Endoscopic ultrasound-guided gastrojejunostomy for benign gastric outlet obstruction (GOO): a retrospective analysis of patients and outcomes.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) has been well utilized in treating malignant gastric outlet obstructions (GOO) given its efficacy and lower risk profile compared to surgery. However, its efficacy and potential for use in patients with benign GOO who are poor surgical candidates is not well documented. The aim of this study was to examine the role of EUS-GJ in treatment of benign GOO in select patients. PATIENTS AND METHODS: This is a single-center, open-label, retrospective descriptive study that included all consecutive patients undergoing EUS-GJ to treat benign causes of GOO. Direct antegrade and direct retrograde methods were utilized. RESULTS: A total of 18 patients were included, 38.9% female with an average age of 63.3 years. Extrinsic GOO was present in (10 of 18) 55.5% of patients and intrinsic etiology was present in (8 of 18) 45.5% of patients. Technical success was achieved in 100% (18 of 18) patients and clinical success was achieved in 94% (17 of 18) patients. In total, 13 patients had follow-up endoscopy, 2 patients were treated relatively recently in time, 1 patient was lost to follow-up, and 2 patients died of other chronic illnesses. Stents remained in place for a median of 286 days (range 88-1444 days). In patients whose stents were removed, 75% (3 of 4) had extrinsic etiologies of GOO. CONCLUSIONS: This study reports a favorable long-term patency with excellent technical and clinical success of EUS-GJ in patients with benign GOO. Despite the limitations of sample size and retrospective nature, it adds to the extremely limited literature of EUS-GJ in management of patients with benign GOO.

Structural basis of the oncogenic KRAS mutant and GJ101 complex.

KRAS mutations occur in a quarter of all human cancers. When activated in its GTP-bound form, RAS stimulates diverse cellular systems, such as cell division, differentiation, growth, and apoptosis through the activations of various signaling pathways, which include mitogen-activated protein kinase (MAPK), phosphoinositide 3 kinases (PI3K), and RAL-GEFs pathways. We found that GJ101 (65LYDVA69) binds directly to the KRAS mutant (G12V) and showed tumor-suppressive activity. In addition, the GJ101 peptide inhibited KRAS mutant as determined by a [α-32P] guanosine triphosphate (GTP) binding assay and suppressed pancreatic cell line in a cell proliferation assay. Herein, the complex structure of KRAS and GJ101 was clarified by X-ray crystallography. Isothermal titration calorimetry showed that GJ101 binds highly with KRAS mutant and the complex structure of KRAS G12V.GJ101 complex presented that the residue of Q61 directly interacted with L65 of GJ101. Overall, the results suggest GJ101 be considered a developmental starting point for KRAS G12V inhibitor.

Retrospective cohort comparison between fluoroscopic and radiograph-only exams for evaluation of gastrostomy and gastrojejunostomy tubes.

BACKGROUND: Gastrostomy (G) tube or gastrojejunostomy (GJ) tube checks are radiographic procedures that are frequently ordered to confirm tube positioning. OBJECTIVE: To characterize the sensitivity and specificity of radiograph-only examinations and traditional radiologist-performed fluoroscopy exams for G-tube or GJ-tube malposition and other adverse events detectable by imaging. MATERIALS AND METHODS: We performed a retrospective cohort study at a single tertiary pediatric center that included all subjects who underwent G-tube or GJ-tube checks using fluoroscopy or radiograph-only exams between January 1, 2008, and January 1, 2019. Radiograph-only examinations were defined as checks that consist of frontal and lateral abdominal radiographs after injection of contrast through the G-tube or GJ-tube. Fluoroscopy exams were defined as exams performed by a radiologist in the fluoroscopy suite. Radiology reports were evaluated for reported tube malposition and for other adverse events that are detectable by imaging. Clinical notes from the day of the procedure and longer-term clinical follow-up notes were used as a reference standard for adverse events. The sensitivity and specificity of the two procedures were calculated. RESULTS: A total of 212 exams, including 86 (41%) fluoroscopy exams and 126 (59%) radiograph-only exams, were evaluated. The most common correctly identified adverse event was tube malposition (9 true positives). The most commonly missed adverse event was leakage around the tube (8 false negatives). Fluoroscopy exams had a sensitivity of 100% (6/6; 95% CI: 100%, 100%) and a specificity of 100% (80/80; 95% CI: 100%, 100%) for tube malposition, while radiograph-only exams had 75% sensitivity (3/4; 95% CI: 33%,100%) and 100% specificity (112/112; 95% CI: 100%, 100%). CONCLUSIONS: Fluoroscopy and radiograph-only exams have similar sensitivity and specificity for detecting G-tube or GJ-tube malposition.

