Evaluation of Outcomes and Complications of Large Volume Paracentesis without Albumin and Coagulopathy Therapy in Pediatrics with Severe Ascites.

Background: Large-volume paracentesis has become the first treatment choice for patients with severe and refractory ascites. The studies have reported several complications after therapeutic paracentesis. But there are few published data on the complications with or without Albumin therapy. We aimed to analyze the safety and complications of large-volume paracentesis in children with or without albumin therapy. Methods: This study was conducted on children with severe ascites with chronic liver disease who underwent large-volume paracentesis. They were divided into albumin-infused and albumin non-infused groups. In the case of coagulopathy, no adjustment was made. Albumin was not administered after the procedure. The outcomes were monitored to evaluate the complications. To compare two groups, a t-test was utilized, and the ANOVA test was used to compare several groups. If the requirements for using these tests were not met, Mann-Whitney and Kruskal-Wallis tests were applied. Results: Decreased heart rate was observed in all time intervals and was meaningful six days after paracentesis. MAP also decreased statistically at 48 hours and six days after the procedure (P < 0.05). Other variables did not show any meaningful change. Conclusion: Children having tense ascites with thrombocytopenia, prolonged PT, Child-Pugh class C, and encephalopathy can undergo large-volume paracentesis without any complication. Albumin administration before the procedure in patients with low levels of Albumin (<2.9) can effectively overcome the problems of tachycardia and increased mean arterial pressure. There will be no need for Albumin administration after paracentesis.

Manifestation of leech infestation as severe gastrointestinal bleeding in a 3-year-old boy: a case report and review of the literature.

BACKGROUND: Leeches are a class of hermaphroditic parasites that can attach to various body parts and start sucking blood. Gastrointestinal (GI) bleeding due to leeches is a rare phenomenon that is more common in less developed countries. Common symptoms include melena, hematemesis, pallor, weakness, and fatigue. Due to the similar symptoms of this issue to the main differential diagnoses of GI bleeding in pediatrics, such as diarrhea, constipation, diverticulitis, esophagitis, and anal fissures, it is challenging to differentiate it from the rest. CASE PRESENTATION: We present a three-year-old boy who was transferred to our center with hematemesis, tarry stool, and a drop in hemoglobin level. He finally was diagnosed with a leech in his stomach. CONCLUSIONS: In less developed counties, the inability to reach safe drinking water, swim in lakes or springs, and inadequate awareness of public health information among individuals can be risk factors for leech infestation.

An evaluation of ascitic calprotectin for diagnosis of ascitic fluid infection in children with cirrhosis.

BACKGROUND: The most common infection in children with the hepatic disease with or without cirrhotic ascites is spontaneous bacterial peritonitis (SBP), which occurs in the absence of an evident intra-abdominal source of infection. The present study aims to assess the value of calprotectin in ascitic fluid in the diagnosis of ascitic fluid infection in children with liver cirrhosis. MATERIALS AND METHODS: In this cross-section study, 80 children with underlying liver disease who attended the Hepatology and Emergency Department in Shiraz University Hospitals were studied. All the patients were evaluated by a thorough history, clinical examination, laboratory investigations, diagnostic paracentesis with PMNLs count, and Calprotectin, which was measured in 1 mL ascitic fluid by ELISA. RESULTS: Thirty-five patients (43.75%) were diagnosed with ascitic fluid infection. Of these children 6 cases had positive ascitic fluid culture (SBP). Calprotectin was high in AFI patients with a statistically significant difference in AFI patients compared to non-AFI patients. The cut-off levels were 91.55 mg /L and the area under the curve was 0.971. So it can serve as a sensitive and specific diagnostic test for detection of AFI in children with underlying liver disease. CONCLUSION: Elevated ascitic calprotectin levels in cirrhotic patients are a diagnostic and reliable marker for the detection of AFI and are considered a surrogate marker for PMN.

Pediatric liver and kidney transplantation in the era of COVID-19: a follow-up study from a tertiary referral center in Iran.

