Gastrointestinal Abnormalities Research Articles

Ketogenic diet treatment for super-refractory status epilepticus in the intensive care unit: feasibility, safety and effectiveness

Background and aimsTo investigate the feasibility, safety and effectiveness of the ketogenic diet (KD) for super-refractory status epilepticus (SRSE) in the intensive care unit (ICU).MethodsWe conducted a prospective investigation on patients with SRSE treated with the KD. The primary outcome measures were ketosis development as a biomarker of feasibility and resolution of SRSE as effectiveness. KD-related side effects were also investigated.ResultsTwelve patients (9 females and 3 males) with SRSE, with a median age of 34 years [range 16–69, interquartile range (IQR) 18–52], were treated with a KD. The median duration of SRSE prior to KD treatment was 21 days (range 4–46). SRSE resolved in 75% (9/12) of patients at a median of 3 days (range 1–18) after KD initiation. Among the nine KD responders, all were successfully weaned off anesthetic agents at a median of 16 days (range 4–32) after KD initiation, and all were also successfully weaned off ventilator. Side effects varied, and included gastrointestinal intolerances, malnutrition and metabolic abnormalities, electrolyte disturbance, and acute weight loss, although most of them could be corrected. No patient died due to KD, and neurofunctions continued to improve under KD therapy.ConclusionThe KD may be feasible and effective for the treatment of SRSE in the ICU. Moreover, it is relatively safe. However, there are numerous adverse events that can be corrected under close monitoring.

A New Case of Kilquist's Syndrome with a Novel Variant in SLC12A2 and a Brief Review of the Literature

Abstract Background Kilquist's syndrome is a recently described rare disease characterized by hearing loss, secretory dysfunction, gastrointestinal system abnormalities, and neurological anomalies including hypotonia and global developmental delay. It is caused by mutations in the solute carrier family 12 member 2 (SLC12A2) gene, which encodes the Na-K-2Cl cotransporter isoform 1 (NKCC1). Objective The aim of this study was to contribute to understanding the genotype–phenotype correlations of SLC12A2 variants. Material and Methods We evaluated a Turkish patient with a novel variant in SLC12A2 and reviewed all previously reported cases with Kilquist's syndrome. Whole exome sequencing and Sanger sequencing were used as molecular genetic testing methods. Results Whole exome sequencing revealed a nonsense homozygous NM_001046.3: c.2534G > A (pW845*) variant in the SLC12A2 gene. Sanger sequencing confirmed the variant. The patient was homozygous for this variant; the parents were heterozygous. Conclusion This is the first Turkish patient with a novel variant in SLC12A2 reported in the literature. With this report, we have contributed to expanding the clinical and mutation spectrum of SLC12A2.

Allgrove syndrome in endocrinology: Difficulties of diagnosis and treatment features. Case report

Allgrove syndrome is a rare autosomal recessive disorder characterized by the achalasia, alacrimia, adrenal insufficiency, which gave the additional and more recognizable name of this pathology – “Triple-A syndrome”. The clinical presentation of classical signs and symptoms of the syndrome is dependent on the age of the patient. Ophthalmological abnormalities are usually present at birth, whereas adrenal and gastrointestinal abnormalities are apparent after six months to the first decade of life. Neurological dysfunction from the involvement of central or autonomic nervous systems is also common with Allgrove syndrome observed during the adolescent period. Genetic analysis and detection of the AAAS gene mutation is the main step in the diagnosis of the syndrome. The presented clinical case will demonstrate the difficulties in making a diagnosis, choosing a treatment strategy for a patient with a long history of Allgrove syndrome.

After Foreign Body Ingestion: Waiting is not Always Disastrous

Background: Foreign bodies are objects with both organic and inorganic nature which originate from outside the human body. Due to ingestion, the gastrointestinal tract has become more prone mostly affecting paediatrics as compared to the adult population. Children with gastro-intestinal abnormalities including stenotic lesions and a history of Tracheoesophageal fistula are at increased risk of both occurrence and complications. The type, size, chemical properties of the object and the site of lodgment; all determine the clinical presentations. A history surrounding the circumstances, clinical presentations and radiological investigations are the pillars for diagnosis formulation. Besides the expectant and minimally invasive treatments, invasive modalities can also be employed especially in the presence of complications. Case presentation: A 3-year-old boy was brought to our hospital with a history of retching, hyper-salivation and inability to tolerate oral feeding as preceded by circumstances pointing towards gastrointestinal foreign body ingestion. An X-ray was suggestive of a gastrointestinal circular radio-opaque foreign body more likely at the level of duodenum in keeping with the coin. As he had no mechanical obstructive features, expectant management was done of which four days later he had a simultaneous passage of a 200 Tanzanian shilling’s coin on defecation. Conclusion: Early diagnosis, determining the surrounding circumstances and type of the foreign body ingested are the cornerstones for management modalities and outcomes. Both minimal and invasive approaches can be used, but the power of watchful waiting should not be underestimated as it can well be guided by the nature of the objects and the patient’s clinical presentations