Volatile Organic Compounds of Bacillus velezensis GJ-7 against Meloidogyne hapla through Multiple Prevention and Control Modes.

The Bacillus velezensis GJ-7 strain isolated from the rhizosphere soil of Panax notoginseng showed high nematicidal activity and therefore has been considered a biological control agent that could act against the root-knot nematode Meloidogyne hapla. However, little was known about whether the GJ-7 strain could produce volatile organic compounds (VOCs) that were effective in biocontrol against M. hapla. In this study, we evaluated the nematicidal activity of VOCs produced by the fermentation of GJ-7 in three-compartment Petri dishes. The results revealed that the mortality rates of M. hapla J2s were 85% at 24 h and 97.1% at 48 h after treatment with the VOCs produced during GJ-7 fermentation. Subsequently, the VOCs produced by the GJ-7 strain were identified through solid-phase micro-extraction gas chromatography mass spectrometry (SPME-GC/MS). Six characteristic VOCs from the GJ-7 strain fermentation broth were identified, including 3-methyl-1-butanol, 3-methyl-2-pentanone, 5-methyl-2-hexanone, 2-heptanone, 2,5-dimethylpyrazine, and 6-methyl-2-heptanone. The in vitro experimental results from 24-well culture plates showed that the six volatiles had direct-contact nematicidal activity against M. hapla J2s and inhibition activity against egg hatching. In addition, 3-methyl-1-butanol and 2-heptanone showed significant fumigation effects on M. hapla J2s and eggs. Furthermore, all six of the VOCs repelled M. hapla J2 juveniles in 2% water agar Petri plates. The above data suggested that the VOCs of B. velezensis GJ-7 acted against M. hapla through multiple prevention and control modes (including direct-contact nematicidal activity, fumigant activity, and repellent activity), and therefore could be considered as potential biocontrol agents against root-knot nematodes.

Characterization and genomic analysis of the first Oceanospirillum phage, vB_OliS_GJ44, representing a novel siphoviral cluster.

BACKGROUND: Marine bacteriophages play key roles in the community structure of microorganisms, biogeochemical cycles, and the mediation of genetic diversity through horizontal gene transfer. Recently, traditional isolation methods, complemented by high-throughput sequencing metagenomics technology, have greatly increased our understanding of the diversity of bacteriophages. Oceanospirillum, within the order Oceanospirillales, are important symbiotic marine bacteria associated with hydrocarbon degradation and algal blooms, especially in polar regions. However, until now there has been no isolate of an Oceanospirillum bacteriophage, and so details of their metagenome has remained unknown. RESULTS: Here, we reported the first Oceanospirillum phage, vB_OliS_GJ44, which was assembled into a 33,786 bp linear dsDNA genome, which includes abundant tail-related and recombinant proteins. The recombinant module was highly adapted to the host, according to the tetranucleotides correlations. Genomic and morphological analyses identified vB_OliS_GJ44 as a siphovirus, however, due to the distant evolutionary relationship with any other known siphovirus, it is proposed that this virus could be classified as the type phage of a new Oceanospirivirus genus within the Siphoviridae family. vB_OliS_GJ44 showed synteny with six uncultured phages, which supports its representation in uncultured environmental viral contigs from metagenomics. Homologs of several vB_OliS_GJ44 genes have mostly been found in marine metagenomes, suggesting the prevalence of this phage genus in the oceans. CONCLUSIONS: These results describe the first Oceanospirillum phage, vB_OliS_GJ44, that represents a novel viral cluster and exhibits interesting genetic features related to phage-host interactions and evolution. Thus, we propose a new viral genus Oceanospirivirus within the Siphoviridae family to reconcile this cluster, with vB_OliS_GJ44 as a representative member.

Fusarium: more than a node or a foot-shaped basal cell.

