Spontaneous and Microbiota-Driven Degradation of Anthocyanins in an In Vitro Human Colon Model.

SCOPE: The consumption of dietary anthocyanins is associated with various health benefits. However, anthocyanins are poorly bioavailable, and most ingested anthocyanins will enter the colon where they are degraded to small phenolic metabolites that are the main absorbed forms. Little is known about the processes of anthocyanin degradation in the gut and the role of the human gut microbiota. This study aims to determine the contribution of spontaneous and microbiota-dependent degradation of anthocyanins in the human colon. METHODS AND RESULTS: Purified anthocyanin extracts from black rice and bilberry were incubated in an in vitro human fecal-inoculated pH-controlled colon model over 24 h and anthocyanins were analyzed using HPLC-DAD. The study shows that the loss of anthocyanins occurs both spontaneously and as a consequence of metabolism by the gut microbiota. The study observes that there is high variability in spontaneous degradation but only modest variation in total degradation, which included the microbiota-dependent component. The degradation rate of anthocyanins is also shown to be dependent on the B-ring substitution pattern and the type of sugar moiety, both for spontaneous and microbiota-dependent degradation. CONCLUSION: Anthocyanins are completely degraded in a model of the human colon by a combination of spontaneous and microbiota-dependent processes.

Outcome and complications after surgery for thyroid carcinoma in pediatric age-an evaluation of practice.

OBJECTIVES: To discuss management protocol, surgical complications, and outcomes of thyroid carcinoma in children. METHODS: We performed a retrospective analysis including all pediatric patients with thyroid carcinoma who were managed at our institution between January 2011 and January 2021. Data were analyzed regarding demographics, clinical features, operative details, postoperative complications, and survival data. RESULTS: Thirty-two patients were identified; 26 females (81.25%) and 6 males (18.75%). The median age at operation was 14 years (range: 5-18). Twenty-six (81.25%) patients presented with palpable thyroid swelling. Median tumor size was 3 cm (range: 1-7). Metastatic workup did not detect any pulmonary metastases. Total thyroidectomy was performed in 25 patients (78%), and 16 of them underwent additional bilateral neck dissection (16 had central nodal dissection, and 7 had both central and lateral nodal dissection). Seven patients (22%) underwent hemithyroidectomy, and only one of them had a completion thyroidectomy after 2 weeks. Conservative resection was adopted in six children with similar criteria (tumor size < 1.5 cm in one lobe, no extrathyroid extension, differentiated thyroid carcinoma, no detected lymph nodes). Postoperative complications occurred in eight patients (all had total thyroidectomy) with an overall incidence of 25%. Seven patients had transient morbidities that were managed conservatively (chylous leak n = 1, hypoparathyroidism n = 3, and nerve palsy n = 3). At a median follow-up time of 54 months, four patients had relapsed (all underwent total thyroidectomy). The 5-year OS and EFS were 100% and 87.5%, respectively. CONCLUSION: Operative resection for pediatric thyroid carcinoma can be performed with average short-term complications and achieving excellent outcomes. Total thyroidectomy remains the standard procedure of choice in the majority of those patients. However, conservative surgery can be successfully adopted in a well-selected group of children with favorable long-term results as per our findings.

Microbiomes in physiology: insights into 21st-century global medical challenges.

NEW FINDINGS: What is the topic of this review? The role of the gut microbiome in physiology and how it can be targeted as an effective strategy against two of the most important global medical challenges of our time, namely, metabolic diseases and antibacterial resistance. What advances does it highlight? The critical roles of the microbiome in regulating host physiology and how microbiome analysis is useful for disease stratification to enable informed clinical decisions and develop interventions such as faecal microbiota transplantation, prebiotics and probiotics. Also, the limitations of microbiome modulation, including the potential for probiotics to enhance antimicrobial resistance gene reservoirs, and that currently a 'healthy microbiome' that can be used as a biobank for transplantation is yet to be defined. ABSTRACT: The human gut microbiome is a key factor in the development of metabolic diseases and antimicrobial resistance, which are among the greatest global medical challenges of the 21st century. A recent symposium aimed to highlight state-of-the-art evidence for the role of the gut microbiome in physiology, from childhood to adulthood, and the impact this has on global disease outcomes, ageing and antimicrobial resistance. Although the gut microbiome is established early in life, over time the microbiome and its components including metabolites can become perturbed due to changes such as dietary habits, use of antibiotics and age. As gut microbial metabolites, including short-chain fatty acids, secondary bile acids and trimethylamine-N-oxide, can interact with host receptors including G protein-coupled receptors and can alter host metabolic fluxes, they can significantly affect physiological homoeostasis leading to metabolic diseases. These metabolites can be used to stratify disease phenotypes such as irritable bowel syndrome and adverse events after heart failure and allow informed decisions on clinical management and treatment. While strategies such as use of probiotics, prebiotics and faecal microbiota transplantation have been proposed as interventions to treat and prevent metabolic diseases and antimicrobial resistance, caution must be exercised, first due to the potential of probiotics to enhance antimicrobial resistance gene reservoirs, and second, a 'healthy gut microbiome' that can be used as a biobank for transplantation is yet to be defined. We highlight that sampling other parts of the gastrointestinal tract may produce more representative data than the faecal microbiome alone.