Cyclic Vomiting Syndrome in Patients Affected by Jansen-de Vries Syndrome: Results From an International Survey.

Jansen-de Vries syndrome (JdVS) is an autosomal dominant neurodevelopmental disorder with intellectual disability and gastrointestinal (GI) abnormalities, including recurrent vomiting. This study aimed to understand the frequency and severity of GI symptoms in JdVS patients and to investigate the potential association with cyclic vomiting syndrome (CVS), which has not been previously reported. An international online survey assessed the prevalence and features of CVS and GI disorders in JdVS patients using Rome IV Criteria. The anonymous survey was conducted via Google Forms in April 2021. A total of 21 patients/guardians responded to the survey. The average age at JdVS diagnosis was 8.22 years (range: 1-42). Of the respondents, 6 (28.5%) had a CVS diagnosis, 5 (23.8%) had migraine, and 2 (9.5%) had abdominal migraine. Additionally, 8 (38%) had gastroesophageal reflux disease (GERD) and 8 (38%) had functional constipation. An analysis targeted questions showed that 7 (33%) met the Rome IV Criteria for CVS but were undiagnosed, leading to a CVS prevalence of 61% in this cohort. This study highlights a high prevalence of CVS in JdVS patients and underscores the need for increased awareness and accurate diagnosis to address misdiagnosis.

Conditional deletion of IP3R1 by Islet1-Cre in mice reveals a critical role of IP3R1 in interstitial cells of Cajal in regulating GI motility.

Inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) has been proposed to play a physiological role in regulating gastrointestinal (GI) motility, but the underlying cell-dependent mechanism remains unclear. Here, we utilized cell-specific IP3R1 deletion strategies to address this question in mice. Conditional IP3R1 knockout mice using Wnt1-Cre, Islet1-Cre mice, and smMHC-CreEGFP were generated. Cell lineage tracing was performed to determine where gene deletion occurred in the GI tract. Whole-gut transit assay and isometric tension recording were used to assess GI function in vivo and in vitro. In the mouse GI tract, Islet1-Cre targeted smooth muscle cells (SMCs) and interstitial cells of Cajal (ICCs), but not enteric neurons. IP3R1 deletion by Islet1-Cre (isR1KO) caused a phenotype of intestinal pseudo-obstruction (IPO), evidenced by prolonged whole-gut transit time, enlarged GI tract, abdominal distention, and early lethality. IP3R1 deletion by Islet1-Cre not only reduced the frequency of spontaneous contractions but also decreased the contractile responses to the muscarinic agonist carbachol (CCh) and electrical field stimulation (EFS) in colonic circular muscles. By contrast, smMHC-CreEGFP only targeted SMCs in the mouse GI tract. Although IP3R1 deletion by smMHC-CreEGFP (smR1KO)also reduced the contractile responses to CCh and EFS in colonic circular muscles, the frequency of spontaneous contractions was less affected, and neither global GI abnormalities nor early lethality was found in smR1KO mice. IP3R1 deletion in both ICCs and SMCs but not in SMCs alone causes an IPO phenotype, suggesting that IP3R1 in ICCs plays an essential role in regulating GI motility in vivo.

The Analysis of the Fetal Abdominal Wall and Gastrointestinal Tract Abnormalities in a Single Tertiary Center