Recent publications have argued that there are potentially serious consequences for researchers in recognising distinct genera in the terminal fusarioid clade of the family Nectriaceae. Thus, an alternate hypothesis, namely a very broad concept of the genus Fusarium was proposed. In doing so, however, a significant body of data that supports distinct genera in Nectriaceae based on morphology, biology, and phylogeny is disregarded. A DNA phylogeny based on 19 orthologous protein-coding genes was presented to support a very broad concept of Fusarium at the F1 node in Nectriaceae. Here, we demonstrate that re-analyses of this dataset show that all 19 genes support the F3 node that represents Fusarium sensu stricto as defined by F. sambucinum (sexual morph synonym Gibberella pulicaris). The backbone of the phylogeny is resolved by the concatenated alignment, but only six of the 19 genes fully support the F1 node, representing the broad circumscription of Fusarium. Furthermore, a re-analysis of the concatenated dataset revealed alternate topologies in different phylogenetic algorithms, highlighting the deep divergence and unresolved placement of various Nectriaceae lineages proposed as members of Fusarium. Species of Fusarium s. str. are characterised by Gibberella sexual morphs, asexual morphs with thin- or thick-walled macroconidia that have variously shaped apical and basal cells, and trichothecene mycotoxin production, which separates them from other fusarioid genera. Here we show that the Wollenweber concept of Fusarium presently accounts for 20 segregate genera with clear-cut synapomorphic traits, and that fusarioid macroconidia represent a character that has been gained or lost multiple times throughout Nectriaceae. Thus, the very broad circumscription of Fusarium is blurry and without apparent synapomorphies, and does not include all genera with fusarium-like macroconidia, which are spread throughout Nectriaceae (e.g., Cosmosporella, Macroconia, Microcera). In this study four new genera are introduced, along with 18 new species and 16 new combinations. These names convey information about relationships, morphology, and ecological preference that would otherwise be lost in a broader definition of Fusarium. To assist users to correctly identify fusarioid genera and species, we introduce a new online identification database, Fusarioid-ID, accessible at www.fusarium.org. The database comprises partial sequences from multiple genes commonly used to identify fusarioid taxa (act1, CaM, his3, rpb1, rpb2, tef1, tub2, ITS, and LSU). In this paper, we also present a nomenclator of names that have been introduced in Fusarium up to January 2021 as well as their current status, types, and diagnostic DNA barcode data. In this study, researchers from 46 countries, representing taxonomists, plant pathologists, medical mycologists, quarantine officials, regulatory agencies, and students, strongly support the application and use of a more precisely delimited Fusarium (= Gibberella) concept to accommodate taxa from the robust monophyletic node F3 on the basis of a well-defined and unique combination of morphological and biochemical features. This F3 node includes, among others, species of the F. fujikuroi, F. incarnatum-equiseti, F. oxysporum, and F. sambucinum species complexes, but not species of Bisifusarium [F. dimerum species complex (SC)], Cyanonectria (F. buxicola SC), Geejayessia (F. staphyleae SC), Neocosmospora (F. solani SC) or Rectifusarium (F. ventricosum SC). The present study represents the first step to generating a new online monograph of Fusarium and allied fusarioid genera (www.fusarium.org).

Gap junctional intercellular communication in adipose-derived stromal/stem cells is cell density-dependent and positively impacts adipogenic differentiation.

Adipose-derived stromal/stem cells (ASCs) represent a widely used cell source with multi-lineage differentiation capacity in approaches for tissue engineering and regenerative medicine. Despite the multitude of literature on their differentiation capacity, little is reported about the physiological properties contributing to and controlling the process of lineage differentiation. Direct intercellular communication between adjacent cells via gap junctions has been shown to modulate differentiation processes in other cell types, with connexin 43 (Cx43) being the most abundant isoform of the gap junction-forming connexins. Thus, in the present study we focused on the expression of Cx43 and gap junctional intercellular communication (GJIC) in human ASCs, and its significance for adipogenic differentiation of these cells. Cx43 expression in ASCs was demonstrated histologically and on the gene and protein expression level, and was shown to be greatly positively influenced by cell seeding density. Functionality of gap junctions was proven by dye transfer analysis in growth medium. Adipogenic differentiation of ASCs was shown to be also distinctly elevated at higher cell seeding densities. Inhibition of GJIC by 18α-glycyrrhetinic acid (AGA) significantly compromised adipogenic differentiation, as demonstrated by histology, triglyceride quantification, and adipogenic marker gene expression. Flow cytometry analysis showed a lower proportion of cells undergoing adipogenesis when GJIC was inhibited, further indicating the importance of GJIC in the differentiation process. Altogether, this study demonstrates the impact of direct cell-cell communication via gap junctions on the adipogenic differentiation process of ASCs, and may contribute to further integrate direct intercellular crosstalk in rationales for tissue engineering approaches.

