bluuebunny/crossref_metadata_2025_split huggingface dataset:
A215 MDR3 DEFICIENCY MIMICKING WILSON DISEASE
Authors: Flanagan M , Little R , Siddiqui I , Jones N , Ng V 
Published: March 2021

Abstract

Background
The chronic phenotype of ALF includes a broad differential diagnosis. Class III multi-drug resistance P-glycoprotein 3 (MDR3) deficiency, also referred to as progressive familial intrahepatic cholestasis type 3, is an autosomal recessive genetic disorder. It is caused by a defect on the ABCB4 gene located on chromosome 7, which encodes MDR3. MDR3 is responsible for transporting phosphatidylcholine across the canalicular membrane, thereby allowing it to be incorporated into bile micelles. MDR3 deficiency results in increased levels of free bile acids and detergent bile. Progressive cholangiopathy ensues from this detergent bile and indirectly leads to cholestasis and liver failure in severe cases. Significantly increased urinary and hepatic copper (Cu), which are hallmarks of Wilson disease, have also been reported in patients with acute hepatitis and cholestasis including patients with MDR3 deficiency

Aims
We report a case of a girl who presented with a chronic phenotype of PALF, who had multiple features of Wilson disease and so was treated as such until genetic analysis confirmed MDR3 deficiency
Methods

Results
A 6 year old girl presented to the ED with a 1mth history of epistaxis and a 1wk history of abdominal pain and distension, facial edema, pallor and fever. Her family history was significant for parental consanguinity and maternal itch during pregnancy. On examination she had clubbing, scleral icterus and a distended abdomen with hepatosplenomegaly. Her bloodwork showed bicytopenia (HGB 53 & Plts 63) along with liver dysfunction (INR 2.9, albumin 25, conjugated bilirubin 9) and raised liver enzymes (transaminases & GGT &gt;10xULN). Her total serum bile acids were raised at 134. An US showed hepatosplenomegaly with multiple hyperechoic nodules and perisplenic varices. She was extensively worked up for malignancy, autoimmune and metabolic disease. Serum ceruloplasmin was reduced, ophthalmology examination showed no KF rings and her 24hr urinary Cu was 10xULN. Liver Cu quantification was markedly raised at 40xULN. Liver biopsy showed cirrhosis with fibrosis related minimal non-specific portal and septal inflammation. Additionally, complete loss of canalicular staining on immunohistochemistry for MDR3 protein was noted, suggestive of MDR3 deficiency. Based on the Cu levels, a provisional diagnosis of Wilson disease was made and Cu chelation therapy was commenced pending genetic testing. A cholestatic gene panel subsequently showed homozygous pathogenic variant for the ABCB4 gene. Trientine was stopped and she was commenced on ursodeoxycholic acid. Though biochemically she remains largely unchanged, she is clinically stable whilst awaiting a liver transplant

Conclusions
This case highlights the diagnostic difficulties associated with Cu test result interpretation in patients with chronic cholestatic liver disease and urges a thorough consideration of alternative diagnoses of PALF

Funding Agencies
None
A216 CLINICAL MANIFESTATIONS OF LYSOSOMAL ACID LIPASE DEFICIENCY (LAL-D): THE INTERNATIONAL LAL-D REGISTRY
Authors: Francis M , Balwani M , Balistreri W , D’Antiga L , Fang S , Jones S , Ros E , Abel F , Wilson D 
Published: March 2021

Abstract

Background
Lysosomal acid lipase deficiency (LAL-D) is a rare, autosomal recessive disease caused by pathogenic variants in the LIPA gene. Lysosomal accumulation of cholesteryl esters and triglycerides leads to cirrhosis and dyslipidemia across a clinical spectrum, and affect both infants and children/adults.

Aims
An international registry (NCT01633489; Alexion Pharmaceuticals, Inc.; 2013–ongoing) was established to better understand the natural history of lysosomal acid lipase deficiency (LAL-D) and to evaluate long-term treatment outcomes.

