BackgroundInflammatory bowel diseases (IBD) are a group of complex and multifactorial disorders with unknown etiology. Chronic intestinal inflammation develops against resident intestinal bacteria in genetically susceptible hosts. We hypothesized that host intestinal immunoglobulin (Ig) G can be used to identify bacteria involved in IBD pathogenesis.ResultsIgG-bound and -unbound microorganisms were collected from 32 pediatric terminal ileum aspirate washes during colonoscopy [non-IBD (n = 10), Crohn disease (n = 15), and ulcerative colitis (n = 7)], and composition was assessed using the Illumina MiSeq platform. In vitro analysis of invasive capacity was evaluated by fluorescence in situ hybridization and gentamicin invasion assay; immune activation was measured by qPCR. Despite considerable inter-individual variations, IgG binding favored specific and unique mucosa-associated species in pediatric IBD patients. Burkholderia cepacia, Flavonifractor plautii, and Rumminococcus sp. demonstrated increased IgG binding, while Pseudomonas ST29 demonstrated reduced IgG binding, in IBD. In vitro validation confirmed that B. cepacia, F. plautii, and Rumminococcus display invasive potential while Pseudomonas protogens did not.ConclusionUsing IgG as a marker of pathobionts in larger patient cohorts to identify microbes and elucidate their role in IBD pathogenesis will potentially underpin new strategies to facilitate development of novel, targeted diagnostic, and therapeutic approaches. Interestingly, this method can be used beyond the scope of this manuscript to evaluate altered gut pathobionts in a number of diseases associated with altered microbiota including arthritis, obesity, diabetes mellitus, alcoholic liver disease, cirrhosis, metabolic syndrome, and carcinomas.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0604-3) contains supplementary material, which is available to authorized users.

These findings suggest an underlying defect in the UC-afflicted intestinal tract even in the absence of inflammation, implicating barrier and microbial changes as primary abnormalities in UC that may play a causative role in disease development.

Nuclear targeting of stanniocalcin to mammary gland alveolar cells during pregnancy and lactation. Am J Physiol Endocrinol Metab 289: E634 -E642, 2005; doi:10.1152/ajpendo.00098.2005.-In most mammalian tissues, the stanniocalcin-1 gene (STC-1) produces a 50-kDa polypeptide hormone known as STC50. Within the ovaries, however, the STC-1 gene generates three higher-molecular-mass variants known as big STC. Big STC is targeted locally to corpus luteal cells to block progesterone release. During pregnancy and lactation, however, ovarian big STC production increases markedly, and the hormone is released into the serum. During lactation, this increase in hormone production is dependent on a suckling stimulus, suggesting that ovarian big STC may have regulatory effects on the lactating mammary gland. In this report, we have addressed this possibility. Our results revealed that virgin mammary tissue contained large numbers of membrane-and mitochondrial-associated STC receptors. However, as pregnancy progressed into lactation, there was a decline in receptor densities on both organelles and a corresponding rise in nuclear receptor density, most of which were on milk-producing, alveolar cells. This was accompanied by nuclear sequestration of the ligand. Sequestered STC resolved as one ϳ135-kDa band in the native state and therefore had the appearance of a big STC variant. However, chemical reduction collapsed this one band into six closely spaced, lower-molecular-mass species (28 -41 kDa). Mammary gland STC production also underwent a dramatic shift during pregnancy and lactation. High levels of STC gene expression were observed in mammary tissue from virgin and pregnant rats. However, gene expression then fell to nearly undetectable levels during lactation, coinciding with the rise in nuclear targeting. These findings have thus shown that the mammary glands are indeed targeted by STC, even in the virgin state. They have further shown that there are marked changes in this targeting pathway during pregnancy and lactation, accompanied by a switch in ligand source (endogenous to exogenous). They also represent the first example of nuclear targeting by STC.

IntroductionElectronic consultation (eConsult)—provider-to-provider electronic asynchronous exchanges of patient health information at a distance—is emerging as a potential tool to improve the interface between primary care providers and specialists. Despite growing evidence that eConsult has clinical benefits, it is not widely adopted. We investigated factors influencing the adoption and implementation of eConsult services.MethodsWe applied established methods to guide the review, and the recently published Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews to report our findings. We searched five electronic databases and the grey literature for relevant studies. Two reviewers independently screened titles and full texts to identify studies that reported barriers to and/or facilitators of eConsult (asynchronous (store-and-forward) use of telemedicine to exchange patient health information between two providers (primary and secondary) at a distance using secure infrastructure). We extracted data on study characteristics and key barriers and facilitators were analysed thematically and classified using the Quadruple Aim framework taxonomy. No date or language restrictions were applied.ResultsAmong the 2579 publications retrieved, 130 studies met eligibility for the review. We identified and summarised key barriers to and facilitators of eConsult adoption and implementation across four domains: provider, patient, healthcare system and cost. Key barriers were increased workload for providers, privacy concerns and insufficient reimbursement for providers. Main facilitators were remote residence location, timely responses from specialists, utilisation of referral coordinators, addressing medicolegal concerns and incentives for providers to use eConsult.ConclusionThere are multiple barriers to and facilitators of eConsult adoption across the domains of Quadruple Aim framework. Our findings will inform the development of practice tools to support the wider adoption and scalability of eConsult implementation.

