Gastrointestinal Abnormalities Research Articles

Analysis of imaging in pediatric bronchopulmonary foregut malformations with literature review: case reports

BackgroundBronchopulmonary foregut malformation (BPFM) is an uncommon condition, with few case reports documented in both national and international literature. This scarcity underscores the importance of utilizing effective imaging techniques to improve our understanding and diagnostic precision concerning this disorder.Case descriptionIn the first case report, a neonate, born at full term and aged 15 days, presented with symptoms including dyspnea, coughing, wheezing, cyanosis, and vomiting. Initial diagnostic evaluations, which included chest radiography and upper gastrointestinal tract radiography, led to an erroneous initial diagnosis of a left-sided diaphragmatic hernia, accompanied by a suspicion of infection. In the second case report, another neonate, also born at full term but aged 5 days, exhibited symptoms such as coughing, choking, and mild vomiting. Utilizing a combination of computed tomography (CT) scans (plain, enhanced, and reconstructed), chest x-ray, and upper gastrointestinal tract radiography, the diagnosis of BPFM was accurately determined.ConclusionComprehensive imaging examinations play a crucial role in reducing misdiagnosis and diagnostic oversights in cases of BPFM. Given its rarity, BPFM often manifests as a sequestered lung accompanied by gastrointestinal abnormalities. Hence, the integration of CT scans with gastrointestinal tract radiography can substantially improve diagnostic precision in such cases.

A Robust Approach for Ulcer Classification/Detection in WCE Images

Wireless Capsule Endoscopy (WCE) is a medical diagnostic technique recognized for its minimally invasive and painless nature for the patients. It uses remote imaging techniques to explore various segments of the gastrointestinal (GI) tract, particularly the hard-to-reach small intestine, making it an effective alternative to traditional endoscopic techniques. However, physicians face a significant challenge when it comes to analyzing a large number of endoscopic images due to the effort and time required. It is therefore imperative to implement aided-diagnostic systems capable of automatically detecting suspicious areas for subsequent medical assessment. In this paper, we present a novel approach to identify gastrointestinal tract abnormalities from WCE images, with a particular focus on ulcerated areas. Our approach involves the use of the Median Robust Extended Local Binary Pattern (MRELBP) descriptor, which effectively overcomes the challenges faced when WCE image acquisition, such as variations in illumination and contrast, rotation, and noise. Using machine learning algorithms, we conducted experiments on the extensive Kvasir-Capsule dataset, and subsequently compared our results with recent relevant studies. Noteworthy is the fact that our approach achieved an accuracy of 97.04% with the SVM (RBF) classifier and 96.77% with the RF classifier.

Gastrointestinal bleeding risk factors in type A aortic dissection post-aortic arch replacement.

Gastrointestinal bleeding (GIB) is a notable complication in patients diagnosed with aortic dissection (AD). We evaluated the outcomes and identified the risk factors associated with GIB in patients with AD. A retrospective case-control study was conducted on patients diagnosed with type A aortic dissection (TAAD) who underwent total aortic arch replacement (TAAR) at our institution from July 2021 to July 2023. Comprehensive clinical data, laboratory findings, and imaging results were meticulously gathered and analyzed to identify potential risk factors linked to GIB in this patient cohort. Of the 198 AD patients who underwent TAAR, 38 (19.2%) developed postoperative GIB (GIB group), with a median interval of 7 days between surgery and bleeding onset. The GIB group exhibited significantly higher mortality (26.3% vs. 3.1%, P<0.001), prolonged intensive care unit (ICU) stay {15 [interquartile range (IQR), 8-25] vs. 7 (IQR, 5-12) days, P<0.001}, and extended duration of ventilation [168 (IQR, 120-372) vs. 71 (IQR, 34-148) hours, P<0.001] compared to the control group (n=160, 80.8%). Logistic regression analysis identified age >54 years [odds ratio (OR): 3.529], intraoperative red blood cell (RBC) transfusion >600 mL (OR: 3.865), and concomitant celiac trunk and superior mesenteric artery (SMA) hypoperfusion (OR: 15.974) as independent risk factors for GIB in AD patients. GIB subsequent to TAAR in AD patients is linked to adverse prognosis. Factors such as advanced age, extensive intraoperative transfusion, and gastrointestinal (GI) perfusion abnormalities may heighten the risk of GIB in this patient population.