Methods
Baseline findings for patients enrolled through July 1, 2019 are presented. Of 190 patients enrolled, 35 were excluded from this analysis (LIPA carrier, deceased at enrollment, unconfirmed LAL-D diagnosis); 155 patients with confirmed LAL-D diagnosis were included (12 infants, 143 children/adults). LAL enzyme activity analysis was performed for 145/154 patients (94%) and genetic testing for 128/154 patients (83%).

Results
Of 105 children/adults with reported LIPA mutations, 39 were homozygous and 34 were compound heterozygous for the common LIPA mutation E8SJM (c.894G&gt;A); 6 infants with reported LIPA mutations were homozygotes and 2 were compound heterozygotes. Of the 155 patients, 62% were &lt;18 years, 52% were male, and 85% were white. Median (range) age at clinical onset was 0.2 years (0.0–0.7) among infants and 6.0 years (0.0–41.3) among 133 children/adults with data; median (range) age at diagnosis was 0.2 years (−0.1 to 1.2) among infants and 10.8 years (0.2–53.6) among 135 children/adults with data. Manifestations that raised suspicion of LAL-D were reported in 149/155 patients. Infants (12 with data) presented predominantly with hepatomegaly (75%), splenomegaly (58%), nausea/vomiting (58%), and diarrhea (50%), and 50% had a known family history of LAL-D. Children/adults (n=143) presented predominantly with elevated alanine aminotransferase levels (67%), hepatomegaly (66%), and elevated aspartate aminotransferase levels (65%). Of 74 children/adults with baseline liver biopsy, 58% had microvesicular steatosis, 16% had micro- and macrovesicular steatosis, and 32% had lobular inflammation. Of the 155 patients, 6% had a medical history of cirrhosis. Analyses exploring the genotype-phenotype relationship will be presented.

Conclusions
Registry data of &gt;150 LAL-D patients demonstrate early symptom onset, variable clinical manifestations, and a significant diagnostic delay in children/adults.

Funding Agencies
Alexion Pharmaceuticals, Inc.
A229 PROMOTION OF COLONIC ANASTOMOTIC HEALING WITH PERIOPERATIVE SUPPLEMENTATION WITH OLIGOSACCHARIDES
Authors: Hajjar R , Oliero M , Cuisiniere T , Fragoso G , Calve A , Djediai S , Annabi B , Richard C , Santos M M 
Published: March 2021

Abstract

Background
Colorectal resection is a standard procedure in the management of colorectal cancer (CRC) and inflammatory bowel disease. Anastomotic leak (AL) is a major complication in colorectal resections, and the gut microbiota may play a role in the healing and development of AL. Short-chain fatty acids (SCFAs), namely butyrate, have been involved in anastomotic healing when administered into the bowel via enema. Due to the mechanical stress associated with enemas after the confection of a fresh and fragile anastomosis, other butyrate-increasing strategies are required.

Aims
To promote anastomotic healing and prevent AL by using inulin and galacto-oligosaccharides (GOS) supplementation to modulate the microbiota toward a butyrate-producing profile.

Methods
Mice were fed diets supplemented with inulin, GOS or cellulose, as a non-fermentable control, for two weeks and underwent a proximal colonic anastomosis under general anesthesia. Healing of the anastomosis, both macroscopically and microscopically, was assessed six days after surgery. Epithelial proliferation, mucus production and integrity of the gut barrier were assessed.

Results
Inulin and GOS supplementation increased SCFAs in the colon and were associated with better postoperative weight recovery and macroscopic anastomotic healing. Microscopically, mucosal continuity was promoted by inulin and GOS. Mucus production was found to be similar in all groups. The gut barrier was found to be improved with inulin and GOS as shown by less bacterial translocation.

Conclusions
Inulin and GOS may prevent AL and promote anastomotic healing. This effect appears to be mediated by improved mucosal proliferation.