BACKGROUND: We aimed to evaluate the impact of COVID-19 pandemic on pediatric transplant outcomes and determine whether to continue pediatric transplant activity or not, and how policies intended our center has been effective in preventing COVID-19 among organ transplant recipients. METHODS: We conducted a single-center, retrospective, cohort study of hospitalized pediatrics after organ transplantation at Shiraz transplant center since March to August 2020. All liver and kidney transplanted children were included the study and their laboratory and clinical related COVID-19 characteristics were followed up till 3 months after transplantation during hospitalization period and then weekly by the transplant committee. RESULTS: Fifty-one patients underwent transplantation including 11 kidney and 40 liver recipients. The mean age of the pediatric cases was 6.72 ± 5.47 years. A total of 11 patients died due to post-transplant complications, while none of the patients presented any sign or symptoms in favor of COVID-19 in the hospital course after transplantation. Six transplants including 2 kidney and 4 liver were canceled when positive PCR tests were detected in their donors before the surgery. In the 3 months of follow up, two patients presented with symptoms including high grade fever, malaise, rhinorrhea, and GI symptoms. Both patients had two negative PCR, and no radiologic or laboratory results regarding COVID-19 were also detected. One had positive influenza PCR, while the second one had a positive serologic test for EBV; CT, computed tomography CONCLUSION: Transplant programs could continue their activities during the COVID-19 pandemic with specific case selection, accurate screening methods and following protective protocols.

The effects of metformin administration on liver enzymes and body composition in non-diabetic patients with non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis: An up-to date systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. One treatment is the use of metformin but its efficacy remains to be established. OBJECTIVE: The present systematic review and meta-analysis aimed to provide a more robust examination of the evidence for the effectiveness of metformin for treating non-diabetic NAFLD patients. METHODS: An extensive literature search was undertaken using online databases (PubMed, Embase, Scopus, Web of Science and Cochrane Library) to detect randomized controlled trials (RCTs) investigating the effect of metformin administration on liver enzymes and body composition in non-diabetic NAFLD patients up to 10 December 2019. A random-effects or fixed-effect models were performed to pool weighted mean difference (WMD) and 95% confidence intervals (CI). RESULTS: Six RCTs involving 307 individuals were included to the present meta-analysis. Compared to controls, metformin significantly reduced body mass index (BMI) (WMD: -0.77 kg/m2, 95 % CI = [-1.46, -0.07], P = 0.03, I2 = 0.0 %) and serum aspartate aminotransferase (AST) (WMD: -5.94 U/L, 95 % CI = [-11.51, -0.38], P = 0.03, I2 = 67.6 %). Also, body weight (WMD: -2.70 kg, 95 % CI = [-5.49, 0.09], P = 0.05, I2 = 33.7%) was marginally significant and serum alanine transaminase (ALT) (WMD: -5.04 U/L, 95 % CI = [-13.92, 3.84], P = 0.26, I2 = 60.9 %) was not statistically significant affected by metformin administration. There was no evidence of publication bias. CONCLUSION: In summary, the present study emphasizes the clinical importance of metformin administration for improving liver function and body composition in non-diabetic NAFLD patients. Moreover, the further large-scale and well-designed RCTs are required to confirm these findings.

The effects of ginger supplementation on markers of inflammatory and oxidative stress: A systematic review and meta-analysis of clinical trials.

The present systematic review and meta-analysis was conducted to investigate the effects of ginger supplementation on markers of inflammatory and oxidative stress. PubMed, Embase, Scopus, and Web of Science were systematically searched to identify relevant clinical trials evaluating the effects of ginger on serum CRP (C-reactive protein), TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin-6), PGE2 (prostaglandin E2), TAC (total antioxidant capacity), and MDA (malondialdehyde) from inception up to September 2019. Mean difference and 95% confidence intervals were pooled using a random-effects model. Potential publication bias was assessed using visual inspection of funnel plot and Egger's weighted regression tests. After excluding irrelevant records, 20 full-text articles that included 25 separate studies were included to the meta-analysis. Pooled results of this study indicated a statistically significant effect of ginger on serum CRP, TNF-α, IL-6, TAC, and MDA levels following ginger supplementation in compared to the controls. Also, the effects of ginger on serum PGE2 was marginally significant. Moreover, the high heterogeneity was disappeared in subgroup analysis performed by age, duration, dosage, and quality. This current analysis indicates that ginger supplementation has a significant effects on serum inflammatory and oxidative stress markers.

