Colon cancer associated transcript-1 (CCAT1) expression in adenocarcinoma of the stomach

Background: Long non-coding RNAs (lncRNAs) have been shown to have functional roles in cancer biology and are dys-regulated in many tumors. Colon Cancer Associated Transcript -1 (CCAT1) is a lncRNA, previously shown to be significantly up-regulated in colon cancer. The aim of this study is to determine expression levels of CCAT1 in gastric carcinoma (GC). Methods: Tissue samples were obtained from patients undergoing resection for gastric carcinoma (n=19). For each patient, tumor tissue and normal appearing gastric mucosa were taken. Normal gastric tissues obtained from morbidly obese patients, undergoing laparoscopic sleeve gastrectomy served as normal controls (n=19). A human gastric carcinoma cell line (AGS) served as positive control. RNA was extracted from all tissue samples and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR). Results: Low expression of CCAT1 was identified in normal gastric mucosa samples obtained from morbidly obese patients [mean Relative Quantity (RQ) = 1.95±0.4]. AGS human gastric carcinoma cell line showed an elevated level of CCAT1 expression (RQ=8.02). Expression levels of CCAT1 were approximately 10.8 fold higher in GC samples than in samples taken from the negative control group (RQ=21.1±5 vs. RQ=1.95±0.4, respectively, p<0.001). Interestingly, CCAT1 expression was significantly overexpressed in adjacent normal tissues when compared to the negative control group (RQ = 15.25±2 vs. RQ=1.95±0.4, respectively, p<0.001). Tissues obtained from recurrent GC cases showed the highest expression levels (RQ = 88.8±31; p<0.001). Expression levels increased with tumor stage (T4- 36.4±15, T3- 16.1±6, T2- 4.7±1), however this did not reach statistical significance (p=0.2). There was no difference in CCAT1 expression between intestinal and diffuse type GC (RQ=22.4±7 vs. 22.4±16, respectively, p=0.9). Within the normal gastric tissue samples, no significant difference in CCAT1 expression was observed in helicobacter pylori negative and positive patients (RQ= 2.4±0.9 vs. 0.93±0.2, respectively, p=0.13). Conclusion: CCAT1 is up-regulated in gastric cancer, and may serve as a potential bio-marker for early detection and surveillance. © Ivyspring International Publisher

Diagnosis of Cystic Fibrosis in Screened Populations

Objective Cystic fibrosis (CF) can be difficult to diagnose, even when newborn screening (NBS) tests yield positive results. This challenge is exacerbated by the multitude of NBS protocols, misunderstandings about screening vs diagnostic tests, and the lack of guidelines for presumptive diagnoses. There is also confusion regarding the designation of age at diagnosis. Study design To improve diagnosis and achieve standardization in definitions worldwide, the CF Foundation convened a committee of 32 experts with a mission to develop clear and actionable consensus guidelines on diagnosis of CF with an emphasis on screened populations, especially the newborn population. A comprehensive literature review was performed with emphasis on relevant articles published during the past decade. Results After reviewing the common screening protocols and outcome scenarios, 14 of 27 consensus statements were drafted that apply to screened populations. These were approved by 80% or more of the participants. Conclusions It is recommended that all diagnoses be established by demonstrating dysfunction of the CF transmembrane conductance regulator (CFTR) channel, initially with a sweat chloride test and, when needed, potentially with newer methods assessing membrane transport directly, such as intestinal current measurements. Even in babies with 2 CF-causing mutations detected via NBS, diagnosis must be confirmed by demonstrating CFTR dysfunction. The committee also recommends that the latest classifications identified in the Clinical and Functional Translation of CFTR project [http://www.cftr2.org/index.php] should be used to aid with CF diagnosis. Finally, to avoid delays in treatment, we provide guidelines for presumptive diagnoses and recommend how to determine the age of diagnosis

Challenging the diagnosis of Cystic Fibrosis in a patient carrying the 186-8T/C allelic variant in the CF Transmembrane Conductance Regulator gene