Hypoxia-inducible factor 1α inhibits heat stress-induced pig intestinal epithelial cell apoptosis through eif2α/ATF4/CHOP signaling

Unstoppable global warming and increased frequency of extreme heat leads to human and animals easier to suffer from heat stress (HS), with gastrointestinal abnormalities as one of the initial clinical symptoms. HS induces intestinal mucosal damage owing to intestinal hypoxia and hyperthermia. Hypoxia-inducible factor 1α (HIF-1α) activates numerous genes to mediate cell hypoxic responses; however, its role in HS-treated intestinal mucosa is unknown. This work aimed to explore HIF-1α function and regulatory mechanisms in HS-treated pig intestines. We assigned 10 pigs to control and moderate HS groups. Physical signs, stress, and antioxidant levels were detected, and the intestines were harvested after 72 h of HS treatment to study histological changes and HIF-1α, heat shock protein 90 (HSP90), and prolyl-4-hydroxylase 2 (PHD-2) expression. In addition, porcine intestinal columnar epithelial cells (IPEC-J2) underwent HS treatment (42 °C, 5 % O2) to further explore the functions and regulatory mechanism of HIF-1α. The results of histological examination revealed HS caused intestinal villi damage and increased apoptotic epithelial cell; the expression of HIF-1α and HSP90 increased while PHD-2 showed and opposite trend. Transcriptome sequencing analysis revealed that HS activated HIF-1 signaling. To further explore the role of HIF-1α on HS induced IPEC-J2 apoptosis, the HIF-1α was interfered and overexpression respectively, and the result confirmed that HIF-1α could inhibited cell apoptosis under HS. Furthermore, HS-induced apoptosis depends on eukaryotic initiation factor 2 alpha (eif2α)/activating transcription factor 4 (ATF4)/CCAAT-enhancer-binding protein homologous protein (CHOP) pathway, and HIF-1α can inhibit this pathway to alleviate IPEC-J2 cell apoptosis. In conclusion, this study suggests that HS can promote intestinal epithelial cell apoptosis and cause pig intestinal mucosal barrier damage; the HIF-1α can alleviate cell apoptosis by inhibiting eif2α/ATF4/CHOP signaling. These results indicate that HIF-1α plays a protective role in HS, and offers a potential target for HS prevention and mitigation.

Nutritional Support System (NSS) as a New Therapeutic Strategy for Cerebral Palsy.

Cerebral palsy (CP) is part of a group of nonprogressive motor disorders. The disease affects movement and posture and constitutes the most frequent cause of motor disability in childhood. CP is characterized by spasticity, reflecting lesions in the pyramidal pathway. Treatment is currently focused on physical rehabilitation, and the annual progression of the disease is 2-3%. About 60% of these patients present severe degrees of malnutrition associated with dysphagia, gastrointestinal abnormalities, malabsorption, increased metabolism, and depression. These alterations promote sarcopenia functional dependence and affect the quality of life and delay the evolution of motor skills. Currently, there is evidence that the supplementation of several nutrients, dietary correction, and probiotics can improve neurological response by stimulating neuroplasticity, neuroregeneration, neurogenesis, and myelination. This therapeutic strategy could shorten the response period to treatment and increase both gross and fine motor skills. The interaction of nutrients and functional foods integrating a Nutritional Support System (NSS) has shown greater efficiency in neurological stimulation than when nutrients are supplied separately. The most studied elements in the neurological response are glutamine, arginine, zinc, selenium, cholecalciferol, nicotinic acid, thiamine, pyridoxine, folate, cobalamin, Spirulina, omega-3 fatty acids, ascorbic acid, glycine, tryptophan, and probiotics. The NSS represents a therapeutic alternative that will restore neurological function in patients with spasticity and pyramidal pathway lesions, both characteristics of patients with CP.