Soft Palate Ulcer: An Unusual Presentation of a Posttransplant Lymphoproliferative Disorder.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. It has several clinical manifestations, including infectious mononucleosis-like syndrome, lymphadenopathy, and other organ involvement. Soft palate ulcer is a rare manifestation of PTLD. The aim of this study is to present a 17-year-old girl with liver transplantation due to metastatic liver disease. After transplantation, she presented with a painful whitish ulcerative lesion accompanied by central necrosis in the right soft palate area measuring about 3 cm×3.5 cm. Histopathologic evaluation of the lesion showed monomorphic B-cell-type PTLD. She received 6 courses of CHOP chemotherapy plus rituximab. In the follow-up, the lesion disappeared with scar formation. Therefore, PTLD has different clinical presentations and may involve any part of the body. Therefore, when an unusual oral lesion after solid organ transplantation is observed, PTLD should be considered in addition to other differential diagnoses.

Intestinal pseudo-obstruction as an unusual gastrointestinal presentation in pediatric human immunodeficiency virus infection.

Intestinal pseudo-obstruction is a condition in which the intestine's ability to push food through is reduced. It often leads to the dilation of the various parts of the bowel. It can be idiopathic or inherited from a parent, or caused by another disease. We report a rare case of human immunodeficiency virus (HIV) infection in a 3-year-old boy who referred with acute abdominal pain, and was later diagnosed as having intestinal pseudo-obstruction caused by HIV. The underlying causes of intestinal pseudo-obstruction should be taken into account. HIV induced pseudo-obstruction may be considered in the differential diagnosis of pediatric intestinal pseudo-obstruction in order to provide a timely diagnosis and optimal care of children with HIV.

A Comparison of the Effect of Kegel Exercises and Conventional Therapy versus Conventional Therapy Alone in the Treatment of Functional Constipation in Children: A Randomized Clinical Trial.

Background: There have been few studies on the effect of Kegel exercises on the treatment of functional constipation in children. Hence, the present study investigated the add-on role of Kegel exercises in children with functional constipation. Methods: This clinical trial was conducted on children with functional constipation, according to Rome IV, who were referred to the pediatric department of Imam Reza Clinic (Shiraz, Iran) in 2022. The sample consisted of 64 children who were randomly assigned to either the intervention or the control groups. In the control group, a pediatrician administered conventional therapy, including diet training, defecation training, and polyethylene glycol (PEG) syrup (0.7 g/Kg daily). In the treatment group, in addition to conventional therapy, a pediatrician taught Kegel exercises to the child both verbally and in writing in the presence of their parents. To investigate the effectiveness of the intervention, frequency of defecation, defecation time, assistance used for defecation, incomplete emptying, unsuccessful defecation, abdominal pain, and painful defecation were selected as the outcomes. Independent sample t test was used for continuous variables. Categorical variables were reported as frequency and percentages. To examine the difference in categorical outcome variables, Wilcoxon (pre and post), Chi square, and Fisher exact tests were used. Data were analyzed using SPSS software version 21. P<0.05 were considered statistically significant. Results: Twenty-seven (88.4%) patients in the Kegel exercise group reported a defecation time of less than 5 min, while only 12 (37.5%) patients in the control group reached this time, and this difference was statistically significant (P=0.001). Moreover, patients in the treatment group showed significant improvements in terms of incomplete emptying of stool, unsuccessful defecation, abdominal pain, and painless defecation (P=0.001, P=0.001, P=0.001, P=0.037, respectively). After intervention, the use of laxatives, digits, or enemas to assist defecation was not significantly different between the groups (P=0.659). Conclusion: Kegel exercise was an effective adjunctive treatment for pediatric functional constipation.Trial Registration Number: IRCT20230424057984N1.