Interaction of membrane/lipid rafts with the cytoskeleton: impact on signaling and function: membrane/lipid rafts, mediators of cytoskeletal arrangement and cell signaling.

The plasma membrane in eukaryotic cells contains microdomains that are enriched in certain glycosphingolipids, gangliosides, and sterols (such as cholesterol) to form membrane/lipid rafts (MLR). These regions exist as caveolae, morphologically observable flask-like invaginations, or as a less easily detectable planar form. MLR are scaffolds for many molecular entities, including signaling receptors and ion channels that communicate extracellular stimuli to the intracellular milieu. Much evidence indicates that this organization and/or the clustering of MLR into more active signaling platforms depends upon interactions with and dynamic rearrangement of the cytoskeleton. Several cytoskeletal components and binding partners, as well as enzymes that regulate the cytoskeleton, localize to MLR and help regulate lateral diffusion of membrane proteins and lipids in response to extracellular events (e.g., receptor activation, shear stress, electrical conductance, and nutrient demand). MLR regulate cellular polarity, adherence to the extracellular matrix, signaling events (including ones that affect growth and migration), and are sites of cellular entry of certain pathogens, toxins and nanoparticles. The dynamic interaction between MLR and the underlying cytoskeleton thus regulates many facets of the function of eukaryotic cells and their adaptation to changing environments. Here, we review general features of MLR and caveolae and their role in several aspects of cellular function, including polarity of endothelial and epithelial cells, cell migration, mechanotransduction, lymphocyte activation, neuronal growth and signaling, and a variety of disease settings. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé.

Reflux induces DNA strand breaks and expression changes of MMP1+9+14 in a human miniorgan culture model.

Gastroesophageal reflux disease has been implicated in the pathogenesis of adenocarcinoma of the oesophagus. The same applies to laryngopharyngeal reflux (LPR) and squamous cell cancer of the head and neck, but so far, this link has not been proven. The impact of low pH and bile acids has not been studied extensively in cells other than oesophageal cancer cell lines and tissue. The aims of this study were to investigate the pathogenic potential of reflux and its single components on the mucosa of the upper respiratory tract. We measured DNA stability in human miniorgan cultures (MOCs) and primary epithelial cell cultures (EpCs) in response to reflux by the alkaline comet assay. As matrix metalloproteinases (MMPs) are involved in extracellular matrix remodelling processes and may contribute to cancer progression, we studied the expression of MMP1, -9, and -14 in MOCs, EpC, UM-SCC-22B, and FADUDD. DNA strand breaks (DNA-SBs) increased significantly at low pH and after incubation with human or artificial gastric juice. Single incubation with glycochenodeoxycholic acid also showed a significant increase in DNA-SBs. In epithelial cell cultures, human gastric juice increased the number of DNA-SBs at pH 4.5 and 5.5. Artificial gastric juice significantly up regulated the gene expression of MMP9. Western blot analysis confirmed the results of gene expression analysis, but the up regulation of MMP1, -9, and -14 was donor-specific. Reflux has the ability to promote genomic instability and may contribute to micro environmental changes suitable for the initiation of malignancy. Further functional gene analysis may elucidate the role of laryngopharyngeal reflux in the development of head neck squamous cell carcinoma (HNSCC).

Isolation, identification, molecular and pathogenicity characteristics of an infectious laryngotracheitis virus from Hubei province, China.