Clinical and genetic analysis of trichohepatoneurodevelopmental syndrome caused by a CCDC47 variant

Trichohepatoneurodevelopmental syndrome is an extremely uncommon autosomal recessive disorder resulting from variants in the CCDC47 gene, which encodes a Ca2+-binding endoplasmic reticulum (ER) transmembrane protein. To date, only four patients with CCDC47 deficiency have been reported, all of them with homozygous truncating CCDC47 variants. For this study, a Chinese family was recruited, which included a patient diagnosed with trichohepatoneurodevelopmental syndrome. Whole exome sequencing (WES) identified the proband's novel homozygous CCDC47 variation (NM_020198: c.634C > T(p.Arg212*). The variant was confirmed to be segregating in the proband and her unaffected relatives through Sanger sequencing. The patient described exhibited a clinical phenotype similar to that of patients with the CCDC47 variant. Compared to reported cases with CCDC47 pathogenic variants, our patients showed a novel complication of hearing impairment. In addition, brain abnormalities, small feet, bilateral hip dislocation, hip dysplasia, overlapping toes, pectus excavatum, scoliosis and narrow chest were not observed in our patient. We also examined five different variations and their corresponding phenotypes from five patients, both in current and previous research. Although some clinical manifestations of trichohepatoneurodevelopmental syndrome were highly variable, the most common phenotypes observed in these patients include microcephaly, profound intellectual disability, severe global development delay, pronounced growth restriction, hypotonia, woolly hair, facial dysmorphism, respiratory and visual abnormalities, gastrointestinal abnormalities, liver dysfunction, pruritus, skeletal and limb abnormalities, congenital heart defects and immunodeficiency. The present report is the first of a Chinese infant with homozygous variant in the CCDC47 gene. We expanded the genetic and phenotypic spectrum associated with trichohepatoneurodevelopmental syndrome.

The Effects of Unconventional Feed Fermentation on Intestinal Oxidative Stress in Animals.

Unconventional feed, which is abundant in China, contains anti-nutritional factors and toxins; however, these can be greatly reduced with microbial fermentation, thus improving the nutrient content of the feed, enhancing animal appetites, and ultimately significantly improving the intestinal health and growth performance of animals. When oxidative stress occurs, fermented feed can effectively reduce the damage caused by stress to the gastrointestinal tract, accelerate the removal of gastrointestinal abnormalities, improve the ability to resist intestinal stress, and ensure the efficient production of animals. This review introduces the application of unconventional fermented feed in animal production, and expounds upon the function of unconventional fermented feed in animals with oxidative stress symptoms, so as to provide a theoretical reference for the development and application of unconventional fermented feed in antioxidative stress reduction.

Is COVID-19 Infection a Multiorganic Disease? Focus on Extrapulmonary Involvement of SARS-CoV-2.

First described in December 2019 in Wuhan (China), COVID-19 disease rapidly spread worldwide, constituting the biggest pandemic in the last 100 years. Even if SARS-CoV-2, the agent responsible for COVID-19, is mainly associated with pulmonary injury, evidence is growing that this virus can affect many organs, including the heart and vascular endothelial cells, and cause haemostasis, CNS, and kidney and gastrointestinal tract abnormalities that can impact in the disease course and prognosis. In fact, COVID-19 may affect almost all the organs. Hence, SARS-CoV-2 is essentially a systemic infection that can present a large number of clinical manifestations, and it is variable in distribution and severity, which means it is potentially life-threatening. The goal of this comprehensive review paper in the series is to give an overview of non-pulmonary involvement in COVID-19, with a special focus on underlying pathophysiological mechanisms and clinical presentation.

P507 Can systematic upper gastrointestinal endoscopy benefit patients with Inflammatory Bowel Disease?

