Generation of patient-specific iPSCs for Hirschsprung's disease modelling

DMM 2011 entitled: Re-engineering Regenerative MedicineLocal Scholarship Awardees - Poster Sessions: no. 6Hirschsprung’s (HSCR) disease is a congenital disorder of the colon in which certain nerve cells are absent due to incomplete colonization of bowel with enteric neural crest (NC) cells, causing chronic constipation. RET gene encodes for a tyrosine kinase receptor and is highly implicated in the neural crest development. Mutations or genetic variants in RET have accounted for most of the HSCR cases. In particular, a single nucleotide polymorphisms (SNP, rs2435362) residing in the intron one of RET gene are predominantly found in HSCR, which may cause a reduced c-RET expression in patient. In this study, a HSCR patient carrying a risk allele T in rs2435362 ...postprin

Intra-hepatic arterial pseudoaneurysm causing life-threatening upper gastrointestinal bleed after removal of biliary drainage catheter

Hepatic artery pseudoaneurysms are an uncommon complication of percutaneous biliary drainage catheter insertion. The authors report a case of a hepatic artery pseudoaneurysm following percutaneous internal-external biliary drain insertion. This led to massive haemobilia when the catheter was removed and presented clinically as life-threatening upper gastrointestinal bleed. The clinical and imaging manifestations are discussed along with the management of the patient

Clinical Characteristics and Transmission of COVID-19 in Children and Youths During 3 Waves of Outbreaks in Hong Kong

IMPORTANCE: Schools were closed intermittently across Hong Kong to control the COVID-19 outbreak, which led to significant physical and psychosocial problems among children and youths. OBJECTIVE: To compare the clinical characteristics and sources of infection among children and youths with COVID-19 during the 3 waves of outbreaks in Hong Kong in 2020. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study involved children and youths aged 18 years or younger with COVID-19 in the 3 waves of outbreaks from January 23 through December 2, 2020. Data were analyzed from December 2020 through January 2021. MAIN OUTCOMES AND MEASURES: Demographic characteristics, travel and contact histories, lengths of hospital stay, and symptoms were captured through the central electronic database. Individuals who were infected without recent international travel were defined as having domestic infections. RESULTS: Among 397 children and youths confirmed with COVID-19 infections, the mean (SD) age was 9.95 (5.34) years, 220 individuals (55.4%) were male, and 154 individuals (38.8%) were asymptomatic. There were significantly more individuals who were infected without symptoms in the second wave (59 of 118 individuals [50.0%]) and third wave (94 of 265 individuals [35.5%]) than in the first wave (1 of 14 individuals [7.1%]) (P = .001). Significantly fewer individuals who were infected in the second and third waves, compared with the first wave, had fever (first wave: 10 individuals [71.4%]; second wave: 22 individuals [18.5%]; third wave: 98 individuals [37.0%]; P < .001) or cough (first wave: 6 individuals [42.9%]; second wave: 15 individuals [12.7%]; third wave: 52 individuals [19.6%]; P = .02). Among all individuals, 394 individuals (99.2%) had mild illness. One patient developed chilblains (ie, COVID toes), 1 patient developed multisystem inflammatory syndrome in children, and 1 patient developed post–COVID-19 autoimmune hemolytic anemia. In all 3 waves, 204 patients with COVID-19 (51.4%) had domestic infections. Among these individuals, 186 (91.2%) reported having a contact history with another individual with COVID-19, of which most (183 individuals [90.0%]) were family members. In the third wave, 18 individuals with domestic infections had unknown contact histories. Three schoolmates were confirmed with COVID-19 on the same day and were reported to be close contacts. CONCLUSIONS AND RELEVANCE: his cross-sectional study found that nearly all children and youths with COVID-19 in Hong Kong had mild illness. These findings suggest that household transmission was the main source of infection for children and youths with domestic infections and that the risk of being infected at school was small

COVID-19 In Children Across Three Asian Cosmopolitan Regions

As another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p < 0.001, respectively) and had more imported cases (87.5% vs. 16.5% vs. 0%, p < 0.001, respectively). The imported cases were also older (13.4 vs. 7.6 years, p < 0.001). More cases in HKSAR were asymptomatic compared to Korea and Wuhan (45.5% vs. 22.0% vs. 20.9%, p < 0.001, respectively), and significantly more patients from Wuhan developed fever (40.6% vs. 29.7% vs. 21.6%, p=0.003, respectively). There were significantly less imported cases than domestic cases developing fever after adjusting for age and region of origin (p = 0.046). 5.4% to 10.8% of patients reported anosmia and ageusia. None developed pediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PMIS-TS). In general, adolescents were more likely to be asymptomatic and less likely to develop fever, but required longer hospital stays. In conclusion, majority patients in this pediatric Asian cohort had a mild disease. None developed PIMS-TS. Their clinical characteristics were influenced by travel history and age

Vitamin B₁₂ and folate decrease inflammation and fibrosis in NASH by preventing syntaxin 17 homocysteinylation