Clinical Findings, Bacterial Agents, and Antibiotic Resistance in Children with Spontaneous Peritonitis in Southern Iran: An Academic Tertiary Referral Center's Experience.

Background: Spontaneous bacterial peritonitis (SBP) is a fatal complication of ascites fluid infection. The causes of SBP in children differ from those in adults, and these bacteria are frequently resistant to antibiotics. Therefore, this study investigated the clinical findings, bacterial etiology, and antimicrobial resistance in children with SBP. Methods: This study was conducted on all new pediatric ascites patients, who were admitted to the Department of Pediatric Gastroenterology, Namazi Hospital, affiliated with Shiraz University of Medical Sciences (Shiraz, Iran) from 2021 to 2022. Required data such as demographic information, and clinical information such as complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Gram staining, blood culture by Automated Blood Culture System (BACTEC), and antibiogram of ascites fluids by disc diffusion method were all collected. Finally, the data were statistically analyzed using SPSS Software (version 26). Besides, the t test, Fisher's exact, Mann-Whitney, and Chi square tests were used for data analysis. In all tests, P≤0.05 was considered statistically significant. Results: The present study examined 62 children with ascites of which 18 (29%) had SBP. The median (IQR) age was 2.5 (8.1) years. Thirty-four (54.8%) of the participants were girls. Abdominal pain was the most common clinical manifestation in patients (54%), and there was a significant association between abdominal pain and SBP (P=0.02). In 12 positive ascites fluid cultures, coagulase-negative staphylococci had the highest frequency (25%), followed by Escherichia coli (16.7%). Third-generation cephalosporins had a 25% sensitivity in the total positive cultures. This sensitivity was 33.3% for Gram-negative cultures and 16.6% for Gram-positive cultures. Conclusion: Although third-generation cephalosporins are recommended as the primary antibiotic for the empirical treatment of SBP, the present study found high bacterial resistance. Finally, empirical therapy should be tailored to each region's bacterial resistance features.

Diffuse hepatic calcifications in a transfusion-dependent patient with Beta-thalassemia: a case report.

Hepatic calcification is usually associated with infectious, vascular, or neoplastic processes in the liver. We report the first case of beta-thalassemia major with isolated diffuse hepatic calcification in a 23 year old woman, who had been transfusion-dependent since the age of 6 months. She was referred to our center with a chief complaint of abdominal pain. Computed tomography scan of the abdomen revealed diffuse hepatic calcification in the right, left, and caudate lobes of the liver. Her medical history disclosed hypoparathyroidism as well as chronic hepatitis C virus infection, which was successfully treated but led to early micronodular cirrhosis on liver biopsy. Other studies done to search for the cause of hepatic calcification failed to reveal any abnormalities. We suspect that hypoparathyroidism caused liver calcification, and should be, therefore, considered in the differential diagnosis of hepatic calcification if other causative factors have been ruled out.

Clinical characteristics of pediatric esophagitis in southern iran; a single-center experience.