Development and Validation of a LC-MS/MS Technique for the Analysis of Short Chain Fatty Acids in Tissues and Biological Fluids without Derivatisation Using Isotope Labelled Internal Standards.

The gut microbiota is critical to the maintenance of physiological homeostasis and as such is implicated in a range of diseases such as colon cancer, ulcerative colitis, diabetes, cardiovascular diseases, and neurodegenerative diseases. Short chain fatty acids (SCFAs) are key metabolites produced by the gut microbiota from the fermentation of dietary fibre. Here we present a novel, sensitive, and direct LC-MS/MS technique using isotopically labelled internal standards without derivatisation for the analysis of SCFAs in different biological matrices. The technique has significant advantages over the current widely used techniques based on sample derivatization and GC-MS analysis, including fast and simple sample preparation and short LC runtime (10 min). The technique is specific and sensitive for the quantification of acetate, butyrate, isobutyrate, isovalerate, lactate, propionate and valerate. The limits of detection were all 0.001 mM except for acetate which was 0.003 mM. The calibration curves for all the analytes were linear with correlation coefficients r2 > 0.998. The intra- and inter-day precisions in three levels of known concentrations were <12% and <20%, respectively. The quantification accuracy ranged from 92% to 120%. The technique reported here offers a valuable analytical tool for use in studies of SCFA production in the gut and their distribution to host tissues.

The use of an in-vitro batch fermentation (human colon) model for investigating mechanisms of TMA production from choline, L-carnitine and related precursors by the human gut microbiota.

PURPOSE: Plasma trimethylamine-N-oxide (TMAO) levels have been shown to correlate with increased risk of metabolic diseases including cardiovascular diseases. TMAO exposure predominantly occurs as a consequence of gut microbiota-dependent trimethylamine (TMA) production from dietary substrates including choline, carnitine and betaine, which is then converted to TMAO in the liver. Reducing microbial TMA production is likely to be the most effective and sustainable approach to overcoming TMAO burden in humans. Current models for studying microbial TMA production have numerous weaknesses including the cost and length of human studies, differences in TMA(O) metabolism in animal models and the risk of failing to replicate multi-enzyme/multi-strain pathways when using isolated bacterial strains. The purpose of this research was to investigate TMA production from dietary precursors in an in-vitro model of the human colon. METHODS: TMA production from choline, L-carnitine, betaine and γ-butyrobetaine was studied over 24-48 h using an in-vitro human colon model with metabolite quantification performed using LC-MS. RESULTS: Choline was metabolised via the direct choline TMA-lyase route but not the indirect choline-betaine-TMA route, conversion of L-carnitine to TMA was slower than that of choline and involves the formation of the intermediate γ-BB, whereas the Rieske-type monooxygenase/reductase pathway for L-carnitine metabolism to TMA was negligible. The rate of TMA production from precursors was choline > carnitine > betaine > γ-BB. 3,3-Dimethyl-1-butanol (DMB) had no effect on the conversion of choline to TMA. CONCLUSION: The metabolic routes for microbial TMA production in the colon model are consistent with observations from human studies. Thus, this model is suitable for studying gut microbiota metabolism of TMA and for screening potential therapeutic targets that aim to attenuate TMA production by the gut microbiota. TRIAL REGISTRATION NUMBER: NCT02653001 ( http://www.clinicaltrials.gov ), registered 12 Jan 2016.

Topical application of tranexamic acid after adenoidectomy: a double-blind, prospective, randomized, controlled study.