Abstract Background In the context of Inflammatory Bowel Disease (IBD), a comprehensive understanding of disease extent and related complications is essential for effective clinical care. While Crohn’s disease (CD) can affect the digestive tract from mouth to anus, ulcerative colitis (UC) is limited to the rectum and colon. This study investigates the potential utility of systemic gastroscopy in IBD management. Methods We conducted a retrospective cohort study using data from our gastroenterology department. Patients diagnosed with IBD who underwent systematic upper gastro-intestinal endoscopy (UGE) were included. Clinical, endoscopic, and histopathological data were gathered and analyzed. Results 141 CD and 61 UC patients were included. The mean age was 40,7 years, and the female to male ratio was 1,33. 95.5% of these patients had no upper gastrointestinal symptoms prior to undergoing UGE. Among the symptomatic participants, the most frequent complaints were dyspepsia and pyrosis. In 73.9% of asymptomatic patients, UGE showed a normal mucosa, the abnormalities found in these patients were: non-specific gastro-duodenal erosions and ulcerations (8.5% of cases), mild esophagitis (4% of cases), aphthoid ulcerations (2% of cases) and duodenal stenosis (0.5% of cases). In symptomatic participants, UGE was normal in 4 cases, it showed atrophy of the fundus mucosa in 1 case, esophageal hernia in 2 cases, and esophageal aphthoid ulcerations in 1 case. Gastro-duodenal biopsies were consistently undertaken, among asymptomatic patients, histopathological abnormalities included: lymphoplasmacytic Infiltrate (47,7%) and helicobacter pylori (HP)(38,1 %), nonspecific duodenitis (44,7%), gastric metaplasia, focal gastritis, atrophic villi and crypt hyperplasia were objectified in 3,5%, 3%, 1,5% and 0,5% of cases. Granulomas were noted in only 1% of cases, and Cryptitis and crypt abscess in 0,5%. In symptomatic participants, histologic abnormalities included metaplasia in the fundus (0.5%), lymphoplasmacytic infiltrate (2.5%), HP (2,4%), atrophic villi in the duodenum (0.5%) and glandular atrophy (0.5%). Our analysis did not reveal any significant associations between endoscopic lesions and UC (p=0.36) or CD (p=0.09) nor the presence of symptoms (p=0.08), however, a significant association was identified between male gender and the presence of endoscopic lesions (p=0.033). Conclusion Although IBD patients might be asymptomatic, UGE and histopathological examination may reveal upper gastrointestinal abnormalities and aid to a better assessment and management of IBD patients.

HIF-PHD inhibitor desidustat ameliorates iron deficiency anemia

Iron deficiency anemia is caused by many pathological conditions like chronic kidney disease (CKD), inflammation, malnutrition and gastrointestinal abnormality. Current treatments that are erythropoiesis stimulating agents (ESAs) and iron supplementation are inadequate and often lead to tolerance and/or toxicity. Desidustat, a prolyl hydroxylase (PHD) inhibitor, is clinically used for the treatment of anemia with CKD. In this study, we investigated the effect of desidustat on iron deficiency anemia (IDA). IDA was induced in C57BL6/J mice by iron deficient diet feeding. These mice were then treated with desidustat (15 mg/kg, PO) and FeSO4 (20 mg/kg) for five weeks and effect of the treatment on hematology, iron homeostasis, and bone marrow histology was observed. Effect of desidustat on iron metabolism in inflammation (LPS)-induced iron deficiency was also assessed. Both, Desidustat and FeSO4, increased MCV (mean corpuscular volume), MCH (mean corpuscular hemoglobin), hemoglobin, and HCT (hematocrit) in blood and increased iron in serum, liver, and spleen. Desidustat increased MCHC (mean corpuscular hemoglobin concentration) while FeSO4 treatment did not alter it. FeSO4 treatment significantly increased iron deposition in liver, and spleen, while desidustat increased iron in circulation and demonstrated efficient iron utilization. Desidustat increased iron absorption, serum iron and decreased hepcidin without altering tissue iron, while FeSO4 increased serum and tissue iron by increasing hepcidin in LPS-induced iron deficiency. Desidustat increased erythroid population, especially iron-dependent polychromatic normoblasts and orthochromatic normoblasts, while FeSO4 did not improve cell architecture. PHD inhibition by desidustat improved iron utilization in iron deficiency anemia, by efficient erythropoiesis.