BACKGROUND: We sought to determine the clinical characteristics of pediatric esophagitis in southern Iran. METHODS: This cross-sectional study was conducted over a 4-year period, from 2005 to 2009, in Nemazee Hospital, a tertiary healthcare center in Shiraz, southern Iran. We consecutively included all pediatric patients (<18 years) who underwent endoscopy in our center and had pathology-confirmed diagnosis of esophagitis. Data regarding the patients' demographic characteristics, comorbidities, and clinical findings were recorded using a questionnaire. All the patients underwent upper gastrointestinal endoscopy and biopsy of the esophagus, and the findings were recorded in the questionnaire. RESULTS: We studied 125 children, comprising 61 (48.8%) girls and 64 (51.2%) boys at a mean age of 6.6±5.5 years. Repeated vomiting was the prominent symptom in our series, with it being reported by 75 (60%) patients, followed by fever in 35 (28%). Erythema (33.6%), esophageal ulcer (11.2%), and whitish patch (8.0%) were the most common endoscopic findings, while reflux esophagitis (32.8%), chronic (6.4%) and acute esophagitis (5.6%), and candida esophagitis (5.6%) were the most common histological diagnoses. Only one (0.8%) patient was diagnosed as having eosinophilic esophagitis, aspergillosis, and graft-versus-host disease. CONCLUSION: Reflux was the most common cause of esophagitis in the pediatric population of southern Iran. Contrary to previous reports, the prevalence of eosinophilic esophagitis was far less than that estimated, while the prevalence of opportunistic infections was higher secondary to post-liver transplantation immunosuppression.

Identification of a novel mutation in the ALDOB gene in hereditary fructose intolerance.

OBJECTIVES: Hereditary fructose intolerance (HFI) is caused by aldolase B enzyme deficiency. There has been no report about HFI from Iran and the type of mutations has not been reported in the Iranian population so far. CASE PRESENTATION: Herein we report a 2 year old girl presented with failure to thrive, hepatomegaly, and liver dysfunction. The primary impression has been hepatic glycogen storage disease type 1 or 6. This diagnosis was not confirmed by laboratory data and liver biopsy. Therefore, targeted-gene sequencing (TGS) covering 450 genes involved in inborn errors in metabolic diseases was performed. The results of TGS showed a rare novel homozygous pathogenic variant c.944del (p.Gly315ValfsTer15) in the ALDOB gene. CONCLUSIONS: This report introduces a novel variant that expands the mutational spectrum of the ALDOB gene in patients with HFI.

Large Volume Paracentesis in Patients with Liver Cirrhosis Temporarily Diminishes Blood Cell Count.

Background: Large-volume paracentesis is the preferred treatment for patients with severe and refractory ascites. Several complications were reported during therapeutical paracentesis. However, there are very few published studies on the change in blood cell count after paracentesis. This study aimed to evaluate any changes in blood cell counts after ascites fluid drainage. Methods: This study was conducted on patients with severe ascites and chronic liver disease who underwent large-volume paracentesis at Namazi Hospital, in Shiraz, Iran, between March 2021 and February 2022. A data gathering form containing the patient's medical history, cause of cirrhosis, ascites fluid volume, as well as routine tests including primarily sodium, potassium, and basal creatinine, was filled out. Before and after the surgery, the total blood cell count was measured. Before the procedure, adjustment was made in the case of coagulopathy and albumin deficiency. The effect of factors such as the volume of drained fluid, splenomegaly, antibiotics, and steroid use was assessed on the changes in the number of blood cells. Using the JAMOVI 2.3.9 software, a paired t test and multiple regression were applied for statistical analysis (P<0.001). Results: The study included 37 patients. After the paracentesis procedure, the number of blood cells significantly decreased in all groups (P<0.001). The followings are the amounts of each type of blood cells before and after the procedure: Platelet=153837±91862 and 115648±69136, red blood cells=3.53±0.784 and 3.22±0.705, white blood cells=12.3±7.78 and 8.6±5.5. None of the study variables, including drained volume, splenomegaly, antibiotics, and steroid use, were significant predictors of the changes in the blood cell count after paracentesis (P>0.001). Conclusion: The findings of the present study showed that children with tense ascites who had large-volume paracentesis might experience a sharp drop in blood cell count after the procedure, which was a transient physiological condition.

Identification of a novel mutation in the PHKA2 gene in a child with liver cirrhosis.

