Implementation and participation of an online nutrition curriculum for pediatric gastroenterology fellows.

Our team of nutrition experts developed an online nutrition curriculum consisting of 21 modules to serve as a resource for a stand-alone nutrition curriculum or as a supplement to existing nutrition electives during the Pediatric Gastroenterology fellowship. From April 2020 through January 2023, 2090 modules were completed by 436 fellows from 75 different programs across North America. The program was accessed most during tight restrictions on in-person learning during the COVID-19 pandemic. Overall, participants posttest scores improved from baseline pretest scores indicating retention of information from the modules. The overall success of this program suggests that there should be continued efforts to develop and offer online learning opportunities in clinical nutrition. There is an opportunity to expand the audience for the curriculum to include pediatric gastroenterologists from across the globe.

Optimizing the physical properties of collagen/hyaluronan hydrogels by inhibition of polyionic complexes formation at pH close to the collagen isoelectric point.

Collagen/hyaluronan hydrogels with physical properties well suited for biomedical applications are challenging to synthesize due to the formation of polyionic complexes (PICs). A systematic physicochemical study was thus performed to determine novel conditions to inhibit the formation of collagen/hyaluronan PICs and obtain composite hydrogels with high physical properties. Using a range of pH from 1 to 5.5 and the addition of NaCl, type I collagen and tyramine-substituted hyaluronic acid (THA) solutions were mixed and analyzed by cryo-scanning electron microscopy and ATR-FTIR. PIC formation was inhibited at pH 1 without salt and at pH 2.5 and 5.5 in the presence of 400 mM NaCl. Interestingly, collagen fibrils were observed in solution at pH 5.5 before mixing with THA. After collagen gelling by pH increase, a homogeneous hydrogel consisting of collagen fibrils was only observed when PICs were inhibited. Then, the THA gelling performed by photo-crosslinking increased the rheological properties by four when hydrogels were formed with collagen/THA mixtures at pH 1 or 5.5 with salt. Taken together, these results show that a pH of 5.5, close to the collagen isoelectric point, enables the formation of collagen fibrils in solution, inhibits the PICs formation, and allows the formation of homogenous collagen/THA composite hydrogels compatible with cell survival.

Chronic Mucosal Inflammation in Pediatric Intestinal Failure Patients-A Unique Phenomenon.

INTRODUCTION/OBJECTIVES: As intestinal failure (IF) management improves and long-term survival rate increases, its physiological complications have become more apparent. The development of chronic intestinal inflammation resembling inflammatory bowel disease (IBD) in this population has been reported, but the literature describing it in detail is sparse. The present study was designed to characterize children with IF who developed chronic intestinal inflammation and identify the potential predisposing clinical factors. METHODS: This retrospective study was based on the electronic medical records of pediatric patients seen at the Cincinnati Children's Hospital Medical Center between January 2000 and July 2022. Demographic and medical history data were collected and compared between children with IF that developed chronic intestinal inflammation and children with IF that did not develop chronic intestinal inflammation. RESULTS: During the follow-up period, 23 children were diagnosed with chronic intestinal inflammation. Of these, 12 (52%) were males, with a median age of 4.5 (3-7) years at diagnosis. Nearly one-third of the patients had gastroschisis (31%), followed by necrotizing enterocolitis (26%), and malrotation and volvulus (21.7%). More children in the chronic intestinal inflammation group lacked an ileocecal valve (ICV) and adjoining distal ileum as compared to the short bowel syndrome (SBS)-IF control group (15 patients, 65% vs 8 patients, 33%). Moreover, more children in the chronic intestinal inflammation group had undergone a prior lengthening procedure than the SBS-IF control group (5 patients, 21.7% vs. 0, respectively). DISCUSSION: SBS patients are at risk of relatively early onset chronic intestinal inflammation. The absence of an ICV (and adjoin ileum) and prior lengthening procedures emerge as factors associated with the risk of IBD in these patients.

Evaluation and Management of Iron Deficiency in Children Undergoing Intestinal Rehabilitation-A Position Paper From the NASPGHAN Intestinal Rehabilitation Special Interest Group.

