Minimally Invasive transCervical oEsophagectomy (MICE) for oesophageal cancer: prospective cohort study (IDEAL stage 2A).

BACKGROUND: Minimally invasive transcervical oesophagectomy is a surgical technique that offers radical oesophagectomy without the need for transthoracic access. The aim of this study was to evaluate the safety and feasibility of the minimally invasive transcervical oesophagectomy procedure and to report the refinement of this technique in a Western cohort. METHODS: A single-centre prospective cohort study was designed as an IDEAL stage 2A study. Patients with oesophageal cancer (cT1b-4a N0-3 M0) who were scheduled for oesophagectomy with curative intent were eligible for inclusion in the study. The main outcome parameter was the postoperative pulmonary complication rate and the secondary outcomes were the anastomotic leakage, recurrent laryngeal nerve palsy, and R0 resection rates, as well as the lymph node yield. RESULTS: In total, 75 patients underwent minimally invasive transcervical oesophagectomy between January 2021 and November 2023. Several modifications to the surgical technique were registered, evaluated, and implemented in the context of IDEAL stage 2A. A total of 12 patients (16%) had postoperative pulmonary complications, including pneumonia (4 patients) and pleural effusion with drainage or aspiration (8 patients). Recurrent laryngeal nerve palsy was observed in 33 of 75 patients (44%), with recovery in 30 of 33 patients (91%). A total of 5 of 75 patients (7%) had anastomotic leakage. The median number of resected lymph nodes was 29 (interquartile range 22-37) and the R0 resection rate was 96% (72 patients). CONCLUSION: Introducing minimally invasive transcervical oesophagectomy for oesophageal cancer in a Dutch institution is associated with a low rate of postoperative pulmonary complications and a high rate of temporary recurrent laryngeal nerve palsy.

Remarkable Improvement in Am3+ and Cm3+ Separation Using a Cooperative Counter Selectivity Strategy by a Combination of Branched Diglycolamides and Hydrophilic Polyaza-heterocycles.

Separation of Am3+ and Cm3+ is one of the most challenging problems in the back-end of the nuclear fuel cycle. In the present work, we exploited the cooperative effect of the opposite selectivity of hydrophobic branched DGA derivatives and hydrophobic N-donor heterocyclic ligands taken in two different phases to achieve improved separation behavior. A systematic study was performed using a series of DGA derivatives to understand the effect and the position of branching in the alkyl chains on the separation behavior of Am3+ and Cm3+. A separation factor (S.F.) value as high as 10 for Cm3+ over Am3+ was obtained in the case of TiBDGA (N,N,N',N'-tetra-iso-butyl diglycolamide) using SO3PhBTPhen ((phenanthroline-2,9-diyl)-1,2,4-triazine-5,5,6,6-tetrayltetrabenzenesulfonic acid) as the aqueous complexant, which is the highest reported value so far for the ligand-based separation of Am3+ and Cm3+ without involving any oxidation or reduction step. The high selectivity favoring Cm3+ ion extraction in the case of this DGA derivative is also explained with the help of computational studies.

Understanding the Complexation of Alkyl-Substituted Nitrilotriacetamides with Uranium: A Study by Absorption Spectroscopy and Microcalorimetry.