OBJECTIVES: Glycogen storage diseases (GSDs) are heterogeneous disorders caused by various enzyme deficiencies. GSD type IX α2, the most common subtype of GSD IX, is due to a deficiency of hepatic phosphorylase kinase. Herein we will report a novel mutation in this disease with an unusual presentation. CASE PRESENTATION: we describe a 3-year-old boy who suffered from hepatomegaly, fatty liver disease, and liver cirrhosis. The cause of cirrhosis at a young age was unknown based on the laboratory data and liver biopsy, so we performed a targeted-gene sequencing (TGS) covering 450 genes involved in inborn metabolic diseases consisting of glycogen storage disorders genes with hepatic involvement. He was found out to have a rare novel pathogenic variant in the PHKA2 gene. CONCLUSIONS: This novel variant c.2226+2T > C expands the mutational spectrum of the PHKA2 gene. Also, severe liver damage (cirrhosis) in patients with GSD- IX α2 has rarely been reported, which needs further discussion. We hypothesize that unidentified PHKA2 variants may be a rare cause of childhood liver cirrhosis.

Non-invasive monitoring associated with B lymphoma cells in post-transplant lymphoproliferative disorder (PTLD) patients: Systematic review.

BACKGROUND: One of the most severe side effects of solid-organ transplantation is posttransplant lymphoproliferative disease (PTLD). People with human immunodeficiency virus infection (HIV), an immunosuppressive disease comparable to HIV, have a higher chance of developing lymphoma when their peripheral blood contains elevated levels of the immunoglobulins kappa and lambda free light chains (FLCs). METHODS: This systematic review's objective was to monitor associated B lymphoma cells in PTLD patients. In order to find relevant studies published between 1/1/2000 and 1/9/2022, two independent researchers conducted searches (MT, AJ). A literature search of English language publications was conducted using MEDLINE through PubMed, EMBASETM through Ovid, the Cochrane Library, and Trip. In addition to Magiran and SID, we searched KoreaMed and LILACS for literature published in other languages. sFLC or PTLD, transplant, or Electrophoresis are terms used in the search strategy. RESULTS: A total of 174 studies were selected. After analyzing their correspondence with the required criteria, a final review of five studies was conducted. The manuscript presents current findings on the potential benefits of the clinical applicability of sFLCs in PTLD. While the preliminary results appear promising, the only consistent result is that early-onset PTLD is predicted within the first two years after transplant, a biomarker that could be used to diagnose the condition. CONCLUSIONS: Therefore, PTLD has been predicted by using the sFLCs. There have been contradictory results to date. Future research could include assessing the quantity of sFLCs and their quality in transplant recipients. In addition to PTLD and complications after transplantation, sFLCs may provide insight into other diseases. To confirm the validity of sFLCs, more studies are needed.

Thyroid Stimulating Hormone, T3 and T4 Population-based Reference Range and Children Prevalence of Thyroid Dysfunction: First Report from South of Iran.

Background & Objective: The TSH reference range's validity affects the thyroid dysfunction diagnosis. The primary objective of this study is to determine the reference range, which is established according to age and region. Methods: The data were collected retrospectively from people over the age of one who visited Motahari Clinic for routine health checkups between August 2017 and October 2019. TSH, T4, T3, personal drug usage, and thyroid history were collected. After excluding subjects with thyroid diseases and outliers, 1392 participants were analyzed. Hormone intervals of men and women ≥1 year old have been determined using the non-parametric method. Results: The non-disease subjects' TSH, T3, and T4 reference ranges were 0.64 to 5.94 lU/mL, 0.91 to 2.47 ng/dL, and 5.53 to 12.48 g/dL, respectively. According to this range, total thyroid dysfunction prevalence in our study in children was 8.94%. There was no significant difference between TSH, T4 level, and gender in the non-disease population (P=0.46 and 0.13, respectively), but there was a statistical difference between sex and T3 (P =0.03). Our study also illustrates that for subjects under 18 years old and older, the hormones (TSH, T3, T4) concentration are statistically different (P≤0.001). Conclusion: We found a statistically difference between hormone values younger and older than age 18 (P=≤0.01); therefore, it is not appropriate to use the same reference range for children younger than age 18 and adults. There was male predominance in the population aged1-18 years old.