Iron deficiency (ID) is the most common nutritional deficiency affecting children undergoing intestinal rehabilitation (IR). Patients may be asymptomatic or present with nonspecific symptoms including fatigue, irritability, and dizziness. The diagnosis of ID in this population can be complicated by the coexistence of systemic inflammation or other nutritional deficiencies which may mimic ID. Many routinely available laboratory tests lack specificity and no consensus on screening is available. Success in oral and enteral treatment is impeded by poor tolerance of iron formulations in a population already challenged with intolerance. Newer parenteral iron formulations exhibit excellent safety profiles, but their role in repletion in this population remains unclear. The following report, compiled by a multidisciplinary group of providers caring for children undergoing IR and representing the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Special Interest Group for Intestinal Rehabilitation, seeks to address these challenges. After discussing iron physiology and population-specific pathophysiology, we make recommendations on iron intake, iron status assessment, and evaluation for alternative causes of anemia. We then provide recommendations on iron supplementation and treatment of ID anemia specific to this nutritionally vulnerable population.

Bio-Prospecting of Crude Leaf Extracts from Thirteen Plants of Brazilian Cerrado Biome on Human Glioma Cell Lines.

(1) Background: Malignant gliomas are aggressive tumors characterized by fast cellular growth and highly invasive properties. Despite all biological and clinical advances in therapy, the standard treatment remains essentially palliative. Therefore, searching for alternative therapies that minimize adverse symptoms and improve glioblastoma patients' outcomes is imperative. Natural products represent an essential source in the discovery of such new drugs. Plants from the cerrado biome have been receiving increased attention due to the presence of secondary metabolites with significant therapeutic potential. (2) Aim: This study provides data on the cytotoxic potential of 13 leaf extracts obtained from plants of 5 families (Anacardiaceae, Annonaceae, Fabaceae, Melastomataceae e Siparunaceae) found in the Brazilian cerrado biome on a panel of 5 glioma cell lines and one normal astrocyte. (3) Methods: The effect of crude extracts on cell viability was evaluated by MTS assay. Mass spectrometry (ESI FT-ICR MS) was performed to identify the secondary metabolites classes presented in the crude extracts and partitions. (4) Results: Our results revealed the cytotoxic potential of Melastomataceae species Miconia cuspidata, Miconia albicans, and Miconia chamissois. Additionally, comparing the four partitions obtained from M. chamissois crude extract indicates that the chloroform partition had the greatest cytotoxic activity against the glioma cell lines. The partitions also showed a mean IC50 close to chemotherapy, temozolomide; nevertheless, lower toxicity against normal astrocytes. Analysis of secondary metabolites classes presented in these crude extracts and partitions indicates the presence of phenolic compounds. (5) Conclusions: These findings highlight M. chamissois chloroform partition as a promising component and may guide the search for the development of additional new anticancer therapies.

Demographically diverse crowds are typically not much wiser than homogeneous crowds.

Averaging independent numerical judgments can be more accurate than the average individual judgment. This "wisdom of crowds" effect has been shown with large, diverse samples, but the layperson wishing to take advantage of this may only have access to the opinions of a small, more demographically homogeneous "convenience sample." How wise are homogeneous crowds relative to diverse crowds? In simulations and survey studies, we demonstrate three necessary conditions under which small socially diverse crowds can outperform socially homogeneous crowds: Social identity must predict judgment, the effect of social identity on judgment must be at least moderate in size, and the average estimates of the social groups in question must "bracket" the truth being judged. Seven survey studies suggest that these conditions are rarely met in real judgment tasks. Comparisons between the performances of diverse and homogeneous crowds further confirm that social diversity can make crowds wiser but typically by a very small margin.

Bioprospecting of Natural Compounds from Brazilian Cerrado Biome Plants in Human Cervical Cancer Cell Lines.

Cervical cancer is the third most common in Brazilian women. The chemotherapy used for the treatment of this disease can cause many side effects; then, to overcome this problem, new treatment options are necessary. Natural compounds represent one of the most promising sources for the development of new drugs. In this study, 13 different species of 6 families from the Brazilian Cerrado vegetation biome were screened against human cervical cancer cell lines (CCC). Some of these species were also evaluated in one normal keratinocyte cell line (HaCaT). The effect of crude extracts on cell viability was evaluated by a colorimetric method (MTS assay). Extracts from Annona crassiflora, Miconia albicans, Miconia chamissois, Stryphnodendron adstringens, Tapirira guianensis, Xylopia aromatica, and Achyrocline alata showed half-maximal inhibitory concentration (IC50) values < 30 µg/mL for at least one CCC. A. crassiflora and S. adstringens extracts were selective for CCC. Mass spectrometry (Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (ESI FT-ICR MS)) of A. crassiflora identified fatty acids and flavonols as secondary compounds. One of the A. crassiflora fractions, 7C24 (from chloroform partition), increased H2AX phosphorylation (suggesting DNA damage), PARP cleavage, and cell cycle arrest in CCC. Kaempferol-3-O-rhamnoside and oleic acid were bioactive molecules identified in 7C24 fraction. These findings emphasize the importance of investigating bioactive molecules from natural sources for developing new anti-cancer drugs.