OBJECTIVE: We aimed to evaluate the fetuses with gastrointestinal anomalies and anterior abdominal wall defects detected in the prenatal period in our clinic and to analyze their perinatal outcomes. STUDY DESIGN: This retrospective study analyzed the data of 67 cases evaluated by the perinatology department of the Basaksehir Cam and Sakura City Hospital between January 2021 and May 2023 with a diagnosis of fetal anterior abdominal wall and gastrointestinal tract abnormalities. RESULTS: A total of 67 cases were included in our study with a mean maternal age of 26.4 ± 3.1 years and a median gestational week of first assessment at our center of 22 weeks (12-39 weeks). The most common anterior abdominal wall malformations were omphalocele (n=29, 43.3%) and gastroschisis (6 cases, 9.0%), and the most common fetal gastrointestinal tract anomalies were duodenal atresia (n=10, 14.9%), dilated bowel (n=5, 7.4%), and intestinal atresia (n=4, 5.9%). While genetic testing was carried out in 18 cases (27%), chromosomal abnormality was found in 6 (9.0%) cases. Termination of pregnancy was performed in 6 cases (9.0%). Postnatally, surgery was performed in 49 cases (73.1%) with a diagnosis of postpartum omphalocele, duodenal atresia, gastroschisis, intestinal and anal atresia. An uneventful surgical course was recorded for 47 cases that underwent surgery. CONCLUSION: The most common abdominal wall defects are omphalocele and gastroschisis, and the most frequent gastrointestinal anomalies are small bowel abnormalities (duodenal atresia, dilated bowel, intestinal atresia) in our study cohort. These abnormalities might be an isolated anomaly or part of a syndrome or associated with chromosomal abnormalities. The prognosis for infants with gastrointestinal malformation depends on the presence of associated anomalies or karyotype anomalies.

Epigenomic and phenotypic characterization of DEGCAGS syndrome.

Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities syndrome (DEGCAGS, MIM #619488) is caused by biallelic, loss-of-function (LoF) ZNF699 variants, and is characterized by variable neurodevelopmental disability, discordant organ anomalies among full siblings and infant mortality. ZNF699 encodes a KRAB zinc finger protein of unknown function. We aimed to investigate the genotype-phenotype spectrum of DEGCAGS and the possibility of a diagnostic DNA methylation episignature, to facilitate the diagnosis of a highly variable condition lacking pathognomonic clinical findings. We collected data on 30 affected individuals (12 new). GestaltMatcher analyzed fifty-three facial photographs from five individuals. In nine individuals, methylation profiling of blood-DNA was performed, and a classification model was constructed to differentiate DEGCAGS from controls. We expand the ZNF699-related molecular spectrum and show that biallelic, LoF, ZNF699 variants cause unique clinical findings with age-related presentation and a similar facial gestalt. We also identified a robust episignature for DEGCAGS syndrome. DEGCAGS syndrome is a clinically variable recessive syndrome even among siblings with a distinct methylation episignature which can be used as a screening, diagnostic and classification tool for ZNF699 variants. Analysis of differentially methylated regions suggested an effect on genes potentially implicated in the syndrome's pathogenesis.

Genotype‐phenotype associations in individuals with Diamond Blackfan anaemia

AbstractIntroductionDiamond Blackfan anaemia (DBA) is a rare disorder characterized by failure of red blood cell production, congenital abnormalities and cancer predisposition, primarily caused by pathogenic germline variants in genes encoding ribosomal proteins.MethodsWe conducted a genotype‐phenotype and outcome study of 121 patients with DBA spanning the 20‐year history of the National Cancer Institute's Inherited Bone Marrow Failure Syndromes study. Patient phenotypes were compared by large versus small ribosomal protein genes, across genes with >5 cases (RPS19, RPS29, RPS26 and RPL35A) and by type of pathogenic variants (hypomorphic versus null, large deletions versus others).ResultsA pathogenic germline variant was identified in 71% of patients (n = 86/121) from 54 families. After adjusting for multiple testing, we found that patients with RPS29 variants were least likely to need treatment for anaemia while those with large ribosomal protein subunit variants had a higher proportion of intellectual disability and gastrointestinal abnormalities compared with small ribosomal protein subunit variants (p < 3.5 × 10−4). There were no statistically significant differences in overall survival or cancer incidence among patients with large or small ribosomal subunit genes.ConclusionThis detailed genotype‐phenotype study of DBA improves our understanding of the role of germline genetics in the clinical manifestations that may help guide the management of people with DBA.

Analysis of Gut Bacterial and Fungal Microbiota in Children with Autism Spectrum Disorder and Their Non-Autistic Siblings.