Complexation thermodynamics of UO22+ ions with a series of alkyl-substituted nitrilotriacetamides (NTA) was investigated by absorption spectroscopy and microcalorimetry. The hexamethyl derivative of NTA (HMNTA) forms the weakest two successive complexes with UO22+ ions with stability constants of log ß11 = 3.5 ± 0.1 and log ß12 = 6.1 ± 0.1. The formation constant values increased linearly with increasing alkyl chain length of the substituents from hexamethyl NTA to hexabutyl NTA (HBNTA) and to hexahexyl NTA (HHNTA). The complexation with each ligand was both enthalpy and entropy driven with exothermic enthalpy changes of ΔH11 = -14.7 ± 1.0 kJ/mol, ΔH12 = -10.2 ± 0.8 kJ/mol for HMNTA, ΔH11 = -19.2 ± 1.2 kJ/mol, ΔH12 = -16.4 ± 1.1 kJ/mol for HBNTA, and ΔH11 = -21.3 ± 1.4 kJ/mol, ΔH12 = -19.4 ± 2.3 kJ/mol for HHNTA. Similarly, the positive entropy changes with each ligand were ΔS11 = 18.1 ± 2.7 J/mol/K, ΔS12 = 82.9 ± 3.8 J/mol/K for HMNTA, ΔS11 = 14.4 ± 1.2 J/mol/K, ΔS12 = 87.2 ± 4.2 J/mol/K for HBNTA, and ΔS11 = 16.1 ± 2.4 J/mol/K, ΔS12 = 92.6 ± 3.1 J/mol/K for HHNTA. Structural features of the complex suggest the participation of two ligands coordinating in a bidentate mode via the carbonyl oxygens. The [UO2L2]2+ complexes appear to be noncentrosymmetric with two ligands and one water molecule occupying the equatorial plane of the dioxo uranyl cation. The structure of the complex was confirmed by 1H NMR titration, EXAFS measurements, and DFT calculations.

Contrasting consequences of podocyte insulin-like growth factor 1 receptor inhibition.

Insulin signaling to the glomerular podocyte via the insulin receptor (IR) is critical for kidney function. In this study we show that near-complete knockout of the closely related insulin-like growth factor 1 receptor (IGF1R) in podocytes is detrimental, resulting in albuminuria in vivo and podocyte cell death in vitro. In contrast, partial podocyte IGF1R knockdown confers protection against doxorubicin-induced podocyte injury. Proteomic analysis of cultured podocytes revealed that while near-complete loss of podocyte IGF1R results in the downregulation of mitochondrial respiratory complex I and DNA damage repair proteins, partial IGF1R inhibition promotes respiratory complex expression. This suggests that altered mitochondrial function and resistance to podocyte stress depends on the level of IGF1R suppression, the latter determining whether receptor inhibition is protective or detrimental. Our work suggests that the partial suppression of podocyte IGF1R could have therapeutic benefits in treating albuminuric kidney disease.

Understanding the Interaction of Uranyl Cation with Two C-Pivot Tripodal Amides: Synthesis, Complexation, Microcalorimetry, and DFT Studies.

Complexation of uranyl ions with two structurally related C-pivotal tripodal amides with varying spacer lengths, synthesized for the first time, was studied by optical spectroscopy. In the tripodal amides, the coordination was through the carbonyl O atoms where the carbonyl groups were away from the central C-atom by three spacer atoms (LI) and four spacer atoms (LII), respectively. Increasing the spacer atoms going from LI to LII favors the complexation with the linear uranyl cations and results in stronger complex formation. The complexation heat between the uranyl cations and the two amide ligands was directly measured by microcalorimetric titrations. The complexation with both the ligands was driven by exothermic enthalpy and positive entropy changes. Formation of the complex proceeded by the replacement of water molecules from the primary coordination sphere of the uranyl cation. Both ligands formed bisolvated (ML2-type) complexes in which one unit of the ligand binds in a monodentate manner and the other in a bidentate mode. Density functional theory calculations further supported our experimental observations.

Efficient actinide sequestration with ionic liquid-based extraction chromatography resins containing Aza-crown ether functionalized diglycolamides.

Two new extraction chromatographic resins (ECRs) were prepared by impregnating two exotic diglycolamide (DGA) ligands (having three or four DGA moieties tethered to aza-crown ether scaffolds) dissolved in an ionic liquid onto an inert solid support. A room temperature ionic liquid (RTIL) was used for enhancing the performance of the ECRs. The ECR containing triaza-9-crown-3 functionalized with three DGA moieties (TAM-3-DGA), and tetraaza-12-crown-4 tethered with four DGA arms (TAM-4-DGA) were evaluated for the separation of Am3+ and Pu4+from nitric acid solutions. The resin capacity for Eu3+ was 9.52 mg/g and 7.24 mg/g for TAM-3-DGA and TAM-4-DGA resins, respectively. Similarly, the resin capacity for Pu4+was 7.44 mg/g and 5.72 mg/g for TAM-3-DGA and TAM-4-DGA resins, respectively. These maximum loading values corresponded to the formation of a 1:1 metal/ligand complex for the Eu3+ ion and a 1:2 metal/ligand complex for the Pu4+ ion. The sorption of Eu3+and Pu4+on the resins followed a chemisorption phenomenon on both resins. The sorbed Eu3+and Pu4+ions from the resin phase could be efficiently desorbed with complexing ligands such as guanidine carbonate/HEDTA and oxalic acid, respectively.