Multiple outbreaks of avian infectious laryngotracheitis (ILT) in chickens, both domestically and internationally, have been directly correlate to widespread vaccine use in affected countries and regions. Phylogenetic and recombination event analyses have demonstrated that avian infectious laryngotracheitis virus (ILTV) field strains are progressively evolving toward the chicken embryo-origin (CEO) vaccine strain. Even with standardized biosecurity measures and effective prevention and control strategies implemented on large-scale farms, continuous ILT outbreaks result in significant economic losses to the poultry industry worldwide. These outbreaks undoubtedly hinder efforts to control and eradicate ILTV in the future. In this study, an ILTV isolate was successfully obtained by laboratory PCR detection and virus isolation from chickens that exhibited dyspnea and depression on a broiler farm in Hubei Province, China. The isolated strain exhibited robust propagation on chorioallantoic membranes of embryonated eggs, but failed to establish effective infection in chicken hepatocellular carcinoma (LMH) cells. Phylogenetic analysis revealed a unique T441P point mutation in the gJ protein of the isolate. Animal experiments confirmed the virulence of this strain, as it induced mortality in 6-wk-old chickens. This study expands current understanding of the epidemiology, genetic variations, and pathogenicity of ILTV isolates circulating domestically, contributing to the elucidate of ILTV molecular basis of pathogenicity and development of vaccine.

Magnetic compression anastomosis gastrojejunostomy: feasibility and efficacy of a novel device in a swine model.

BACKGROUND: Means of addressing technical challenges in forming gastrojejunostomy (GJ) anastomoses and maintaining their patency are sought. OBJECTIVES: Evaluation of preclinical feasibility and healing efficacy of a novel linear magnetic compression anastomosis (MCA) device to form a patent GJ versus sutured jejunal enterotomy (JE) sites in swine. SETTING: Single-center veterinary testing facility. METHODS: Feasibility of 3 prototype sizes (4, 6, and 8 cm) of a metal MCA device (MCAD) to form a patent GJ was evaluated over 6 weeks. A distal magnet was laparoscopically inserted in the jejunum, a proximal magnet was placed gastroscopically in the stomach; magnets were aligned to gradually form an anastomosis, self-detached, and be expelled. At necropsy, MCAs were assessed for patency and compared with JE tissues to evaluate wound healing. RESULTS: MCADs aligned at the GJ location without complications. In 5/6 MCAD pairs, dislodgement occurred between 7 and 26 days; expulsion 13-31 days; 1 MCAD pair was retained in the stomach. At necropsy, all pigs were healthy, gaining a mean 15.0 kg. Anastomoses were not adequately patent in 2/4 pigs receiving the 4-cm or 6-cm MCADs because their linear length was too small. But, anastomoses of both pigs receiving the 8-cm MCADs maintained full patency. Minimal inflammation and fibrosis were seen in MCA specimens versus sutured enterotomies. CONCLUSIONS: A novel linear MCA device was feasible and effectively created a patent GJ anastomosis in swine with minimal inflammation and fibrosis. The MCAD may be appropriate for clinical evaluation.

Neuroprotective effect of GJ-4 against cognitive impairments in vascular dementia by improving white matter damage.

BACKGROUND: White matter lesions (WMLs) are increasingly linked to the pathological process of chronic vascular dementia (VaD). An effective crocins fraction extracted from Gardenia Fructus, GJ-4, has been shown to improve cognitive function in several Alzheimer's disease models and VaD models. OBJECTIVES: To explore the potential mechanisms of GJ-4 on WMLs in a chronic VaD mouse model. METHODS: The chronic VaD mouse model was established, and WMLs were characterized by cerebral blood flow (CBF), behavioral tests, LFB staining, and immunohistochemistry. The anti-oxidative effect of GJ-4 was validated by examining biochemical parameters (SOD, MDA, and GSH) and the Keap1-Nrf2/HO-1 pathway. The impact of GJ-4 on lipid metabolism in WM was further investigated through lipidomic analysis. RESULTS: GJ-4 significantly attenuated cognitive impairments and improved the CBF of BCAS (bilateral common carotid artery stenosis)-induced mice. Mechanism research showed that GJ-4 could enhance cognition by promoting the repair of WMLs by inhibiting oxidative stress. Furthermore, GJ-4 treatment significantly reduced chronic cerebral hypoperfusion (CCH)-induced WMLs via improving lipid metabolism disorder in the WM. CONCLUSION: This research has provided valuable insights into the significance of WMLs in CCH-induced VaD and underscored the potential of GJ-4 as a therapeutic agent for improving cognitive function by targeting WMLs. These findings suggest that GJ-4 is a promising candidate for the treatment of VaD.