Confirmation and expansion of the phenotype of the TCEAL1-related neurodevelopmental disorder

Numerous contiguous gene deletion syndromes causing neurodevelopmental disorders have previously been defined using cytogenetics for which only in the current genomic era the disease-causing genes have become elucidated. One such example is deletion at Xq22.2, previously associated with a neurodevelopmental disorder which has more recently been found to be caused by de novo loss-of-function variants in TCEAL1. So far, a single study reported six unrelated individuals with this monogenetic disorder, presenting with syndromic features including developmental delay especially affecting expressive speech, intellectual disability, autistic-like behaviors, hypotonia, gait abnormalities and mild facial dysmorphism, in addition to ocular, gastrointestinal, and immunologic abnormalities. Here we report on four previously undescribed individuals, including two adults, with de novo truncating variants in TCEAL1, identified through trio exome or genome sequencing, further delineating the phenotype of the TCEAL1-related disorder. Whereas overall we identify similar features compared to the original report, we also highlight features in our adult individuals including hyperphagia, obesity, and endocrine abnormalities including hyperinsulinemia, hyperandrogenemia, and polycystic ovarian syndrome. X chromosome inactivation and RNA-seq studies further provide functional insights in the molecular mechanisms. Together this report expands the phenotypic and molecular spectrum of the TCEAL1-related disorder which will be useful for counseling of newly identified individuals and their families.

The multisystem deformities features of Klippel-Feil syndrome patients combined with congenital scoliosis

Objective: To summarize the characteristics of multisystem deformities in patients with Klippel-Feil syndrome (KFS) combined with congenital scoliosis (CS). Methods: Within the framework of the "Deciphering Disorders Involving Scoliosis and Comorbidities (DISCO)" research collaboration, a retrospective analysis was conducted on patients diagnosed with KFS and CS at Peking Union Medical College Hospital between April 2005 and August 2022. Patient data, including imaging examinations and medical records, were collected to summarize the spinal and associated deformities. Results: A total of 82 KFS patients with concurrent CS were included, comprising 42 males and 40 females. The average age was (12.8±8.9) years. Among the KFS patients, there were 31 cases of Type Ⅰ, 12 cases of Type Ⅱ, and 39 cases of Type Ⅲ. The most common location for the major curve of scoliosis was the mid-thoracic segment (42 cases, 51.2%). Hemivertebrae deformities were most frequently observed in the upper thoracic segment (31 cases, 60.8%). There were no statistically significant differences in age, gender, major curve Cobb angle, or region of hemivertebrae occurrence among the different types of KFS (all P>0.05). Apart from spinal vertebral deformities, intraspinal deformities had the highest comorbidity rate (33 cases, 40.2%). The subjects were divided into two groups based on the presence or absence of intraspinal deformity (absence as group G0, presence as group G1), there was a statistically significant difference in the main Cobb angle [M(Q1, Q3)] between the two groups, which was 45.0° (27.5°, 62.0°) and 60.0° (37.5°, 83.5°), respectively (P=0.044). Additionally, a portion of the patients had concurrent cardiovascular system abnormalities (13 cases, 15.9%), craniofacial-ocular-auricular abnormalities (8 cases, 9.8%), genitourinary system abnormalities (7 cases, 8.5%), and gastrointestinal abnormalities (2 cases, 2.4%). Conclusions: Patients with KFS combined with CS commonly present with a major curve of spinal deformity in the mid-thoracic segment and often have comorbidities involving multiple systems. When combined with intraspinal anomalies, the major curve exhibits a greater degree of curvature.

Outcomes and characteristics in term infants with necrotising enterocolitis and CHD.

CHD is a significant risk factor for the development of necrotising enterocolitis. Existing literature does not differentiate between term and preterm populations. Long-term outcomes of these patients are not well understood. The aim was to investigate the baseline characteristics and outcomes of term normal birth weight infants with CHD who developed necrotising enterocolitis. A retrospective review was performed of infants from a single tertiary centre with CHD who developed necrotising enterocolitis of Bell's Stage 1-3, over a ten-year period. Inclusion criteria was those born greater than 36 weeks' gestation and birth weight over 2500g. Exclusion criteria included congenital gastro-intestinal abnormalities. Sub-group analysis was performed using Fisher's exact test. Twenty-five patients were identified, with a median gestational age of 38 weeks. Patients with univentricular physiology accounted for 32% (n = 8) and 52% of patients (n = 13) had a duct-dependent lesion. Atrioventricular septal defect was the most common cardiac diagnosis (n = 6, 24%). Patients with trisomy 21 accounted for 20% of cases. Mortality within 30 days of necrotising enterocolitis was 20%. Long-term mortality was 40%, which increased with increasing Bell's Stage. In total, 36% (n = 9) required surgical management of necrotising enterocolitis, the rate of which was significantly higher in trisomy 21 cases (p < 0.05). Not previously described in term infants is the high rate of trisomy 21 and atrioventricular septal defect. This may reflect higher baseline incidence in our population. Infants with trisomy 21 were more likely to develop surgical necrotising enterocolitis. Mortality at long-term follow-up was high in patients with Bell's Stage 2-3.