From byproduct to a functional ingredient: Camu-camu (Myrciaria dubia) seed extract as an antioxidant agent in a yogurt model.

This work aimed to characterize the phenolic composition and in vitro antioxidant and antiproliferative properties of lyophilized camu-camu (Myrciaria dubia) seed extract (LCE), and to assess the effects of LCE on the antioxidant and sensory traits of yogurt. The LCE contained 46.3% (wt/wt) total phenolic content; the main compounds quantified were vescalagin, castalagin, gallic acid, procyanidin A2, and (-)-epicatechin. The LCE had antioxidant activity, as measured by different chemical assays (2,2-diphenyl-1-picrylhydrazyl, Folin-Ciocalteu reducing capacity, total reducing capacity, ferric reducing antioxidant power, and Cu2+ chelating capacity), and inhibited the cell proliferation of HepG2 cells (human hepatoma carcinoma; IC50 = 1,116 µg/mL) and Caco-2 cells (human colorectal adenocarcinoma epithelial cells; IC50 = 608.5 µg/mL). In addition, LCE inhibited the in vitro activity of α-amylase, α-glucosidase, and angiotensin-converting enzyme, and protected DNA from peroxyl radical-induced scission. When added to yogurts, different concentrations of LCE (0, 0.25, 0.5, 0.75, and 1.0 g/100 g) increased the chemical antioxidant and reducing capacities. The camu-camu yogurt containing LCE at 0.25 g/100 g had an acceptance index of 84%, showing that camu-camu seed extract may be a potential ingredient for addition to yogurts.

Serotonergic signalling suppresses ataxin 3 aggregation and neurotoxicity in animal models of Machado-Joseph disease.

Polyglutamine diseases are a class of dominantly inherited neurodegenerative disorders for which there is no effective treatment. Here we provide evidence that activation of serotonergic signalling is beneficial in animal models of Machado-Joseph disease. We identified citalopram, a selective serotonin reuptake inhibitor, in a small molecule screen of FDA-approved drugs that rescued neuronal dysfunction and reduced aggregation using a Caenorhabditis elegans model of mutant ataxin 3-induced neurotoxicity. MOD-5, the C. elegans orthologue of the serotonin transporter and cellular target of citalopram, and the serotonin receptors SER-1 and SER-4 were strong genetic modifiers of ataxin 3 neurotoxicity and necessary for therapeutic efficacy. Moreover, chronic treatment of CMVMJD135 mice with citalopram significantly reduced ataxin 3 neuronal inclusions and astrogliosis, rescued diminished body weight and strikingly ameliorated motor symptoms. These results suggest that small molecule modulation of serotonergic signalling represents a promising therapeutic target for Machado-Joseph disease.

Glucocorticoid receptor-dependent therapeutic efficacy of tauroursodeoxycholic acid in preclinical models of spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is an adult-onset neurodegenerative disease caused by a polyglutamine expansion in the ataxin-3 (ATXN3) gene. No effective treatment is available for this disorder, other than symptom-directed approaches. Bile acids have shown therapeutic efficacy in neurodegenerative disease models. Here, we pinpointed tauroursodeoxycholic acid (TUDCA) as an efficient therapeutic, improving the motor and neuropathological phenotype of SCA3 nematode and mouse models. Surprisingly, transcriptomic and functional in vivo data showed that TUDCA acts in neuronal tissue through the glucocorticoid receptor (GR), but independently of its canonical receptor, the farnesoid X receptor (FXR). TUDCA was predicted to bind to the GR, in a similar fashion to corticosteroid molecules. GR levels were decreased in disease-affected brain regions, likely due to increased protein degradation as a consequence of ATXN3 dysfunction being restored by TUDCA treatment. Analysis of a SCA3 clinical cohort showed intriguing correlations between the peripheral expression of GR and the predicted age at disease onset in presymptomatic subjects and FKBP5 expression with disease progression, suggesting this pathway as a potential source of biomarkers for future study. We have established a novel in vivo mechanism for the neuroprotective effects of TUDCA in SCA3 and propose this readily available drug for clinical trials in SCA3 patients.