosomes, with phospholipid-bound structures, participating in cell-to-cell communication. Exosomes are 30-150 nm vesicles that can transfer many biological molecules between cells. From a drug delivery standpoint, exosomes can be loaded with various therapeutic cargo, with the several advantages of low immunogenicity, high biocompatibility, transformative, and effective tumor targeting aptitude. The exosomal surface can be functionalized to improve tumor targeting ability of them. Researchers have genetically expressed or chemically linked various molecules on the surface of exosomes. Despite extensive investigation, clinical translation of exosome-based drug delivery remains challenging. In this review, we discuss various methods used to loading exosomes with therapeutic cargo. We describe examples of functionalized exosomes surface using genetic and chemical modification methods. Finally, this review attempts to provide future outlooks for exosome-based targeted drug delivery.

A review and experimental study on the application of classifiers and evolutionary algorithms in EEG-based brain-machine interface systems.

OBJECTIVE: Considering the importance and the near-future development of noninvasive brain-machine interface (BMI) systems, this paper presents a comprehensive theoretical-experimental survey on the classification and evolutionary methods for BMI-based systems in which EEG signals are used. APPROACH: The paper is divided into two main parts. In the first part, a wide range of different types of the base and combinatorial classifiers including boosting and bagging classifiers and evolutionary algorithms are reviewed and investigated. In the second part, these classifiers and evolutionary algorithms are assessed and compared based on two types of relatively widely used BMI systems, sensory motor rhythm-BMI and event-related potentials-BMI. Moreover, in the second part, some of the improved evolutionary algorithms as well as bi-objective algorithms are experimentally assessed and compared. MAIN RESULTS: In this study two databases are used, and cross-validation accuracy (CVA) and stability to data volume (SDV) are considered as the evaluation criteria for the classifiers. According to the experimental results on both databases, regarding the base classifiers, linear discriminant analysis and support vector machines with respect to CVA evaluation metric, and naive Bayes with respect to SDV demonstrated the best performances. Among the combinatorial classifiers, four classifiers, Bagg-DT (bagging decision tree), LogitBoost, and GentleBoost with respect to CVA, and Bagging-LR (bagging logistic regression) and AdaBoost (adaptive boosting) with respect to SDV had the best performances. Finally, regarding the evolutionary algorithms, single-objective invasive weed optimization (IWO) and bi-objective nondominated sorting IWO algorithms demonstrated the best performances. SIGNIFICANCE: We present a general survey on the base and the combinatorial classification methods for EEG signals (sensory motor rhythm and event-related potentials) as well as their optimization methods through the evolutionary algorithms. In addition, experimental and statistical significance tests are carried out to study the applicability and effectiveness of the reviewed methods.

Comparison of Ciprofloxacin-Based Triple Therapy with Conventional Triple Regimen for Helicobacter pylori Eradication in Children.

Helicobacter pylori infection is a prevalent disease among Iranian children. The purpose of this study was to compare the effect of ciprofloxacin and furazolidone on eradicating helicobacter pylori in Iranian children in combination with amoxicillin and omeprazole. In this cohort study, helicobacter pylori infection was confirmed by gastroscopy, rapid urease test or pathologic assessments. A total of 66 children were randomly enrolled; based on the random number table, and were divided into two groups; first, a combination regimen consisting of ciprofloxacin, amoxicillin, and omeprazole; second, a three-medication regimen consisting of amoxicillin, furazolidone, and omeprazole. The effect of both medical regimens on the successful eradication of helicobacter pylori infection was assessed and compared. Chi-square test was used for evaluating the association between quantitative variables. All comparisons were made at the significance of P<0.05. Endoscopic tests prior to initiating treatments showed that 66.7% of the patients had a degree of nodularity while peptic ulcer was only observed in one patient. One month after the end of the treatments, eradication of the helicobacter pylori infection was reported 87.9% (29/33) in the first group (CAO) and 60.6% (20.33) in the second group (FAO) (P=0.011). It appears that a major advantage of our proposed regimen over others is a lack of wide use of fluoroquinolones for treating children's diseases. Given FDA's recommendation about the possibility of prescribing ciprofloxacin for infected patients with multidrug resistance, we can use the regimen proposed in this study in patients with resistance to standard treatments.

Topical tranexamic acid as a novel treatment for bleeding peptic ulcer: A randomised controlled trial.