Mermaid baby: Fairy tale in practical

Sirenomelia, also called Mermaid syndrome is a rare and fatal anomaly which is characterized by a single lower extremity featuring a Mermaid like appearance where head and trunk is like humans and lower extremity is like tail of a fish. It is associated with other gastro-intestinal, genito-urinary and other organ abnormalities. Most patients die shortly after birth. The exact cause of Sirenomelia is unknown. Here we present a newborn baby with Sirenomelia. Mother had bad obstetric history, antenatal ultrasonography revealed severe oligohydramnios and renal agenesis. On examination there was dysmorphic facies, fusion of lower limbs, single leg with two foot and ten toes. There was no identical external genitalia and anus.

The Upper-gastrointestinal Endoscopic Findings of People Living with HIV: A Systematic Review.

This article aimed to analyze upper endoscopic findings in the HIV patient population to elucidate the upper-gastrointestinal complications related to HIV infection. Gastrointestinal (GI) disorders in individuals living with HIV/AIDS exhibit diverse and often nonspecific manifestations, imposing substantial morbidity and mortality burdens. Endoscopic evaluation with biopsies is essential in the diagnosis and management of these conditions. Delayed treatment due to undetected GI abnormalities during endoscopic examinations can lead to poorer health outcomes. This systematic review has determined the findings of upper-GI endoscopy of HIV-infected patients. Online databases of PubMed, Web of Science, Jisc Library Hub Discover, and Library of Congress have been searched using relevant keyword combinations. We have retrieved all the pertinent papers and reports published in English and screened them against inclusion/exclusion criteria for data extraction in two steps. First, titles/abstracts have been evaluated and then full-text screening has been performed by independent researchers. This study has adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist. In this review, 24 articles have been included in the final analysis. The study has focused on the characteristics of participants and the findings of endoscopic evaluations. The participants of the study have been HIV-positive patients, and the majority of them have undergone endoscopy due to gastrointestinal symptoms. The biopsy regions primarily targeted have been observed to be the esophagus, stomach, and duodenum. The most common result of the biopsy specimens has been chronic active gastritis. To improve clinical practice, this systematic review sought to provide an up-to-date reference for upper gastrointestinal endoscopic findings of HIV-infected persons. Our results are in line with earlier research showing how effective endoscopy is for determining a precise diagnosis and directing care. The majority of HIV patients with gastrointestinal symptoms have been found to have opportunistic infections and persistent active gastritis as well as mucosal abnormalities of the upper gastrointestinal tract. Studies have shown that endoscopic and histological assessment can aid in the early detection and management of issues involving the upper gastrointestinal tract.

Evaluation of the bacteriological quality of underground well water in Oyi local government area of Anambra State, Nigeria

Background: Water is indispensable for man’s existence on earth. In urban and predominantly rural communities in Nigeria, with over 85% of the population living below an average income, traditional drinking water sources such as open reservoirs, springs and open wells are still being used. The study assessed the bacteriological qualities of underground well water in Oyi L.G.A of Anambra State. Methods: Water samples collected by random sampling from various wells in the selected thirteen (13) wards of the study area were subjected to bacteriological analysis using standard methods. The bacteriological analysis examined differential and presumptive coliform counts. Confirmatory coliform tests were carried out using a loopful of presumptive positive and negative tests already sub-cultured on MacConkey agar plate and incubated at 37 0c for 24 hours to obtain bacterial isolates. Results: Escherichia coli was the most frequently occurring isolate of all the bacteria identified. Other isolates include Streptococcus spp., Staphylococcus aureus, Shigella spp., Enterococcus spp., Salmonella spp., Pseudomonas spp., Proteus spp. and Bacillus spp. The majority of these organisms are Gram-negative microorganisms which are most times implicated in gastrointestinal abnormalities. Conclusions: There is a high incidence of contamination of well waters by pathogenic organisms in most well waters from the Study area. Underground well water sources to be utilized for domestic purposes such as cooking should be treated or disinfected before use, either by boiling and filtration or by chemical sterilization or a combination of both.