The Therapeutic Potential of Targeting the Connexin43 as a New Approach to Reducing Post-Surgical Adhesion.

Post-surgical peritoneal adhesions are a serious problem causing complications, such as bowel obstruction, infertility, and pain. There are currently no effective ways of preventing post-surgical adhesions. Excess secretion of proinflammatory cytokines and profibrotic molecules by immune cells and adherent fibroblasts is the main mechanism thatpromotes post-operative fibrotic scars. Although many studies have been conducted on the pathological causes of this disorder, there are still many unknown facts in this matter, so assessment of the role of different molecules in causing inflammation and adhesion can lead to the creation of new treatment methods. Connexins are a group of proteins related to gap junctions that have a role in cell communication and transmitted signaling between adjacent cells. Between different types of connexin protein isoforms, connexin43 is known to be involved in pathological conditions related to inflammation and fibrosis. Recent studies have reported that inhibition of connexin43 has the potential to reduce inflammation and fibrosis by reducing the expression of molecules like α-SMA and plasminogen activator inhibitor (PAI) that are involved in the early stages of adhesion formation. Further, inhibition of connexin43 may have therapeutic potential as a target to prevent post-surgical peritoneal adhesions.

Amelioration activity of the high bioaccessible chrysanthemum (Gongju) phenolics on alcohol-induced oxidative injury in AML-12 cells.

The main bioavailable phenolics from of Gongju (GJ) and their mechanism for hepato-protection remain unclear. To select the GJ phenolics with high bioavailability, chrysanthemum digestion and Caco-2 cells were used and their hepato-protective potential were examined by using AML-12 cells. The digestive recovery and small intestinal transit rate of the main phenolic compounds ranged from 28.52 to 69.53% and 6.57% âˆ¼ 15.50%, respectively. Among them, chlorogenic acid, 3,5-dicaffeoylquinic acid, and 1,5-dicaffeoylquinic acid, showed higher small intestinal transit rates and digestive recoveries. Furthermore, we found that by increasing intracellular Catalase (CAT) and Superoxide dismutase (SOD) viability and lowering Malondialdehyde (MDA) level (P < 0.05), 3,5-dicaffeoylquinic acid significantly mitigated the oxidative damage of AML-12 liver cells more than the other two phenolics. Our results demonstrated that 3,5-dicaffeoylquninic acid was the primary phenolic compounds in GJ that effectively reduced liver damage, providing a theoretical basis for the development of GJ as a potentially useful resource for hepatoprotective diet.

Impact of Gastrojejunostomy Anastomosis Diameter on Weight Loss Following Laparoscopic Gastric Bypass: A Systematic Review.

Laparoscopic Roux-en-Y gastric bypass (RYGB) is crucial for significant weight reduction and treating obesity-related issues. However, the impact of gastrojejunostomy (GJ) anastomosis diameter on weight loss remains unclear. We investigate this influence on post-RYGB weight loss outcomes. A systematic search was conducted. Six studies met the inclusion criteria, showing varied GJ diameters and follow-up durations (1-5 years). Smaller GJ diameters generally correlated with greater short-to-medium-term weight loss, with a threshold beyond which complications like stenosis increased. Studies had moderate-to-low bias risk, emphasizing the need for precise GJ area quantification post-operation. This review highlights a negative association between smaller GJ diameters and post-RYGB weight loss, advocating for standardized measurement techniques. Future research should explore intra-operative and AI-driven methods for optimizing GJ diameter determination.