Funding Agencies
CIHRNatural Sciences and Engineering Research Council of Canada; Institut du cancer de Montréal; Fonds de recherche du Québec en santé
A230 ISOMALTODEXTRIN DOSE-DEPENDENTLY REDUCES COLITIS DEVELOPMENT IN HLA-B27 RAT COLITIS MODEL WITH ASSOCIATED CHANGES TO GUT MICROBIOME COMPOSITION AND SHORT CHAIN FATTY ACID PRODUCTION
Authors: Premraj N , Valcheva R , Dieleman L A 
Published: March 2021

Abstract

Background
Inflammatory bowel disease (IBD) is characterized by altered intestinal microbiome (i.e. dysbiosis), described by reduced strict butyrate-producing anaerobes versus increased facultative anaerobes. Data from preclinical studies and clinical trials show prebiotic inulin-type fibers can prevent and reduce colitis. However, other dietary fibers (e.g. resistant starches, RS) are understudied and it is unknown if RS-induced microbial shifts are protective in experimental colitis.

Aims
Assess efficacy of isomaltodextrin (IMD), a novel RS, to reduce intestinal inflammation in HLA-B27 transgenic (TG) rat colitis model and identify protective mechanisms associated with gut microbial composition and function.

Methods
4 week old HLA-B27 TG rats were fed standard chow supplemented with: 7.5% IMD (low dose, LD), 15% IMD (high dose, HD), negative control (15% cellulose, NC), or positive control (15% fructooligosaccharides, PC) for 12 weeks. Body weight and food intake were measured. Cecal and colonic inflammation assessed by weight/length ratio, macroscopic scoring and mucosal IL-1β secretion. Changes in microbial energy metabolism evaluated by measuring short chain fatty acid (SCFA) production in stool and cecal contents. Endpoint fecal and cecal microbiota composition differences assessed by 16S rRNA gene sequencing (Illumina MiSeq platform).

Results
IMD showed dose-dependent effect on cecal inflammation, measured by macroscopic tissue scoring, weight/length ratio and IL-1β secretion. HD rats had significantly lower cecum IL-1β concentration compared to NC (q=0.01), while LD showed only a trend (q=0.09). HD had significantly higher cecal amounts of Bacteroidaceae and Allobaculum spp. and lower amounts of Peptostreptococcaceae, Eubacterium and Barnesiella spp. versus the LD and NC. HD was associated with significantly higher total SCFA compared to NC (q&lt;0.01) and showed a trend of higher total SCFA than LD (q=0.06). Analysis of SCFAs revealed propionate, isobutyrate and valerate ratios were significantly lower in HD than LD and NC. HD showed a trend of higher ratio of butyrate + acetate compared to NC. This suggests increased carbohydrate fermentation by acetate-producing and -converting microbial groups. Correlation analysis confirmed IL-1β concentrations were positively associated with isobutyrate (r=0.52, q&lt;0.01), valerate (r=0.54, q&lt;0.01), and propionate (r=0.48, q&lt;0.01), suggesting their use as chronic inflammation markers in HLA-B27 models.

Conclusions
IMD was dose-dependently effective in reducing chronic cecal inflammation in experimental colitis. Benefits were associated with specific shifts in gut microbiome composition and SCFA production. Results from this preclinical study warrant future microbiota-altering intervention trials using IMD in clinical IBD.

Funding Agencies
Hayashibara Co., Ltd.
A234 EVALUATING THE EFFECT OF STOOL SUPERNATANTS FROM IBS PATIENTS AND HEALTHY CONTROLS ON THE EXCITABILITY OF DRG NEURONS
Authors: Neary E , Jiménez-Vargas N N , Osman S , Reed D E , Vanner S , Lomax A E 
Published: March 2021

Abstract

Background
Abdominal pain is commonly described in chronic disorders such as irritable bowel syndrome (IBS), but the underlying mechanisms are currently unclear. The stool metabolomic and microbiota profiles of IBS and healthy patients have shown distinct differences. Additionally, IBS stool supernatants have previously been demonstrated to induce hypersensitivity of nociceptive nerves in the ex vivo mouse colon, suggesting that mediators in the stool can sensitize nociceptors. However, the effects of healthy control (HC) or IBS patient stool supernatants on the excitability of DRG neurons have not been clarified.