BACKGROUND: This report describe for the first time a clinical case with a CFTR allelic variant 186-8T/C (c.54-8 T/C) in intron 1 of CFTR and underline the importance of applying a combination of genetic and functional tests to establish or exclude a diagnosis of Cystic Fibrosis. In this case the diagnostic algorithm proposed for CF has been successfully applied at our Center and previous CF diagnosis assigned in a different Center was not confirmed.Case report: A 38 year-old Italian woman had been treated as affected by CF since 2010, following diagnosis based on sweat tests (reported values of 73 and 57 mEq/L) and a clinical history consistent with CF. No mutations were identified by first level of genetic analysis. Afterwards the patient referred to our center for assessing the relevance of these findings. The genetic variant 186-8T/C (c.54-8 T/C) in intron 1 of the CFTR gene was detected by sequencing. Low-level interstitial-alveolar infiltration was recorded by high-resolution computerized tomography. Lung function was normal and sputum and Broncho Alveolar Lavage cultures resulted bacteriologically negative. Sweat chloride levels was re-assessed and resulted with values of 57 and 35 mEq/L, with a borderline range between 40 and 60 mEq/L. Nasal Potential Difference measurements resulted in three reliable measurements consistent with a non-CF phenotype. Differential diagnosis with ciliary dyskinesia was excluded, as was exon 2 skipping of CFTR gene that might have caused a CFTR functional defect. Furthermore, single cell fluorescence analysis in response to cAMP agonists performed in patient's monocytes overlapped those obtained in healthy donors. CONCLUSION: We concluded that this patient was not affected by CF. This case highlights the need for referrals to highly specialized centers and the importance of combined functional and genetic tests in making a correct diagnosis. Moreover, we confirmed a correlation between NPD tracings and cell depolarization in monocytes providing a rationale for proposing the use of leukocytes as a potential support for CF diagnosis

Impact of Obesity on Pediatric Acute Recurrent and Chronic Pancreatitis

OBJECTIVE: The aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP). METHODS: We determined body mass index (BMI) status at enrollment in INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort using CDC criteria for pediatric-specific BMI percentiles. We used the Cochran-Armitage test to assess trends and the Jonckheere-Terpstra test to determine associations. RESULTS: Of 446 subjects (acute recurrent pancreatitis, n = 241; CP, n = 205), 22 were underweight, 258 normal weight, 75 overweight, and 91 were obese. The BMI groups were similar in sex, race, and age at presentation. Hypertriglyceridemia was more common in overweight or obese. Obese children were less likely to have CP and more likely to have acute inflammation on imaging. Compared with children with normal weight, obese or overweight children were older at first acute pancreatitis episode and diagnosed with CP at an older age. Obese or overweight children were less likely to undergo medical or endoscopic treatment, develop exocrine pancreatic insufficiency, and require total pancreatectomy with islet autotransplantation. Diabetes was similar among all groups. CONCLUSIONS: Obesity or overweight seems to delay the initial acute pancreatitis episode and diagnosis of CP compared with normal weight or underweight. The impact of obesity on pediatric CP progression and severity deserves further study

The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy

The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested.Portuguese Foundation for Science and Technology (FCT), the strategic funding of UID/BIO/04469/2013-CEB and UID/EQU/00511/2013-LEPABE units. This study was also supported by FCT and the European Community fund FEDER, through Program COMPETE, under the scope of the Projects “DNA mimics” PIC/IC/82815/2007, RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462), “BioHealth—Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124-FEDER-000027 and NORTE-07-0124-FEDER-000025—RL2_ Environment and Health, co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER. The authors also acknowledge the grant of Susana P. Lopes (SFRH/BPD/95616/2013) and of the COST-Action TD1004: Theragnostics for imaging and therapy

European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for the evaluation and treatment of gastrointestinal and nutritional complications in children with neurological impairment

OBJECTIVES: Feeding difficulties are frequent in children with neurological impairments and can be associated with undernutrition, growth failure, micronutrients deficiencies, osteopenia and nutritional comorbidites. Gastrointestinal problems including gastroesophageal reflux disease, constipation and dysphagia are also very frequent in this population and impact quality of life and nutritional status. There is currently a lack of a systematic approach to the care of these patients. With this report, ESPGHAN aims to develop uniform guidelines for the management of the gastroenterological and nutritional problems in neurologically impaired chidren. METHODS: Thirty-one clinical questions addressing the diagnosis, treatment, and prognosis of common gastrointestinal and nutritional problems in neurological impaired children were formulated. Questions aimed to assess: 1) the nutritional management including nutritional status, identifying undernutrition, monitoring nutritional status, and defining nutritional requirements; 2) to classify gastrointestinal issues including oropharyngeal dysfunctions, motor and sensory function, gastroesophageal reflux disease, and constipation; 3) to evaluate the indications for nutritional rehabilitation including enteral feeding and percutaneous gastrostomy/jejunostomy; 4) to define indications for surgical interventions (e.g. Nissen Fundoplication, oesophago-gastric disconnection) and finally 5) to consider ethical issues related to digestive and nutritional problems in the severely neurologically impaired children. A systematic literature search was performed from 1980 to October 2015 using MEDLINE. The approach of the Grading of Recommendations Assessment, Development and Evaluation was applied to evaluate the outcomes. During two consensus meetings, all recommendations were discussed and finalized. The group members voted on each recommendation using the nominal voting technique. Expert opinion was applied to support the recommendations where no randomized controlled trials were available