Inflammatory bowel diseases (IBD), encompassing both Crohn Disease (CD) and ulcerative colitis (UC) are globally prevalent diseases, impacting children of all ages. The hallmark of IBD is a perturbed immune system that leads to continuous inflammation in the gut and challenges optimal treatment. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ), a nuclear transcription factor, plays a major role in gut homeostasis and contributes significantly toward a balanced, homeostatic immune system. Dysregulation in the NF-κβ pathway and factors that regulate it lead to a state of uncontrolled inflammation and altered immunity, as typically observed in IBD. Levels of proinflammatory cytokines that are regulated through NF-κβ are increased in both CD and UC. Genes known to activate NF-κβ, such as, Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and Interleukin 23 (IL-23), are associated with IBD. Factors involved in inhibition of NF-κβ, such as A20 and TOLLIP, are also affected in IBD, resulting in failed inflammation suppression/regulation. NOD-2 and A20 have specifically been found to be strongly associated with pediatric IBD. Gut commensals are known to exert anti-inflammatory activities toward NF-κβ and can have a potential role in attenuating inflammation that likely occurs due to microbial dysbiosis in IBD. Failure to terminate/downregulate NF-κβ signaling results in chronic inflammation in IBD. Well-regulated control of inflammation in children with IBD can help better control the disease and suppress immune responses. Better understanding of factors that control NF-κβ can potentially lead toward discovering targeted therapeutic interventions for IBD. Suppression of NF-κβ can be achieved through many modalities including anti-sense oligonucleotides (ASOs), siRNA (small interfering RNA), factors regulating NF-κβ, and microbes. This review focuses on the role of NF-κβ, especially in pediatric IBD, and potential therapeutic venues for attenuating NF-κβ-induced inflammation.

Duodenal epithelial gaps are increased in pediatric patients with IBD (including UC) but are unrelated to inflammation. This suggests that altered epithelial barrier is an important systemic feature of pediatric IBD and is not only secondary to inflammation.

Background: Hypertension is a major cause of cardiovascular disease, chronic kidney disease (CKD), and death. Several studies have demonstrated the efficacy of home blood pressure telemonitoring (HBPT) for blood pressure (BP) control and outcomes, but the effects of this intervention remain unclear in patients with CKD. Objective: To determine the impact of HBPT on cardiovascular–related and kidney disease–related outcomes in patients with CKD. Design: Systematic review and meta-analysis. Setting: All studies that met our criteria regardless of country of origin. Participants: Patients with chronic kidney disease included in studies using HBPT for BP assessment and control. Measurements: Descriptive and quantitative analysis of our primary and secondary outcomes. Methods: We searched MEDLINE, Embase, CINAHL Plus, PsycINFO, Cochrane CENTRAL, Web of Science, and gray literature from inception for observational and randomized controlled studies in nondialysis (ND) CKD using HBPT for BP control. We selected studies that used HBPT as intervention (with or without a control arm) for BP control in ND-CKD populations. The primary outcome was change in mean systolic BP (SBP) and mean diastolic BP (DBP). Results: We selected 7 studies from 1669 articles that were initially identified. Overall, pooled estimates in the mean difference (MD) for SBP and DBP were −8.8 mm Hg; 95% confidence interval (CI): −16.2 to −1.4; P = .02 and −2.4 mm Hg; 95% CI: −3.8 to −1.0; P < .001, respectively. For studies comparing intervention with usual care (UC), pooled estimate in MD for SBP was −8.0 mm Hg ( P = .02) with no significant reduction for DBP (−2.6 mm Hg; P = .18). In studies without a UC arm, both SBP and DBP were not significantly reduced ( P > .05). The pooled estimate in MD for estimated glomerular filtration rate showed a significant improvement (5.4 mL/min/1.73 m2; P < .001). Limitations: Heterogeneity and few available studies for inclusion limited our ability to identify a robust link between HBPT use and BP and kidney function improvement. Conclusion: Home blood pressure telemonitoring is associated with mild lowering of BP and moderately improved kidney function in patients with CKD. However, larger studies with improved designs and prolonged interventions are still needed to assess the effects of HBPT on patients’ outcomes. PROSPERO registration ID CRD42020190705

PurposeA significant feature of pediatric inflammatory bowel diseases (IBD), which include Crohn disease (CD), and ulcerative colitis (UC), is failure to suppress inflammation. The inability to regulate inflammation renders a major challenge toward establishing effective treatments in IBD. Nuclear factor kappa-light-chain-enhancer of activated B-cells-induced inflammation is inhibited by A20 through interactions with TAX1BP1 (Tax1-binding protein 1) and A20-binding inhibitor of NF-κβ activation (ABIN)-1 (A20 binding and inhibitor of NF-κβ) and upon phosphorylation by inhibitor of nuclear factor kappa-β kinase subunit beta (IKKβ), which stabilizes it. We hypothesized that dysregulation of A20 is an important factor in uncontrolled inflammation in pediatric IBD.Patients and methodsGene expression of A20, IKKβ, ABIN-1, TAX1BP1, A20 protein, cytokine levels, and A20 phosphorylation was analyzed in the terminal ileum (TI) of 39 patients (14 non-IBD, 15 CD, and 10 UC). A20 expression and protein in T-84 cells and ex vivo biopsies of patients were measured after treatment with Escherichia coli strains or tumor necrosis factor (TNF)-α.ResultsTNF-α levels and A20 expression were increased in the TI of CD patients. A20 protein levels and ABIN-1 expression were low, TAX1BP1 expression was high, and IKKβ was unchanged. A20 expression positively correlated with biopsy TNF-α levels and inflammatory markers in CD patients. A20 phosphorylation appeared lower in CD patients. A20 expression in TI biopsies from CD patients and T84 cells was triggered with E. coli, strain LF82, while A20 protein levels remained unchanged.ConclusionWe describe a potential mechanism related to failure of A20 to suppress inflammation in CD, characterized by high A20 expression and low A20 protein levels. The dysregulation of A20 is potentially due to alterations in ABIN-1, and infection with E. coli strain LF82 could affect the function and stability of A20. Our study signifies an important finding in A20 regulation in IBD, which prevents it from suppressing inflammation.