Aims
To evaluate the effect of HC and IBS supernatant on DRG neurons.

Methods
HC (n=8 patients) or IBS (n=10 patients) stool was collected, dissolved and homogenized with bicarbonate-buffered Krebs solution at 37°C in a 1/10 dilution. DRG neurons from C57BL/6 mice were dissociated and incubated overnight with HC or IBS supernatant in a Krebs dissolution. Changes in DRG neuronal excitability were recorded using perforated patch-clamp techniques to measure the rheobase (amount of current needed to elicit an action potential). The effect of the IBS and HC stool supernatants on the resting membrane potential (RMP) was also recorded.

Results
Overnight incubations with supernatant of HC stool diluted in Krebs solution (n=28 neurons) did not significantly decrease the rheobase compared to control neurons (n=22) (62.7 ± 3.9 pA vs 64.2 ± 2.7 pA). In a parallel experiment, we evaluated the effect of IBS stool supernatants diluted in Krebs (n=52 neurons) and found that they significantly decreased the rheobase compared to the supernatant of HC diluted in Krebs and control neurons (52.3 ± 2.3; p&lt;0.05). The data were analyzed with a one-way ANOVA and Tukey’s test. Incubations with IBS supernatant decreased the RMP compared to HC supernatant (-42.6 ± 0.6 mV vs. -46.0 ± 0.9 mV; p&lt;0.01), which was calculated with an unpaired t-test.

Conclusions
These findings suggest that mediators in IBS stool increase the excitability of DRG neurons compared to HC stool supernatant, and thus may contribute to pain signaling in IBS patients.

Funding Agencies
CIHR
A242 THE AIR BETWEEN US: A CASE OF PSEUDOCYST PERFORATION POST-ENDOSCOPIC CLIPPING OF A BLEEDING PANCREATIC-COLONIC FISTULA
Authors: Sedarous M , Balubaid I , Basden A , Rahman A 
Published: March 2021

Abstract

Background
Pancreatic fistula is an uncommon complication of pancreatitis and is associated with increased morbidity. We discuss a case of pancreatic-colonic fistulization followed by the first reported case of pseudocyst perforation post-colonoscopy.

Aims
Case

Methods
A 51 year-old female with decompensated alcoholic cirrhosis admitted with hepatic encephalopathy developed large volume hematochezia during admission. Past medical history includes pancreatic pseudocyst, GERD and remote hernia repairs. For the hematochezia, she was investigated with an EGD and colonoscopy. In the distal descending colon, a bleeding lesion was identified and treated with clips and epinephrine injection (Figures 1 and 2). Five hours post-procedure, she developed abdominal distention. CT abdomen pelvis revealed large volume of free air and simple fluid within the abdominal cavity likely secondary to rupture pseudocyst rupture. The previously visualized pseudocyst was filled with gas plastered against the descending colon. She remained medically stable with conservative management.