Cystic fibrosis presenting as recurrent pancreatitis in a young child with a normal sweat test and pancreas divisum: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pancreatitis is a rare manifestation of cystic fibrosis (CF) and may rarely be the presenting symptom in adolescent or adult patients with CF. We report a case of a 4 year-old female who initially presented with recurrent pancreatitis, a normal sweat test, and a diagnosis of pancreas divisum. She was subsequently diagnosed with cystic fibrosis at the age of 6 years, despite normal growth and no pulmonary symptoms, after nasal potential difference measurements suggested possible CF and two known CF-causing mutations (ΔF508 and L997F) were detected.</p> <p>Case Presentation</p> <p>An otherwise healthy 4 year-old female developed chronic pancreatitis and was diagnosed with pancreas divisum. Sphincterotomy was performed without resolution of her pancreatitis. Sweat test was negative for cystic fibrosis, but measurement of nasal potential differences suggested possible cystic fibrosis. These results prompted extended Cystic Fibrosis Transmembrane Regulator Conductance (CFTR) mutational analysis that revealed a compound heterozygous mutation: ΔF508 and L997F.</p> <p>Conclusion</p> <p>CFTR mutations should be considered in cases of chronic or recurrent pancreatitis despite a negative sweat test and the presence of pancreas divisum. Children with CFTR mutations may present with recurrent pancreatitis, lacking any other signs or symptoms of cystic fibrosis. It is possible that the combination of pancreas divisum and abnormal CFTR function may contribute to the severity and frequency of recurrent pancreatitis.</p

Aminoglycoside antibiotics and autism: a speculative hypothesis

BACKGROUND: Recently, it has been suspected that there is a relationship between therapy with some antibiotics and the onset of autism; but even more curious, some children benefited transiently from a subsequent treatment with a different antibiotic. Here, we speculate how aminoglycoside antibiotics might be associated with autism. PRESENTATION: We hypothesize that aminoglycoside antibiotics could a) trigger the autism syndrome in susceptible infants by causing the stop codon readthrough, i.e., a misreading of the genetic code of a hypothetical critical gene, and/or b) improve autism symptoms by correcting the premature stop codon mutation in a hypothetical polymorphic gene linked to autism. TESTING: Investigate, retrospectively, whether a link exists between aminoglycoside use (which is not extensive in children) and the onset of autism symptoms (hypothesis "a"), or between amino glycoside use and improvement of these symptoms (hypothesis "b"). Whereas a prospective study to test hypothesis "a" is not ethically justifiable, a study could be designed to test hypothesis "b". IMPLICATIONS: It should be stressed that at this stage no direct evidence supports our speculative hypothesis and that its main purpose is to initiate development of new ideas that, eventually, would improve our understanding of the pathobiology of autism

Pancreas transplantation for Cystic Fibrosis: A Frequently Missed Opportunity

Cystic fibrosis (CF) is an inherited autosomal recessive disorder. Despite optimized therapy, the majority of affected individuals ultimately die of respiratory failure. As patients with CF are living longer, extra-pulmonary manifestations may develop including pancreatic failure, which manifests as exocrine insufficiency, and CF related diabetes (CFRD). Both of these can be managed through pancreas transplantation. Pancreas transplantation is usually performed in combination with another organ, most often with a kidney transplant for end-stage diabetic nephropathy. In the CF patient population, the two settings where inclusion of a pancreas transplant should be considered would be in combination with a lung transplant for CF pulmonary disease, or in combination with a liver for CF related liver disease with cirrhosis. This report will discuss this topic in detail, including a review of the literature regarding combinations of lung/pancreas and liver/pancreas transplant