Genomics of Re-Emergent Aeromonas salmonicida in Atlantic Salmon Outbreaks.

Furunculosis, caused by Aeromonas salmonicida, poses a significant threat to both salmonid and non-salmonid fish in diverse aquatic environments. This study explores the genomic intricacies of re-emergent A. salmonicida outbreaks in Atlantic salmon (Salmo salar). Previous clinical cases have exhibited pathological characteristics, such as periorbital hemorrhages and gastrointestinal abnormalities. Genomic sequencing of three Chilean isolates (ASA04, ASA05, and CIBA_5017) and 25 previously described genomes determined the pan-genome, phylogenomics, insertion sequences, and restriction-modification systems. Unique gene families have contributed to an improved understanding of the psychrophilic and mesophilic clades, while phylogenomic analysis has been used to identify mesophilic and psychrophilic strains, thereby further differentiating between typical and atypical psychrophilic isolates. Diverse insertion sequences and restriction-modification patterns have highlighted genomic structural differences, and virulence factor predictions can emphasize exotoxin disparities, especially between psychrophilic and mesophilic strains. Thus, a novel plasmid was characterized which emphasized the role of plasmids in virulence and antibiotic resistance. The analysis of antibiotic resistance factors revealed resistance against various drug classes in Chilean strains. Overall, this study elucidates the genomic dynamics of re-emergent A. salmonicida and provides novel insights into their virulence, antibiotic resistance, and population structure.

CAMTA1-related disorder: Phenotypic and molecular characterization of 26 new individuals and literature review.

Calmodulin-binding transcriptional activator 1 (CAMTA1) is highly expressed in the brain and plays a role in cell cycle regulation, cell differentiation, regulation of long-term memory, and initial development, maturation, and survival of cerebellar neurons. The existence of human neurological phenotypes, including cerebellar dysfunction with variable cognitive and behavioral abnormalities (CECBA), associated with CAMTA1 variants, has further supported its role in brain functions. In this study, we phenotypically and molecularly characterize the largest cohort of individuals (n = 26) with 23 novel CAMTA1 variants (frameshift-7, nonsense-6, splicing-1, initiation codon-1, missense-5, and intragenic deletions-3) and compare the findings with all previously reported cases (total = 53). We show that the most notable phenotypic findings are developmental delay/intellectual disability, unsteady or uncoordinated gait, hypotonia, behavioral problems, and eye abnormalities. In addition, there is a high incidence of dysarthria, dysgraphia, microcephaly, gastrointestinal abnormalities, sleep difficulties, and nonspecific brain MRI findings; a few of which have been under-reported. More than one third of the variants in this cohort were inherited from an asymptomatic or mildly affected parent suggesting reduced penetrance and variable expressivity. Our cohort provides a comprehensive characterization of the spectrum of phenotypes and genotypes among individuals with CECBA and the large data will facilitate counseling and formulating management plans and surveillance recommendations for these individuals.

Nintedanib solid lipid nanoparticles improve oral bioavailability and ameliorate pulmonary fibrosis in vitro and in vivo models