Results
Discussion

Conclusions
Pancreatic-colonic fistula is an uncommon but potentially life-threatening complication of acute pancreatitis associated with high risk of complications. They are found in 4% of admitted inpatients with acute pancreatitis. There are three proposed mechanisms for their development: firstly, inflammation and activated pancreatic lytic enzymes; secondly, pressure necrosis from a contiguous mass; thirdly, localized portal hypertension. Classically, pancreatic-colonic fistulas present with diarrhea, fever and hematochezia. Gastrointestinal bleeding occurs in 60% of cases. The source of bleed has been described to be originating most commonly from the splenic artery and to a lesser extent, the margin of the fistula or, rarely, erosion of splenic parenchyma. Reported therapeutic management strategies include: hemoclippings and Greenplast sprayings, endoscopic pancreatic stent, transgastric nasocystic drainage catheter placements, injection of N-butyl-2-cyanocrylate and transpapillary nasopancreatic drainage.
Pseudocysts arise in 25% of patients with chronic pancreatitis. Pseudocysts may regress through a variety of mechanisms: spontaneously after inflammation from pancreatitis resolves, natural drainage through the pancreatic duct into the duodenum, or through a complicating fistulous tract connecting to the gastrointestinal tract. Rarely, the pseudocyst can resolve as it leaks or perforates into the abdominal cavity. Pancreatic pseudocysts may perforate spontaneously into the free peritoneal cavity, stomach, duodenum, colon, portal vein, pleural cavity, or through the abdominal wall. We report the first case, to our knowledge, of pancreatic pseudocyst perforation post-clipping of bleeding pancreatic-colonic fistula.

Funding Agencies
None
A243 A RETROSPECTIVE REVIEW OF THE RADIOGRAPHIC DIAGNOSIS AND SURGICAL RESECTION RATES OF PANCREATIC SEROUS CYSTS
Authors: Monachese M , Li S , Salim M , Guimaraes L , James P D 
Published: March 2021

Abstract

Background
Pancreatic cystic lesions are increasingly identified in persons undergoing abdominal imaging. Serous cystic neoplasms (SCNs) have a very low risk of malignant transformation. Resection of SCNs is not recommended in the absence of related symptoms. The accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) to identify SCNs is not known and may impact clinical care.

Aims
To evaluate the accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) for the diagnosis of SCN. To see how this can impact the decision to resect suspected SCNs.

Methods
Retrospective cohort study of patients from the University Health Network with suspected SCNs from 2017–2020 who underwent either a CT or MRI of the abdomen. Reports noting pancreatic cystic lesions were identified and reviewed. Only cases with suspected SCNs were included. Clinical (age, sex, symptoms, treatment) and radiographic (type of imaging, reported cyst characteristics) data was collected. Pathology was reviewed for all cases where the cysts was biopsied or resected during follow-up. The gold standard for the diagnosis for SCN was pathology of resected specimen or EUS-guided biopsy cytopathology showing no evidence of a mucinous lesion, CEA level below 10ug per L and amylase level below 50 U/L.

Results
163 patients were included in the study. 99 (61%) were female and 98 (60%) underwent CT scan. EUS-guided biopsy was performed in 24 (15%) of patients and 8 (5%) had surgical resection. Multidisciplinary review was performed in 6 of the 8 cases that went to surgery. Of the resected specimens, 5 (63%) were SCN, 1 was a mucinous cystic lesion, 1 was a neuroendocrine tumor and 1 was a carcinoma. Two patients underwent EUS evaluation prior to surgical resection. In one case SCN was resected when EUS reported an undetermined cyst type. Reasons for surgical resection were: the diagnosis of serous cyst was not definitive (n=5), symptoms (n=2), and high-risk mucinous cystic neoplasm identified on EUS (n=1). Of 30 patients with pathology available, 15 (50%) were confirmed to have a SCN. CT and MRI had a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 25%, 52% and 80%, respectively.

Conclusions
Surgical resection for SCN lesions is driven by diagnostic uncertainty after cross-sectional imaging. Multidisciplinary review and EUS evaluation may improve diagnostic accuracy and should be considered prior to surgical resection of possible SCN lesions.