Value of routine follow-up for recurrence detection after treatment with curative intent for laryngeal squamous cell carcinoma.

INTRODUCTION: The benefits of routine follow-up after treatment of primary laryngeal squamous cell carcinoma (LSCC) remain disputed. Guidelines worldwide are consensus-based, and evidence for specific subgroups is lacking. This study evaluates routine LSCC follow-up including flexible endoscopy for detecting locoregional recurrence (LRR). METHODS: A retrospective cohort of 413 LSCC patients treated between 2006 and 2012 was analysed. The cumulative risk of LRR was calculated. Routine follow-up was evaluated by follow-up visit (routine or interval) at which LRR was detected, LRR treatment intent, and overall survival (OS). Analyses were stratified by early (I-II) and advanced (III-IV) TNM-stage. RESULTS: There were 263 (64 %) patients with early-stage and 132 (32 %) patients with advanced-stage LSCC. One-, two- and five-year cumulative risks for LRR after early-stage LSCC were 8 %, 18 %, and 26 %. For advanced-stage LSCC, cumulative risks of LRR were 20 %, 30 %, and 35 %. Of all 69 LRRs after early-stage LSCC, 72 % were routine-detected, 81 % were symptomatic, and 90 % received curative-intent treatment. Of all 45 LRRs following advanced-stage LSCC, 42 % were routine-detected, 84 % were symptomatic, and 62 % received curative-intent treatment. Five-year OS of early-stage LSCC with routine-detected LRR was 70 %, and 72 % for interval-detection (log-rank-p = 0.91). Five-year OS of advanced-stage LSCC with routine-detected LRR was 37 %, and 18 % for interval-detection (log-rank-p = 0.06). CONCLUSIONS: Routine follow-up for detecting asymptomatic recurrences seems redundant for early-stage LSCC. After advanced-stage LSCC, no asymptomatic recurrences were detected beyond one year posttreatment despite regular follow-up. Emphasis should be on other follow-up aspects, such as psychosocial support, especially after one year posttreatment.

Validation of a new optical diagnosis training module to improve dysplasia characterization in inflammatory bowel disease: a multicenter international study.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) increases risk of dysplasia and colorectal cancer. Advanced endoscopic techniques allow for the detection and characterization of IBD dysplastic lesions, but specialized training is not widely available. We aimed to develop and validate an online training platform to improve the detection and characterization of colonic lesions in IBD: OPtical diagnosis Training to Improve dysplasia Characterization in Inflammatory Bowel Disease (OPTIC-IBD). METHODS: We designed a web-based learning module that includes surveillance principles, optical diagnostic methods, approach to characterization, and classifications of colonic lesions using still images and videos. We invited gastroenterologists from Canada, Italy, and the United Kingdom with a wide range of experience. Participants reviewed 24 educational videos of IBD colonic lesions, predicted histology, and rated their confidence. The primary endpoint was to improve accuracy in detecting dysplastic lesions after training on the platform. Furthermore, participants were randomized 1:1 to get additional training or not, with a final assessment occurring after 60 days. Diagnostic performance for dysplasia and rater confidence were measured. RESULTS: A total of 117 participants completed the study and were assessed for the primary endpoint. Diagnostic accuracy improved from 70.8% to 75.0% (P = .002) after training, with the greatest improvements seen in less experienced endoscopists. Improvements in both accuracy and confidence were sustained after 2 months of assessment, although the group randomized to receive additional training did not improve further. Similarly, participants' confidence in characterizing lesions significantly improved between before and after the course (P < .001), and it was sustained after 2 months of assessment. CONCLUSIONS: The OPTIC-IBD training module demonstrated that an online platform could improve participants' accuracy and confidence in the optical diagnosis of dysplasia in patients with IBD. The training platform can be widely available and improve endoscopic care for people with IBD. (Clinical trial registration number: NCT04924543.).