Autism Spectrum Disorder (ASD) is a multifactorial disorder involving genetic and environmental factors leading to pathophysiologic symptoms and comorbidities including neurodevelopmental disorders, anxiety, immune dysregulation, and gastrointestinal (GI) abnormalities. Abnormal intestinal permeability has been reported among ASD patients and it is well established that disturbances in eating patterns may cause gut microbiome imbalance (i.e., dysbiosis). Therefore, studies focusing on the potential relationship between gut microbiota and ASD are emerging. We compared the intestinal bacteriome and mycobiome of a cohort of ASD subjects with their non-ASD siblings. Differences between ASD and non-ASD subjects include a significant decrease at the phylum level in Cyanobacteria (0.015% vs. 0.074%, p < 0.0003), and a significant decrease at the genus level in Bacteroides (28.3% vs. 36.8%, p < 0.03). Species-level analysis showed a significant decrease in Faecalibacterium prausnitzii, Prevotella copri, Bacteroides fragilis, and Akkermansia municiphila. Mycobiome analysis showed an increase in the fungal Ascomycota phylum (98.3% vs. 94%, p < 0.047) and an increase in Candida albicans (27.1% vs. 13.2%, p < 0.055). Multivariate analysis showed that organisms from the genus Delftia were predictive of an increased odds ratio of ASD, whereas decreases at the phylum level in Cyanobacteria and at the genus level in Azospirillum were associated with an increased odds ratio of ASD. We screened 24 probiotic organisms to identify strains that could alter the growth patterns of organisms identified as elevated within ASD subject samples. In a preliminary in vivo preclinical test, we challenged wild-type Balb/c mice with Delftia acidovorans (increased in ASD subjects) by oral gavage and compared changes in behavioral patterns to sham-treated controls. An in vitro biofilm assay was used to determine the ability of potentially beneficial microorganisms to alter the biofilm-forming patterns of Delftia acidovorans, as well as their ability to break down fiber. Downregulation of cyanobacteria (generally beneficial for inflammation and wound healing) combined with an increase in biofilm-forming species such as D. acidovorans suggests that ASD-related GI symptoms may result from decreases in beneficial organisms with a concomitant increase in potential pathogens, and that beneficial probiotics can be identified that counteract these changes.

A case report of elevated bromide levels from pyridostigmine bromide for treatment of myasthenia gravis.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Elevated serum bromide levels can cause dermatological, gastrointestinal, and neurological abnormalities. As bromide and chloride are both halogens, bromide may interfere with chloride assays, causing a falsely high serum chloride concentration and a low or negative anion gap. There is a paucity of data describing bromide toxicity from high doses of pyridostigmine bromide (PB). This case report describes a patient with an elevated bromide level with neurological symptoms from a therapeutic dose of PB. A 37-year-old male with myasthenia gravis secondary to type B2 thymoma status following thymectomy presented in myasthenic crisis. He required mechanical ventilation and was managed with steroids, intravenous immune globulin, plasmapheresis, and PB. On day 9, the patient experienced acute agitation. He had an anion gap of 2 mEq/L and a chloride concentration of 109 mEq/L. The plasma creatinine concentration was 0.63 to 1.15mg/dL and urine output was 0.76 to 1.79mL/kg/h throughout his admission. All other laboratory values were normal. The daily dose of PB was 660mg on day 9, but the patient received 76mg of intravenous PB over the first few days of his admission with the largest dose in 24 hours equal to 48mg. On day 10, the patient's bromide level was 37 μg/mL. His agitation was initially managed with quetiapine, followed by PB dose reduction. To our knowledge, there are 2 cases in the literature of bromide toxicity secondary to PB. These patients experienced neurological symptoms with bromide levels of 88 to 90 μg/mL. Bromide concentrations of more than 12 μg/mL are associated with a higher risk of neuronal dysfunction demonstrated as disturbances on an electroencephalogram, and levels greater than 50 μg/mL are considered toxic. While our patient's bromide level was not as high as those previously reported, no other causes for his agitation were identified. Elevated bromide levels from therapeutic PB can occur, and monitoring of these levels should be considered.

GastroFuse-Net: an ensemble deep learning framework designed for gastrointestinal abnormality detection in endoscopic images.