OBJECTIVE: Is to evaluate the efficacy of tranexamic acid when applied locally in children after primary isolated adenoidectomy with respect to intra-operative blood loss and post-operative bleeding. STUDY DESIGN: Prospective, double-blind, randomized, controlled trial. SETTING: Otolaryngology department, Tanta University and Tiba Hospitals, Egypt. PATIENTS AND METHODS: Over three years, 400 children underwent primary isolated adenoidectomy followed by topical application of tranexamic acid (tranexamic acid group, 200 children) or saline (Placebo group, 200 children) with at least two weeks' follow up. Intra-operative blood loss and post-operative hemorrhage were monitored. RESULTS: Both groups were almost equivalent in age and gender. The frequency of primary post-adenoidectomy hemorrhage as well as the rate of postnasal packing and blood transfusion required to manage severe bleeding were higher in placebo group. The volume of blood loss during surgery showed significant reduction in tranexamic acid group. CONCLUSION: Topical application of tranexamic acid after adenoidectomy led to a significant reduction in blood loss during surgery and decreasing in the rate of post-operative bleeding as well as the need for postnasal packing and blood transfusion.

Mitomycin C-enhanced revision endoscopic dacryocystorhinostomy: a prospective randomized controlled trial.

OBJECTIVES: (1) To conduct an adequately powered randomized controlled trial investigating the safety and efficacy of mitomycin C-enhanced revision endoscopic dacryocystorhinostomy (DCR) and (2) to analyze causes of failure after primary endoscopic DCR. STUDY DESIGN: A randomized controlled study. SETTING: General hospital. SUBJECTS AND METHODS: Seventy-six revision endoscopic DCRs were randomized into 2 groups: endoscopic DCR with mitomycin (group I), where 0.5 mg/mL mitomycin C was applied for 10 minutes, and endoscopic DCR without mitomycin (group II). Follow-up settings were done to document the patient's subjective improvement, to judge ostium patency on irrigation, and to record any complications. RESULTS: Causes of failure in the original 92 patients included canalicular obstruction (14%), small misplaced bony window (43%), very small nasolacrimal stoma due to development of synechia (23%), and complete closure of nasolacrimal stoma with tough fibrous tissue (63%). There was no significant difference between the 2 groups in subjective and objective success rates and adverse events. Group I demonstrated a significantly longer operative time and a significantly lower number of debridement sessions (mean of 1.2 vs 1.9). CONCLUSIONS: Recurrent nasolacrimal duct obstruction after primary endoscopic DCR is mainly due to reclosure of the nasolacrimal stoma with synechia and fashioning of the small misplaced bony window. Mitomycin C does not increase the success rate of revision endoscopic DCR. It is a safe procedure and may be of value only in patients inaccessible to strict follow-up because it induces a better healing profile in terms of mucosal recovery, wound healing, and less need for debridement sessions.

Telescopic-assisted radiofrequency adenoidectomy: a prospective randomized controlled trial.

OBJECTIVES/HYPOTHESIS: The objective was to conduct a prospective randomized controlled trial describing and investigating the efficacy and safety of transoral telescopic-assisted radiofrequency adenoidectomy in young children. STUDY DESIGN: Prospective randomized controlled trial. METHODS: One hundred twenty patients who were 36 months of age or less and planned to undergo adenoidectomy or adenoidectomy with insertion of tympanostomy tubes were included in the study. Children were prospectively and randomly assigned into two equal treatment groups: the telescopic-assisted adenoidectomy using radiofrequency curette and the conventional adenoid-curette adenoidectomy. The main parameters included visual analogue scale score for nasal breathing, amount of blood loss, operating time, completeness of adenoid resection, smoothness of postoperative recovery, and complications. RESULTS: Both groups had a significant improvement in the visual analogue scale score after surgery with no evidence for a significant difference between the conventional adenoid-curette and radiofrequency groups. The amount of blood lost during radiofrequency adenoidectomy was minimal, with a mean difference of 31 mL and a median difference of 26 mL. There was a tendency for shorter operative time in the radiofrequency group, but this did not reach a statistical significance. No evidence for a significant difference was noticed in the smoothness of postoperative recovery or complication rate. CONCLUSION: Telescopic-assisted radiofrequency-curette adenoidectomy allows removal of huge adenoids completely in a precise, easy, and cost-effective procedure, with minimal blood loss and short operating time. The use of transoral telescopes provides a clear visualization that helps complete removal of the adenoids, reduction of unnecessary trauma, and effective control of bleeding.