The Connexin40A96S mutation from a patient with atrial fibrillation causes decreased atrial conduction velocities and sustained episodes of induced atrial fibrillation in mice.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and a major cause of stroke. In the mammalian heart the gap junction proteins connexin40 (Cx40) and connexin43 (Cx43) are strongly expressed in the atrial myocardium mediating effective propagation of electrical impulses. Different heterozygous mutations in the coding region for Cx40 were identified in patients with AF. We have generated transgenic Cx40A96S mice harboring one of these mutations, the loss-of-function Cx40A96S mutation, as a model for atrial fibrillation. Cx40A96S mice were characterized by immunochemical and electrophysiological analyses. Significantly reduced atrial conduction velocities and strongly prolonged episodes of atrial fibrillation were found after induction in Cx40A96S mice. Analyses of the gating properties of Cx40A96S channels in cultured HeLa cells also revealed significantly lower junctional conductance and enhanced sensitivity voltage gating of Cx40A96S in comparison to Cx40 wild-type gap junctions. This is caused by reduced open probabilities of Cx40A96S gap junction channels, while single channel conductance remained the same. Similar to the corresponding patient, heterozygous Cx40A96S mice revealed normal expression levels and localization of the Cx40 protein. We conclude that heterozygous Cx40A96S mice exhibit prolonged episodes of induced atrial fibrillation and severely reduced atrial conduction velocities similar to the corresponding human patient.

Comparison of primary jejunostomy tubes versus gastrojejunostomy tubes for percutaneous enteral nutrition.

PURPOSE: To evaluate technical success and long-term outcomes of percutaneous primary jejunostomy tubes for postpyloric enteral feeding compared with percutaneous gastrojejunostomy (GJ) tubes. MATERIALS AND METHODS: Over a 25-month interval, 41 consecutive patients (26 male; mean age, 55.9 y) underwent attempted fluoroscopy-guided direct percutaneous jejunostomy tube insertion. Insertions at previous jejunostomy tube sites were excluded. The comparison group consisted of all primary GJ tube insertions performed over a 12-month interval concomitant with the jejunostomy tube interval (N = 169; 105 male; mean age, 59.4 y). Procedural, radiologic, and clinical data were retrospectively reviewed. Intervention rates were expressed as events per 100 catheter-days. RESULTS: The technical success rate for percutaneous jejunostomy tube insertion was 96%, versus 93% for GJ tubes (P = .47). Mean fluoroscopy times were similar for jejunostomy and GJ tubes (9.8 vs 10.0 min, respectively; P value not significant). Jejunostomy tubes exhibited a lower rate of catheter dysfunction than GJ tubes, with catheter exchange rates of 0.24 versus 0.93, respectively, per 100 catheter-days (P = .045). GJ tube tip retraction into the stomach occurred in 9.5% of cases, at a rate of 0.21 per 100 catheter-days. Intervention rates related to leakage were 0.19 and 0.03 for jejunostomy and GJ tubes, respectively (P < .01). Jejunostomy and GJ tubes exhibited similar rates of catheter exchange for occlusion and replacement as a result of inadvertent removal. No major complications were encountered in either group. CONCLUSIONS: Percutaneous insertion of primary jejunostomy tubes demonstrated technical success and complication rates similar to those of GJ tubes. Jejunostomy tubes exhibited a lower dysfunction rate but a higher leakage rate compared with GJ tubes.

Cooperative cell-cell actin network remodeling to perform Gap junction endocytosis.

BACKGROUND: The endocytosis of Gap junction plaques (GJP) requires cytoskeletal forces to internalize such large membranous structures. Actin, which partners the connexin proteins constituting Gap junctions and is located close to Annular Gap Junctions (AGJ), could be actively involved in this physiological process. RESULTS: Electron Microscopy and Light Microscopy images, associated with time-lapse analysis and 3D reconstruction, used at high resolution and enhanced using ImageJ based software analysis, revealed that: i) actin cables, originating from Donor cells, insert on the edge of GJP and contribute to their invagination, giving rise to AGJ, whereas actin cables on the Acceptor cell side of the plaque are not modified; ii) actin cables from the Donor cell are continuous with the actin network present over the entire GJP surface. These actin cables fuse at a single point distant from the plaque, which then detaches itself from the membrane, condensing to form an actin mass during the final internalization process; iii) the Acceptor cell participates in the last step of the endocytic invagination process by forming an annular actin structure known as an actin ring. CONCLUSIONS: Together, these data suggest that the endocytosis of GJP is an example of a unique cooperative mechanism between the Donor (the traction of its actin cables) and the Acceptor cells (forming the actin ring).