Shiga toxin targets the podocyte causing hemolytic uremic syndrome through endothelial complement activation.

BACKGROUND: Shiga toxin (Stx)-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is the leading cause of acute kidney injury in children, with an associated mortality of up to 5%. The mechanisms underlying STEC-HUS and why the glomerular microvasculature is so susceptible to injury following systemic Stx infection are unclear. METHODS: Transgenic mice were engineered to express the Stx receptor (Gb3) exclusively in their kidney podocytes (Pod-Gb3) and challenged with systemic Stx. Human glomerular cell models and kidney biopsies from patients with STEC-HUS were also studied. FINDINGS: Stx-challenged Pod-Gb3 mice developed STEC-HUS. This was mediated by a reduction in podocyte vascular endothelial growth factor A (VEGF-A), which led to loss of glomerular endothelial cell (GEnC) glycocalyx, a reduction in GEnC inhibitory complement factor H binding, and local activation of the complement pathway. Early therapeutic inhibition of the terminal complement pathway with a C5 inhibitor rescued this podocyte-driven, Stx-induced HUS phenotype. CONCLUSIONS: This study potentially explains why systemic Stx exposure targets the glomerulus and supports the early use of terminal complement pathway inhibition in this devastating disease. FUNDING: This work was supported by the UK Medical Research Council (MRC) (grant nos. G0901987 and MR/K010492/1) and Kidney Research UK (grant nos. TF_007_20151127, RP42/2012, and SP/FSGS1/2013). The Mary Lyon Center is part of the MRC Harwell Institute and is funded by the MRC (A410).

Bedside Intestinal Ultrasound Performed in an Inflammatory Bowel Disease Urgent Assessment Clinic Improves Clinical Decision-Making and Resource Utilization.

Background: Patients with inflammatory bowel disease (IBD) require accessible, timely, and noninvasive strategies to monitor disease. The aim was to assess the integration of intestinal ultrasound (IUS) on decision-making and endoscopy utilization in a standardized care pathway. Methods: This prospective, multicenter, international, observational cohort study included patients seen within a centralized model for IBD care was conducted during the COVID pandemic. Patients were evaluated with IUS alone or in combination with an in-clinic, unsedated sigmoidoscopy. Demographic, clinical, laboratory, and imaging data, clinical decisions, and need for urgent endoscopy, hospitalization, and surgeries were recorded. Results: Of the 158 patients included, the majority had an established diagnosis of Crohn's disease (n = 123, 78%), and 47% (n = 75) of patients were on biologic therapy. IUS identified active inflammation in 65% (n = 102) of patients, and strictures in 14% (n = 22). Fecal calprotectin levels correlated with inflammation detected on IUS (median of 50 µg/g [Q1-Q3: 26-107 µg/g] without inflammation and 270 µg/g [Q1-Q3: 61-556 µg/g] with inflammation; p = 0.0271). In the majority of patients, clinical assessment with IUS led to an acute change in IBD-specific medications (57%, n = 90) and avoided or delayed the need for urgent endoscopy (85%, n = 134). Four patients were referred for urgent surgical consultation. Conclusions: Point-of-care IUS used in a flare clinic pathway is a useful strategy to improve effective IBD care delivery and to assist in therapeutic management decisions, in many cases avoiding the acute need for endoscopy.

Outcome monitoring and risk stratification after cardiac procedure in neonates, infants, children and young adults born with congenital heart disease: protocol for a multicentre prospective cohort study (Children OMACp).