Funding Agencies
None
Subterranean Termite (Coptotermes gestroi(Blattodea: Rhinotermitidae)) Colony Elimination Through Exposure to a Novaluron CSI Bait Formulation in Laboratory
Authors: Chouvenc Thomas 
Published: March 2021

AbstractThe development of baits for subterranean termite control over the past 25 yr has provided cost-effective alternatives to liquid termiticide treatments. Current bait products use one of the few available benzoylurea chitin synthesis inhibitors (CSIs) labeled for subterranean termites. These insecticides are used because of their nonrepellency, their slow-acting mode of action, and their dose-independent lethal time. Although many studies have provided ample evidence of the efficacy of CSI baits for subterranean termite colony elimination, most have focused on hexaflumuron and noviflumuron. However, bait products using alternative CSIs have not received the same level of scrutiny, limiting the amount of evidence proving their efficacy. One such compound is novaluron, the active ingredient currently used in the Trelona ATBS—Advance Termite Baiting System bait product. The current study independently tested the efficacy of this commercially available bait formulation against whole colonies of Coptotermes gestroi (Wamann) (~63,910 workers) in the laboratory, using an extended experimental setup to simulate a 15-m foraging distance from the central part of the nest to the bait, while having access to alternative food sources. Treated colonies progressively ceased to feed on wood items within 45 d after being provided access to the novaluron bait formulation, with a subsequent progressive collapse of the population, leading to colony elimination by 91 d. This study therefore confirms the efficacy of novaluron baits against subterranean termites, and currently remains one of the few CSIs that can be applied for the successful control of Coptotermes infestations.
Identification and Characterization of Aminopeptidase N 1 Gene of the Indian Malaria Vector Anopheles culicifacies (Diptera: Culicidae)
Authors: Jakhar Renu , Gakhar Surendra Kumar 
Published: March 2021

Abstract
Aminopeptidase N1 (APN) is one of the important enzymes involved in blood digestion and is up-regulated along with several other enzymes in response to bloodmeal ingestion. APN is a zinc metalloprotease that cleaves one amino acid residue at a time from the amino terminus of the protein. The APN1 gene of the Indian malaria vector Anopheles culicifacies Giles was cloned and characterized. The An. culicifacies APN1 (AcAPN1) gene has an Open Reading Frame of 3084 basepairs which encodes a putative protein of 1027 amino acids. The coding region of the gene shares 81% and 78% similarity to the APN1 genes found in An. stephensi (Diptera: Culicidae) and An. gambiae (Diptera: Culicidae), respectively. The organization of the APN1 gene was studied in available mosquito genomes and a three-dimensional structure of AcAPN1 modeled using homology structure modeling. The enzymatic active site was predicted to consist of HEYAH and GAMEN amino acid residues, and a comparison of the protein sequences among different genera revealed the conservation of zinc-binding residues. The expression pattern of AcAPN1 showed that the gene was expressed rapidly in response to the ingestion of the bloodmeal and therefore this gene may be used to exploit its promoter region as an antiparasite candidate molecule.
Does It Pay to Conduct Midrotation Competition Control and/or Fertilization? Results from Two Thinned Loblolly Pine Studies in the Coastal Plain of Georgia
Authors: Li Yanshu , Dickens E David , Sault Matthew , Siry Jacek P , Izlar Robert L , Clabo David C , Tyson William G 
Published: March 2021

AbstractThe effects of midrotation competition control and fertilization were studied in two loblolly pine stands in the Coastal Plain of Georgia. The use of fertilizer or herbicide alone did not enhance wood yields above the control, which negates the cost spent to conduct these practices. The combined treatment of fertilization and herbicide promoted higher average pine annual increment and greater proportion of sawtimber. Site limiting factors, most likely both competing woody vegetation and low nutrient status, largely determined the effectiveness and priority of midrotation treatments. The economic returns of the combined treatment varied considerably depending on stumpage prices, treatment costs, and magnitude and duration of the growth response. Sawtimber prices (absolute value and relative to pulpwood and chip-n-saw) play a critical role in the marginal returns of midrotation treatments. Continued depressed sawtimber prices will discourage private landowners from investing in midrotation vegetation control and fertilization.