RéSUMé: CONTEXTE: L'endocytose des plaques de jonctions communicantes ou jonctions gap (GJP) nécessite les forces du cytosquelette pour internaliser ces grandes structures membranaires. L'actine, partenaire des connexines, proteins constitutives des jonctions gap (Gj), localisée proche des jonctions gap annulaires (GJA), pourrait être impliquée dans ce processus physiologique. RéSULTATS: L' imagerie par microscopie optique et électronique, associées avec des analyses vidéo et des reconstructions en relief/3D, examinées à haute résolution et améliorées après traitement par des logiciels développés sous ImageJ, montrent que: i) des câbles d'actine, originaires des cellules donneuses, s'insèrent sur le bord des plaques jonctionnelles et facilitent leur invagination pour former les GJA tandis que les câbles d'actine des cellules receveuses ne sont pas modifies; ii) les câbles d'actine des cellules donneuses sont en continuité avec le réseau d'actine qui couvre la totalité de la surface de la plaque. De plus, ces câbles fusionnent en un point unique, à distance de la plaque, qui se détache de la région membranaire pour former une masse d'actine à la fin du processus d'endocytose; iii) la cellule receveuse participe à l'étape ultime du processus d'endocytose de la plaque en formant un anneau d'actine. CONCLUSIONS: L'ensemble de nos résultats montrent que l'endocytose des plaques jonctionnelles est un exemple de coopération unique entre la cellule donneuse (grâce à la traction des câbles d'actine) et la cellule receveuse (anneau d'actine).

Intussusception in an elderly female and its management: A case report and literature review.

Intussusception is the telescoping or invagination of the proximal part of the gastrointestinal tract into an adjacent section. It is rare in adults, accounting for 1% of adult bowel obstruction. Adult presentation of intussusception is variable, with nonspecific, vague symptoms like abdominal pain, nausea, vomiting, and rectal bleeding. Abdominal computed tomography (CT) scans have the highest sensitivity in the diagnosis of intussusception. The classical findings of intussusception are the target sign and mesenteric vessels lined within the bowel lumen. An abdominal CT scan can reveal a cloverleaf figuration, fluid-filled ileal loops, superior mesenteric venous (SMV) occlusion, and concerns about ongoing sealed perforation or fistulization. Our patient is an 86-year-old female who was diagnosed with a jejunal-jejunal long-segment intussusception, gastro-enteric fistula, and SMV occlusion with distal reconstitution. The patient responded well to conservative treatment and was discharged for follow-up.

Gardenia jasminoides Extract GJ-4 Alleviates Memory Deficiency of Vascular Dementia in Rats through PERK-Mediated Endoplasmic Reticulum Stress Pathway.

Endoplasmic reticulum stress (ERS) is involved in the pathological process of vascular dementia (VD). GJ-4 is extracted from Gardenia jasminoides J. Ellis and has been reported to have protective roles in ischemia-related brain damage. However, the role of GJ-4 in ERS has not been elucidated. We established a VD rat model through bilateral common carotid arteries occlusion (2-VO). The rats were intragastrically administrated with GJ-4 (10, 25, and 50[Formula: see text]mg/kg) and nimodipine (10[Formula: see text]mg/kg). Data from a Morris water maze test showed that GJ-4 could significantly alleviate learning and memory deficits in VD rats. Nissl and cleaved caspase-3 staining revealed that GJ-4 can inhibit apoptosis and thus exert a protective role in the brain of 2-VO rats. Western blot results suggested that GJ-4 significantly reduced ERS-related protein expression and inhibited apoptosis through suppression of the PERK/eIF2[Formula: see text]/ATF4/CHOP signaling pathway. For in vitro studies, the oxygen-glucose deprivation (OGD) SH-SY5Y model was employed. Western blot and Hoechst 33342/PI double staining were utilized to explore the effects of crocetin, the main active metabolite of GJ-4. Like GJ-4 in vivo, crocetin in vitro also decreased ERS-related protein expression and inhibited the activation of the PERK/eIF2[Formula: see text]/ATF4/CHOP signaling pathway. Thus, crocetin exerted similar protective roles on OGD challenged SH-SY5Y cells in vitro. In summary, GJ-4 and crocetin reduce the ERS in the brain of VD rats and SY5Y cells subjected to OGD and inhibit neuronal apoptosis through suppression of the PERK/eIF2[Formula: see text]/ATF4/CHOP pathway, suggesting that GJ-4 may be useful for the treatment of VD.