INTRODUCTION: Congenital heart disease (CHD) represents the most common birth defect, affecting from 0.4% to 1.2% of children born in developed countries. The survival of these patients has increased significantly, but CHD remains one of the major causes of neonatal and childhood death. The aetiology of CHD is complex, with some evidence of both genetic and environmental causes. However, there is still lack of knowledge regarding modifiable risk factors and molecular and genetic mechanisms underlying the development of CHD. This study aims to develop a prospective cohort of patients undergoing cardiac procedures that will bring together routinely collected clinical data and biological samples from patients and their biological mothers, in order to investigate risk factors and predictors of postoperative-outcomes, as well as better understanding the effect of the surgical intervention on the early and long-term outcomes. METHODS AND ANALYSIS: Children OMACp (OMACp, outcome monitoring after cardiac procedure in congenital heart disease) is a multicentre, prospective cohort study recruiting children with CHD undergoing a cardiac procedure. The study aims to recruit 3000 participants over 5 years (2019-2024) across multiple UK sites. Routine clinical data will be collected, as well as participant questionnaires collecting sociodemographic, NHS resource use and quality of life data. Biological samples (blood, urine and surgical waste tissue from patients, and blood and urine samples from biological mothers) will be collected where consent has been obtained. Follow-up outcome and questionnaire data will be collected for 5 years. ETHICS AND DISSEMINATION: The study was approved by the London-Brent Research Ethics Committee on 30 July 2019 (19/SW/0113). Participants (or their parent/guardian if under 16 years of age) must provide informed consent prior to being recruited into the study. Mothers who wish to take part must also provide informed consent prior to being recruited. The study is sponsored by University Hospitals Bristol and Weston Foundation Trust and is managed by the University of Bristol. Children OMACp is adopted onto the National Institute for Health Research Clinical Research Network portfolio. Findings will be disseminated through peer-reviewed publications, presentation at conference, meetings and through patient organisations and newsletters. TRIAL REGISTRATION NUMBER: ISRCTN17650644.

Adverse Events and Serological Responses After SARS-CoV-2 Vaccination in Individuals With Inflammatory Bowel Disease.

INTRODUCTION: We determined adverse events after 4 doses of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine in those with inflammatory bowel disease (IBD), associations between antibodies and injection site reactions (ISR), and risk of IBD flare. METHODS: Individuals with IBD were interviewed for adverse events to SARS-CoV-2 vaccine. Multivariable linear regression assessed the association between antibody titers and ISR. RESULTS: Severe adverse events occurred in 0.03%. ISR were significantly associated with antibody levels after the fourth dose (geometric mean ratio = 2.56; 95% confidence interval 1.18-5.57). No cases of IBD flare occurred. DISCUSSION: SARS-CoV-2 vaccines are safe for those with IBD. ISR after the fourth dose may indicate increased antibodies.

Weighted Gene Co-Expression Network Analysis Identifies a Functional Guild and Metabolite Cluster Mediating the Relationship between Mucosal Inflammation and Adherence to the Mediterranean Diet in Ulcerative Colitis.

Diet influences the pathogenesis and clinical course of inflammatory bowel disease (IBD). The Mediterranean diet (MD) is linked to reductions in inflammatory biomarkers and alterations in microbial taxa and metabolites associated with health. We aimed to identify features of the gut microbiome that mediate the relationship between the MD and fecal calprotectin (FCP) in ulcerative colitis (UC). Weighted gene co-expression network analysis (WGCNA) was used to identify modules of co-abundant microbial taxa and metabolites correlated with the MD and FCP. The features considered were gut microbial taxa, serum metabolites, dietary components, short-chain fatty acid and bile acid profiles in participants that experienced an increase (n = 13) or decrease in FCP (n = 16) over eight weeks. WGCNA revealed ten modules containing sixteen key features that acted as key mediators between the MD and FCP. Three taxa (Faecalibacterium prausnitzii, Dorea longicatena, Roseburia inulinivorans) and a cluster of four metabolites (benzyl alcohol, 3-hydroxyphenylacetate, 3-4-hydroxyphenylacetate and phenylacetate) demonstrated a strong mediating effect (ACME: -1.23, p = 0.004). This study identified a novel association between diet, inflammation and the gut microbiome, providing new insights into the underlying mechanisms of how a MD may influence IBD. See clinicaltrials.gov (NCT04474561).