Development of Bio-artificial Esophageal Tissue Engineering Utilization for Circumferential Lesion Transplantation: A Narrative Review.

The esophagus is the gastrointestinal tract's primary organ that transfers bolus into the stomach with peristaltic motion. Therefore, its lesions cause a significant disturbance in the nutrition and digestive system. Esophageal disease treatment sometimes requires surgical procedures that involve removal and circumferential full-thickness replacement. Unlike other organs, the esophagus has a limited regeneration ability and cannot be transplanted from donors. There are various methods of restoring the esophageal continuity; however, they are associated with certain flaws that lead to a non-functional recovery. As an exponentially growing science, tissue engineering has become a leading technique for the development of tissue replacement to repair damaged esophageal segments. Scaffold plays a significant role in the process of tissue engineering, as it acts as a template for the regeneration of growing tissue. A variety of scaffolds have been studied to replace the esophagus. Due to the many tissue quality challenges, the results are still inadequate and need to be improved. The success of esophageal tissue regeneration will finally depend on the scaffold's capability to mimic natural tissue properties and provide a qualified environment for regeneration. Thereby, scaffold fabrication techniques are fundamental. This article reviews the recent developments in esophageal tissue engineering for the treatment of circumferential lesions based on scaffold biomaterial engineering approaches.

A pathogenic variant of TULP3 causes renal and hepatic fibrocystic disease.

Patient variants in Tubby Like Protein-3 (TULP3) have recently been associated with progressive fibrocystic disease in tissues and organs. TULP3 is a ciliary trafficking protein that links membrane-associated proteins to the intraflagellar transport complex A. In mice, mutations in Tulp3 drive phenotypes consistent with ciliary dysfunction which include renal cystic disease, as part of a ciliopathic spectrum. Here we report two sisters from consanguineous parents with fibrocystic renal and hepatic disease harboring a homozygous missense mutation in TULP3 (NM_003324.5: c.1144C>T, p.Arg382Trp). The R382W patient mutation resides within the C-terminal Tubby domain, a conserved domain required for TULP3 to associate with phosphoinositides. We show that inner medullary collecting duct-3 cells expressing the TULP3 R382W patient variant have a severely reduced ability to localize the membrane-associated proteins ARL13b, INPP5E, and GPR161 to the cilium, consistent with a loss of TULP3 function. These studies establish Arginine 382 as a critical residue in the Tubby domain, which is essential for TULP3-mediated protein trafficking within the cilium, and expand the phenotypic spectrum known to result from recessive deleterious mutations in TULP3.

Rosa damascena together with brown sugar mitigate functional constipation in children over 12 months old: A double-blind randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa × damascena Herrm., known as damask rose, is a bushy shrub that is found abundantly in Fars province, Iran. This species has been used in Iranian traditional practices for the treatment of abdominal pain and constipation, as gastrointestinal diseases. Brown sugar (Saccharum officinarum L.) has also shown laxative effects in pediatric patients with functional constipation. AIM OF STUDY: This study aimed to compare the effects of Polyethylene Glycol (PEG) and a syrup made of R. damascena and brown sugar on the treatment of functional constipation in children aged above 12 months. MATERIALS AND METHODS: This double-blind randomized clinical trial was performed on 100 patients. One group received PEG and the other received an herbal syrup containing the decocted extract of 0.1 g R. damascena petals mixed with 0.85 g brown sugar per 1 mL. The patients were followed up for two and four weeks and their progresses were recorded. RESULTS: The cure rate was 100% in the R. damascena group and 91.7% in the control group. R. damascena and brown sugar syrup had an odds ratio of 1.09 in the treatment of functional constipation compared to PEG, but the difference was not statistically significant. The only adverse effect detected in the R. damascena group after four weeks was the bad taste of the medication that was too sweet. Nonetheless, this could be solved during the pharmaceutical processes. CONCLUSION: The R. damascena extract and brown sugar syrup can be used as an effective, safe, and inexpensive agent in the treatment of functional constipation.