BACKGROUND: Peptic ulcers are among the most common causes of upper gastrointestinal (GI) bleeding in children. The standard care for GI bleeding is endoscopy for diagnostic and therapeutic purposes. We aimed to assess the effect of topical tranexamic acid (TXA) via endoscopic procedures in children with GI bleeding caused by bleeding ulcers. PROCEDURE: In this randomised controlled trial, 120 children were evaluated by diagnostic procedures for GI bleeding, of which 63 (30 girls, 33 boys) aged 1-month to 15 years were recruited. The patients were randomly divided into case and control groups. In the case group, TXA was administered directly under endoscopic therapy. In the control group, epinephrine (1/10,000) was submucosally injected to the four quadrants of ulcer margins as the routine endoscopic therapy. In both groups, the patients received supportive medical therapy with intravenous fluids and proton pump inhibitor drugs. RESULTS: The mean ± standard deviation age of the children was 5 ± 2.03 years. Rebleeding occurred in 15 (11.4%) and 21 (9.8%) patients in the case and control groups, respectively (P = 0.50). The frequency of blood transfusion episodes (P = 0.06) and duration of hospital stay (P = 0.07) were not statistically different between the groups. CONCLUSION: Using topical TXA via endoscopic procedures may be effective in cases of GI bleedings caused by active bleeding ulcers. In order to establish this therapeutic effect, a large number of clinical studies are needed.

Granulomatous hepatitis as a rare complication of Bacillus Calmette-Guérin vaccination.

Bacillus Calmette-Guérin (BCG) vaccine, which is a widely practiced vaccine in some regions, could lead to a variety of complications. Herein, a 2-month-old infant is presented who was referred because of hepatosplenomegaly and diarrhea. Liver biopsy indicated multiple small and large granulomas composed of epithelioid histiocytes; granulomas resided in portal or lobular areas. The diagnosis of granulomatous hepatitis was made, and treatment with isoniazid, rifampine, and ethambutol were started. Liver function tests were normalized and hepatosplenomegaly was reduced in an 8-month follow-up. The presence of epithelioid cell granuloma in the liver may indicate a diagnosis of disseminated BCG as a rare complication of vaccination. Prompt diagnosis and appropriate treatment could prevent further complications in the affected patients.

Diagnostic endoscopy and clinical characteristics of gastrointestinal bleeding in children: a 10-year retrospective study.

BACKGROUND: Upper gastrointestinal (UGI) endoscopy is a tool used frequently in the evaluation of patients presented with hematemesis. OBJECTIVES: The purpose of this study was to evaluate clinical presentations and features of UGI bleeding (UGIB) in children. METHODS/PATIENTS AND MATERIALS: A descriptive retrospective analysis was carried out on the medical records of the patients. Children and adolescents aging 0 - 18 years who were presented with UGIB were recruited in the survey over a period of 10 years (2000 to 2010) in Children's Hospital, Tabriz, Iran. RESULTS: There were 447 patients included in this study and they were all evaluated by upper endoscopy. Clinical manifestations included hematemesis (120 cases, 26.85%), melena (60 cases, 13.42%), and hematochezia (11 cases, 2.46%). Age-related analysis showed that erosive esophagities was a more common cause of hematemesis in the younger age group (under 1 year of age) with a prevalence of 37% when compared with elder children and adolescents (40%). Peptic ulcer disease was seen in only 7.4% of infants under the age of one. Overall, Esophagitis and erosive esophagitis was the most common endoscopic finding (179, 40%) . CONCLUSIONS: There were 80 (17.90%) patients receiving endoscopic hemostatic therapy. In children with UGIB, upper endoscopy is a diagnostic procedure for the categorization of underlying causes of upper gastrointestinal bleeding in children and various endoscopic lesions may be found in a patient with the impression of UGIB.

Immunoproliferative small intestinal disease presented with ascites and edema.

Immunoproliferative small intestinal disease (IPSID) is a rare disorder, which can progress to malignancy and invasion. Herein, a male patient is presented with hypoalbuminemic ascites and a history of chronic diarrhea five years before. Small intestinal biopsy and immunohistochemical study suggested the diagnosis of IPSID; the patient was then successfully treated with antibiotics. Considering the favorable therapeutic response of IPSID to antibiotics during primary stages, clinicians should be aware of its various presentations in order to initiate treatment at an early

Joubert syndrome presenting as unilateral dysplastic kidney, hypotonia, and respiratory problem.

An 8-month-old girl with a history of asphyxia and respiratory distress immediately after birth was hospitalized at her fourth month of age with the diagnosis of kidney infection and it was revealed that she had a unilateral multicystic dysplastic kidney. In recent admission, she presented to emergency room with fever, hyperpnea, and apnea. In appearance, she was a hypotonic girl with broad forehead, hypertelorism, depressed nasal bridge and bitemporal regions, rapid vertical and horizontal nystagmus, and open mouth with salivation. In spite of normal physical growth, she had delayed developmental milestones. Blood gas O 2 saturation dropped after she received phenobarbital. Her urinary and blood tests were normal; however, her cranial magnetic resonance imaging (MRI) revealed vermis agenesis and molar tooth sign. These physical and para-clinical findings suggested Joubert syndrome.