Convolutional Neural Networks (CNNs) have received substantial attention as a highly effective tool for analyzing medical images, notably in interpreting endoscopic images, due to their capacity to provide results equivalent to or exceeding those of medical specialists. This capability is particularly crucial in the realm of gastrointestinal disorders, where even experienced gastroenterologists find the automatic diagnosis of such conditions using endoscopic pictures to be a challenging endeavor. Currently, gastrointestinal findings in medical diagnosis are primarily determined by manual inspection by competent gastrointestinal endoscopists. This evaluation procedure is labor-intensive, time-consuming, and frequently results in high variability between laboratories. To address these challenges, we introduced a specialized CNN-based architecture called GastroFuse-Net, designed to recognize human gastrointestinal diseases from endoscopic images. GastroFuse-Net was developed by combining features extracted from two different CNN models with different numbers of layers, integrating shallow and deep representations to capture diverse aspects of the abnormalities. The Kvasir dataset was used to thoroughly test the proposed deep learning model. This dataset contained images that were classified according to structures (cecum, z-line, pylorus), diseases (ulcerative colitis, esophagitis, polyps), or surgical operations (dyed resection margins, dyed lifted polyps). The proposed model was evaluated using various measures, including specificity, recall, precision, F1-score, Mathew's Correlation Coefficient (MCC), and accuracy. The proposed model GastroFuse-Net exhibited exceptional performance, achieving a precision of 0.985, recall of 0.985, specificity of 0.984, F1-score of 0.997, MCC of 0.982, and an accuracy of 98.5%.

GastroNet: A CNN based system for detection of abnormalities in gastrointestinal tract from wireless capsule endoscopy images

Gastrointestinal disorders are a class of prevalent disorders in the world. Capsule endoscopy is considered an effective diagnostic modality for diagnosing such gastrointestinal disorders, especially in small intestinal regions. The aim of this work is to leverage the potential of deep convolutional neural networks for automated classification of gastrointestinal abnormalities from capsule endoscopy images. This method developed a deep learning architecture, GastroNetV1, an automated classifier, to detect abnormalities in capsule endoscopy images. The gastrointestinal abnormalities considered are ulcerative colitis, polyps, and esophagitis. The curated dataset consists of 6000 images with “ground truth” labeling. The input image is automatically classified as ulcerative colitis, a polyp, esophagitis, or a normal condition by a web-based application designed with the trained algorithm. The classifier produced 99.2% validation accuracy, 99.3% specificity, 99.3% sensitivity, and 0.991 AUC. These results exceed that of the state-of-the-art systems. Hence, the GastroNetV1 could be used to identify the different gastrointestinal abnormalities in the capsule endoscopy images, which will, in turn, improve healthcare quality.

Dyskeratosis congenita with squamous cell carcinoma of the tongue: A rare case report.

Dyskeratosis congenita is a rare inherited bone marrow failure disorder characterized by a classic triad: nail dystrophy, reticulate skin pigmentation, and oral leukoplakia. Patients with dyskeratosis congenita have also been described as having gastrointestinal, genitourinary, neurological, ophthalmic, pulmonary, and skeletal abnormalities. Also, 80% of patients are affected with oral leukoplakia and these areas are more prone to develop into oral squamous cell carcinoma. We hereby report a rare case of oral squamous cell carcinoma of the tongue in a young male patient with dyskeratosis congenita.

Protective effect of cholecalciferol against cobalt-induced neurotoxicity in rats: ZO-1/iFABP, ChAT/AchE and antioxidant pathways as potential therapeutic targets.

Cobalt (Co) toxicity has been reported to produce central nervous system and gastrointestinal abnormalities. This study assessed the therapeutic effect of cholecalciferol (Cho) supplementation against damages caused by sub-acute (14-day) cobalt chloride (CoCl2) exposure in the brain and intestines. Thirty-five male Wistar rats were divided equally into five groups: Group I (control) received no treatment; Group II received oral CoCl2 (100 mg/kg) only; Groups III, IV, and V received 1000, 3000 and 6000 IU/kg of cholecalciferol, respectively by oral gavage, and concurrently with CoCl2. Cobalt-treated rats showed neuronal vacuolation and presence of pyknotic nuclei in the cerebral cortex and hippocampus, depletion of Purkinje cells in the cerebellum, as well as inflammation and congestion in the intestinal mucosa. Cobalt also increased brain and intestinal hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations, while simultaneously reducing glutathione (GSH) content, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities. Further, CoCl2 induced increases in brain acetylcholinesterase (AchE) activity and serum zonulin (ZO-1) levels. Conversely, Cho administration suppressed CoCl2-induced damages in the brain and intestines by reducing lipid peroxidation and increasing the activities of antioxidant enzymes. Remarkably, Cho produced stimulation of brain choline acetyltransferase (ChAT) and suppression of AchE activity, along with dose-dependent reduction in serum levels of ZO-1, intestinal fatty acid-binding protein (iFABP) and nitric oxide. In conclusion, the protective role of cholecalciferol against cobalt-induced toxicity occurred via modulation of cholinergic, intestinal permeability and antioxidant pathways. The results may prove significant in the context of the role of gut-brain connections in neuroprotection.

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.