Background & Aims Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B12 (B12) and folate levels are negative correlated, with non-alcoholic steatohepatitis (NASH) severity. However, it is not known whether hyperhomocysteinemia (HHcy) plays a pathogenic role in NASH. Methods We examined the effects of HHcy on NASH progression, metabolism, and autophagy in dietary and genetic mouse models, patients, and primates. We employed vitamin B12 (B12) and folate (Fol) to reverse NASH features in mice and cell culture. Results Serum Hcy correlated with hepatic inflammation and fibrosis in NASH. Elevated hepatic Hcy induced and exacerbated NASH. Gene expression of hepatic Hcy-metabolizing enzymes was downregulated in NASH. Surprisingly, we found increased homocysteinylation (Hcy-lation) and ubiquitination of multiple hepatic proteins in NASH including the key autophagosome/lysosome fusion protein, Syntaxin 17 (Stx17). This protein was Hcy-lated and ubiquitinated, and its degradation led to a block in autophagy. Genetic manipulation of Stx17 revealed its critical role in regulating autophagy, inflammation and fibrosis during HHcy. Remarkably, dietary B12/Fol, which promotes enzymatic conversion of Hcy to methionine, decreased HHcy and hepatic Hcy-lated protein levels, restored Stx17 expression and autophagy, stimulated β -oxidation of fatty acids, and improved hepatic histology in mice with pre-established NASH. Conclusions HHcy plays a key role in the pathogenesis of NASH via Stx17 homocysteinylation. B12/folate also may represent a novel first-line therapy for NASH. Lay summary The incidence of non-alcoholic steatohepatitis, for which there are no approved pharmacological therapies, is increasing, posing a significant healthcare challenge. Herein, based on studies in mice, primates and humans, we found that dietary supplementation with vitamin B12 and folate could have therapeutic potential for the prevention or treatment of non-alcoholic steatohepatitis

Neural crest and Hirschsprung’s disease

Neural crest cells are a transient population of stem cells in vertebrates that give rise to the entire peripheral nervous system (PNS) as well as various non-neural progenies. A peculiar control and coordination of proliferation, migration and differentiation is required for neural crest cells to generate a full diversity of progenies, navigate different organs and establish functional domains in their target organs. Defects in such developmental process may lead to a board spectrum of congenital disorders, and in some cases, also cancer. In this review, we will focus on one specific neurocristopathy in the PNS: the Hirschsprung’s disease (colonic aganglionosis), to emphasize how unraveling the molecular mechanisms underlying the neural crest cell fate determination and progression may facilitate our understanding of the disease etiologies and future development of therapies

Electrogastrographic changes in children who undergo day-surgery anesthesia

Background/Purpose: Postoperative Nausea And Vomiting Is Common After General Anesthesia. The Timing Of Resuming Oral Input Is Arbitrary. This Study Aims To Estimate The Duration Of Emetic Effects Of General Anesthesia After Day Surgery In Children With Electrogastrography (Egg). Methods. Children Between The Age Of 3 And 12 Years Undergoing Elective Nonabdominal Surgery Were Recruited. The Standard Anesthesia Protocol Of Thiopentone (5 Mg/Kg), O2 (30%), N2o (70%), And Isoflurane (1.5%) Was Adopted Caudal Block Was Applied To The Patients. A Laryngeal Mask Was Used A Mobile Electrogastrogram (Egg) Machine (Synectic; International Medtronic Synectics, Stockholm, Sweden) Was Attached To The Epigastrium Of The Patient At Least 1 Hour Before The Operation And The Recording Continued Through The Operation And For A Further 2 Hours After The Operation. The First Half Hour Of Preoperative Recording Was Taken As Normal Control Period. The Results Were Analyzed Using Paired T Test Results: Twenty Patients Who Underwent Circumcision Under General Anesthesia Were Studied The Mean Age Was 6.6 Years. The Mean Anesthetic Duration Was 33.2 Min. The Tachygastria Component (Associated With Nausea And Vomiting) Became Prominent Immediately After Reduction And Returned To Normal 1 Half Hour After Cessation Of General Anesthesia. The Dominant Frequency Instability Coefficient Of Egg (Dfic) And The Dominant Power Instability Coefficient (Dpic) Peaked During The First Half Hour Period Postoperatively And Returned To Baseline 1 Hour Postoperatively (Dpic, P > .05). Bradygastria Became Prominent During The Periods 1 Half-Hour Before And 1 Half-Hour After The General Anesthesia And Returned To Baseline 1 Hour Postoperatively (P < .05). Conclusions: Significant Egg Changes Occur During Day-Surgery General Anesthesia For Children Undergoing Nonabdominal Surgery. These Changes Return To Baseline 1 Hour After Reversal Of Anesthesia. It Is Probably Safe To Restart Feeding 1 Hour Later After Day-Surgery General Anesthesia Without Causing Nausea And Vomiting.link_to_subscribed_fulltex