Insomnia and limb pain in hemodialysis patients: what is the share of restless leg syndrome?

Insomnia and limb pain are common problems in dialysis patients. In addition, restless leg syndrome (RLS) as a specific cause of insomnia and limb pain has been reported in many studies. The purpose of this study was to estimate incidence of insomnia and RLS as a cause of insomnia in these patients. Twenty-six patients undergoing hemodialysis were investigated for insomnia, limb pain and RLS as per the defined criteria. They were evaluated for dialysis quality, dialysis duration, hemoglobin, serum phosphorous, ionized calcium, iron and ferritin levels. These variables between patients with insomnia and those with normal sleep were evaluated by independent "t" test. Without considering the etiology or pathogenesis of insomnia, we evaluated the occurrence of insomnia and limb pain in these patients, and specifically, restless leg syndrome. Insomnia and limb pain were common in dialytic patients. 46% of patients had insomnia. 91% of sleepless group had limb pain as a persistent, annoying complaint. Limb pain was not seen in groups with a normal sleep pattern. Restless leg syndrome was found in 8% of total cases (2 out of 26) and 17% among the insomnia group (2 out of 12). In spite of high incidence of insomnia among patients undergoing regular hemodialysis, role of RLS is trivial. There is a strong relationship between hemoglobin levels and duration of renal replacement therapy to insomnia occurrence.

Kidney imaging in management of delayed febrile urinary tract infection.

We report a cross-sectional study performed to evaluate the imaging findings of 40 children, aged one month to five years (16.65 ± 14.97 months), who presented with protracted fever of more than 48 hours due to urinary tract infection (UTI). About 85% of the patients had positive Tc99-Dimercaptosuccinic acid (DMSA) scan and 58% had vesicoureteral reflux (VUR). Kidney sonography aided in the diagnosis and treatment in 10% of the patients. Age, sex, presence or laterality of VUR did not contribute to defective DMSA scan (pyelonephritis) (P > 0.05). Delayed diagnosis and treatment of febrile UTI is associated with a high incidence of positive findings of DMSA scan irrespective of age, sex or presence/absence of VUR. In mild VUR, the DMSA scan may be normal while in patients with moderate and severe VUR the DMSA scan is almost always abnormal. Thus, our study shows that a normal DMSA scan can help in ruling out moderate to severe forms of VUR and that cystography remains an excellent and standard tool for the diagnosis of VUR.

Beta thalassemia major: the effect of age on glomerular filtration rate.

Thalassemia is a common hereditary hemoglobinopathy disorder that affects many organs in the body. Estimation of kidney function is important, as it is the vital organ that plays the major role in the elimination of accumulated iron as well as the chelating drugs that have to be used as therapy. Sixty- three patients aged 1-29 years, with a mean ± SD of 14 ± 6.7 years, affected with beta- thalassemia major in Tabriz Children's Hospital were evaluated for their renal function on the basis of their age, serum iron, serum ferritin and serum creatinine levels along with two methods of estimating glomerular filtration rate (GFR); by Schwartz method for those under 18 years old and using Modification of Diet in Renal Disease (MDRD) formula for those who were 18 years and above. Elevation of serum creatinine denoting renal dysfunction was not seen in our patients, but hyperfiltration was a common finding. An increasing GFR was observed, which corresponded to age, but no relationships were seen between serum iron, serum ferritin, regular blood transfusion, chelating therapy to GFR.

Growth indices in urinary tract infection children with or without vesicoureteral reflux.

To determine the growth quality in children, less than 5 years of age, affected with urinary tract infection (UTI) and to compare the indices between patients with and without vesico-ureteral reflux (VUR) based on their reflux severity and/or laterality, we studied 106 children less than 5 years of age with UTI at Imam Reza Hospital of Kermanshah, Iran, and divided the study group into four subgroups based on their cystouretrography results as follows: Group 0: without reflux (as control group); Group 1: mild VUR; Group 2: moderate VUR; and Group 3: severe VUR. In all the subgroups, weight height index (WHI) was lower than 100% and was 96%, 93%, 95%, and 98%, respectively. We found no correlation between reflux severity and WHI in all the subgroups. In addition, the difference in the mean height standard deviation score (HSDS) (0.10, -0.12, -0.19, and -0.22, respectively) in the different subgroups was statistically insignificant. The mean WHI in the group with unilateral and bilateral reflux was 94.5% ± 8.9% and 95.0% ± 8.16%, respectively, while the mean HSDS was -0.16 ± 0.35 and -0.18 ± 0.38, respectively, and the difference was statistically insignificant in both the cases. We conclude that in children with UTI and normal glomerular filtration rate, the existence of reflux with all grades of severity and laterality exerts no impact on the growth index.