Innovative Care for Inflammatory Bowel Disease Patients during the COVID-19 Pandemic: Use of Bedside Intestinal Ultrasound to Optimize Management.

Background: The COVID-19 pandemic caused by SARS-CoV-2 has reduced access to endoscopy and imaging. Safe alternatives, available at the bedside, are needed for accurate, non-invasive strategies to evaluate disease activity. The aim of this study is to establish the impact of clinic-based bedside intestinal ultrasound (IUS) on decision making, reduction in reliance on endoscopy and short-term healthcare utilization. Methods: We conducted a prospective observational evaluation during the COVID-19 pandemic, of the impact of a regional comprehensive care pathway to manage IBD patients consecutively recruited with acute symptoms, or suspected new diagnosis of IBD. Clinic-based access to sigmoidoscopy and bedside intestinal ultrasound were evaluated, used to direct clinical care and avoid hospitalization or hospital-based endoscopy. Results: A total of 72 patients were seen between March 15 and June 30, 2020. Of these, 57% (41/72) were female, 64% had Crohn's disease (46/72) with 14% (10/72) presenting with symptoms requiring investigation, of which 5 new cases of IBD were identified (50%). Immediate access to ultrasound and sigmoidoscopy led to meaningful changes in management in 80.5% (58/72) of patients. Active inflammation was detected by IUS alone (72.5%, 29/40) or in combination with in-clinic sigmoidoscopy (78%, 18/23) or sigmoidoscopy alone (78% 7/9). Six patients were referred to colorectal surgery for urgent surgical intervention including two patients admitted directly. Conclusion: Implementation of IUS as part of a clinical care pathway during the COVID-19 pandemic is a useful strategy to enhance care delivery and improve clinical decisions, while sparing other important acute care resources.

An in vitro approach to understand contribution of kidney cells to human urinary extracellular vesicles.

Extracellular vesicles (EV) are membranous particles secreted by all cells and found in body fluids. Established EV contents include a variety of RNA species, proteins, lipids and metabolites that are considered to reflect the physiological status of their parental cells. However, to date, little is known about cell-type enriched EV cargo in complex EV mixtures, especially in urine. To test whether EV secretion from distinct human kidney cells in culture differ and can recapitulate findings in normal urine, we comprehensively analysed EV components, (particularly miRNAs, long RNAs and protein) from conditionally immortalised human kidney cell lines (podocyte, glomerular endothelial, mesangial and proximal tubular cells) and compared to EV secreted in human urine. EV from cell culture media derived from immortalised kidney cells were isolated by hydrostatic filtration dialysis (HFD) and characterised by electron microscopy (EM), nanoparticle tracking analysis (NTA) and Western blotting (WB). RNA was isolated from EV and subjected to miRNA and RNA sequencing and proteins were profiled by tandem mass tag proteomics. Representative sets of EV miRNAs, RNAs and proteins were detected in each cell type and compared to human urinary EV isolates (uEV), EV cargo database, kidney biopsy bulk RNA sequencing and proteomics, and single-cell transcriptomics. This revealed that a high proportion of the in vitro EV signatures were also found in in vivo datasets. Thus, highlighting the robustness of our in vitro model and showing that this approach enables the dissection of cell type specific EV cargo in biofluids and the potential identification of cell-type specific EV biomarkers of kidney disease.

Direct age constraints on the magnetism of Jack Hills zircon.

A potential record of Earth's magnetic field going back 4.2 billion years (Ga) ago is carried by magnetite inclusions in zircon grains from the Jack Hills. This magnetite may be secondary in nature, however, meaning that the magnetic record is much younger than the zircon crystallization age. Here, we use atom probe tomography to show that Pb-bearing nanoclusters in magnetite-bearing Jack Hills zircons formed during two discrete events at 3.4 and <2 Ga. The older population of clusters contains no detectable Fe, whereas roughly half of the younger population of clusters is Fe bearing. This result shows that the Fe required to form secondary magnetite entered the zircon sometime after 3.4 Ga and that remobilization of Pb and Fe during an annealing event occurred more than 1 Ga after deposition of the Jack Hills sediment at 3 Ga. The ability to date Fe mobility linked to secondary magnetite formation provides new possibilities to improve our knowledge of the Archean geodynamo.