Nintedanib (NIN) and pirfenidone are the only approved drugs for the treatment of Idiopathic Pulmonary Fibrosis (IPF). However, NIN and pirfenidone have low oral bioavailability and limited therapeutic potential, requiring higher dosages to increase their efficacy, which causes significant liver and gastrointestinal toxicities. In this study, we aimed to develop nintedanib-loaded solid lipid nanoparticles (NIN-SLN) to improve the oral bioavailability and therapeutic potential against TGF-β-induced differentiation in IPF fibroblasts and bleomycin (BLM)-induced lung fibrosis in rat models. NIN-SLN was prepared using a double-emulsification method and characterization studies (Particle size, zeta potential, entrapment efficiency and other parameters) were performed using various techniques. NIN-SLN treatment significantly (p < 0.001) downregulated α-SMA and COL3A1 expression in TGF-β stimulated DHLF and LL29 cells. NIN-SLN showed a 2.87-fold increase in the bioavailability of NIN and also improved the NIN levels in lung tissues compared to NIN alone. Pharmacodynamic investigation revealed that NIN-SLN (50 mg/Kg) treatment significantly attenuated BLM-induced lung fibrosis by inhibiting epithelial-to-mesenchymal-transition (EMT), extracellular matrix remodelling, and collagen deposition compared to free NIN. Additionally, in the BLM model of fibrosis, NIN-SLN greatly improved the BLM-caused pathological changes, attenuated the NIN-induced gastrointestinal abnormalities, and significantly improved the lung functional indices compared to free NIN. Collectively, NIN-SLN could be a promising nanoformulation for the management of pulmonary fibrosis.

Causes of Iron Deficiency Anemia in Children Less Than 12 Years Old at Cooper University Hospital and Their Response to Intravenous Iron Replacement

Title of project: Causes of iron deficiency anemia in children less than 12 years old at Cooper University Hospital and their response to intravenous iron Background: Iron deficiency anemia (IDA) is the most common type of anemia in children. Even among industrialized countries like the US, IDA affects many children. Serious adverse outcomes can occur in children with IDA including, cognitive and motor neurodevelopmental delays which may be irreversible. While poor oral intake tends to be the focus of screening and preventative measures, additional causes of IDA include malabsorption from gastrointestinal abnormalities, medications that decrease iron absorption, parasitosis, genitourinary loss, and blood loss. Menorrhagia is a common cause of IDA among adolescents. The average age of menarche for adolescent girls is 12.43 years. Therefore, on data evaluation for the cause of IDA among patients aged 1-21, menstrual bleeding was overrepresented. Objective: This sub-analysis of a single center retrospective chart review analyzed the causes of IDA among children less than 12 years of age at Cooper University Hospital and their response to intravenous iron treatment. Methods: Data on all patients 1-12 years old who received intravenous iron infusions at Cooper University Hospital for IDA between 2016 and 2021 was analyzed. Descriptive statistics on the etiology of IDA and paired t-tests comparing pre-infusion hematologic parameters (hemoglobin, RDW, RBC, MCV, iron, ferritin, TIBC, percent saturation) to post-infusion values were conducted. Results: From the 150 patients included in the original study, 26 patients were 12 years of age or younger. The causes of IDA among these patients included inadequate dietary intake (65.4%), inflammatory bowel disease (15.4%), menorrhagia (15.4%) and one patient with factor II deficiency (3.8%). These patients required between one to eleven infusions to return to normal lab values. When comparing pre-infusion to post-final infusion lab values, there was significant improvement in all values (ferritin, iron, hemoglobin, MCV and RBCs) except total iron binding capacity, RDW and percent saturation. Discussion: Inadequate dietary intake was the most common cause of IDA in children less that 12 years old treated at Cooper University Hospital. Other causes included inflammatory bowel disease, menorrhagia and factor II deficiency. In contrast, the most common cause of IDA in children 12 and older was menorrhagia. Childhood food insecurity has been linked to IDA among low-income patients in the United States. Despite food assistance programs and adequate dietary education, patients continue to remain iron deficient. The current first-line therapy at Cooper University Hospital is oral iron supplementation. However, many patients fail the oral iron trial due to non-adherence, children spitting up or refusing to take the medication, and gastrointestinal side effects. Many pediatric patients in our clinic population are on NJ state insurance which requires a failed oral iron therapy trial prior to qualifying for coverage of intravenous iron. Yet, in a previous retrospective study completed in our clinic, intravenous iron has proven to be effective and safe, with fewer side effects and better adherence. For many patients, especially infants and toddlers, intravenous iron may provide a quicker cure for IDA, preventing irreversible neurodevelopmental delays. We propose that treatment with oral iron and intravenous iron should both be considered for first-line therapies and should be a shared decision between parents and providers.