Multimodal Brain MRI of Deep Gray Matter Changes Associated With Inflammatory Bowel Disease.

BACKGROUND: Behavioral symptoms, including mood disorders, substantially impact the quality of life of patients with inflammatory bowel disease (IBD), even when clinical remission is achieved. Here, we used multimodal magnetic resonance imaging (MRI) to determine if IBD is associated with changes in the structure and function of deep gray matter brain regions that regulate and integrate emotional, cognitive, and stress responses. METHODS: Thirty-five patients with ulcerative colitis (UC) or Crohn's disease (CD) and 32 healthy controls underwent 3 Tesla MRIs to assess volume, neural activity, functional connection strength (connectivity), inflammation, and neurodegeneration of key deep gray matter brain regions (thalamus, caudate, pallidum, putamen, amygdala, hippocampus, and hypothalamus) involved in emotional, cognitive and stress processing. Associations with sex, presence of pain, disease activity, and C-reactive protein (CRP) concentration were examined. RESULTS: Significantly increased activity and functional connectivity were observed in cognitive and emotional processing brain regions, including parts of the limbic system, basal ganglia, and hypothalamus of IBD patients compared with healthy controls. Inflammatory bowel disease patients exhibited significantly increased volumes of the amygdala and hypothalamus, as well as evidence of neurodegeneration in the putamen and pallidum. Hippocampal neural activity was increased in IBD patients with active disease. The volume of the thalamus was positively correlated with CRP concentration and was increased in females experiencing pain. CONCLUSIONS: Patients with IBD exhibit functional and structural changes in the limbic and striatal systems. These changes may be targets for assessing or predicting the response to therapeutic interventions aimed at improving comorbid emotional and cognitive symptoms.

Magnetic resonance imaging revealed structural and functional changes within the brains of inflammatory bowel disease patients, in regions known to be involved in processing brain signals associated with behavioral symptoms, anxiety, pain, stress, and cognitive deficits.

Aggregation Behavior of Nitrilotriacetamide (NTAmide) Ligands in Thorium(IV) Extraction from Acidic Medium: Small-Angle Neutron Scattering, Fourier Transform Infrared, and Theoretical Studies.

Two tripodal amides obtained from nitrilotriacetic acid with n-butyl and n-octyl alkyl chains (HBNTA(LI) and HONTA(LII), respectively) were studied for the extraction of Th(IV) ions from nitric acid medium. The effect of the diluent medium, i.e., n-dodecane alone and a mixture of n-dodecane and 1-decanol, onto aggregate formation were investigated using small angle neutron scattering (SANS) studies. In addition, the influence of the ligand structure, nitric acid, and Th(IV) loading onto ligand aggregation and third-phase formation tendency was discussed.The LI/LII exist as monomers (aggregarte radius for LI: 6.0 Å; LII:7.4 Å) in the presence of 1-decanol, whereas LII forms dimers (aggregarte radius for LII:9.3 Å; LI does not dissolve in n-dodecane) in the absence of 1-decanol. The aggregation number increases for both the ligands after HNO3 and Th(IV) loading. The maximum organic concentration (0.050 ± 0.004 M) of Th(IV) was reached without third-phase formation for 0.1 M LI/LII dissolved in 20% isodecanol +80% n-dodecane. The interaction of 1-decanol with LII and HNO3/Th(IV) with amidic oxygens of LI/LII results in shift of carbonyl stretching frequency, as shown by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) studies. The structural and bonding information of the Th-LI/LII complex were derived from the density functional theoretical (DFT) studies. The molecular dynamics (MD) simulations suggested that the aggregation behavior of the ligand in the present system is governed by the population of hydrogen bonds by phase modifier around the ligand molecules. Although the theoretical studies suggested higher Gibbs free energy of complexation for Th4+ ions with LI than LII, the extraction was found to be higher with the latter, possibly due to the higher lipophilicity and solubility of the Th-LII aggregate in the nonpolar media.