ObjectiveType 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota–immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT).DesignPatients with recent-onset (<6 weeks) T1D (18–30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition.ResultsStimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal Prevotella was inversely related to residual beta cell function (r=−0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal Desulfovibrio piger and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics.ConclusionFMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D.Trial registration numberNTR3697.
The main objective of this study was to obtain chitosan functionalized viscose fabric with improved antibacterial properties and washing durability. In this regard carboxyl and aldehyde groups, as binding points for irreversible chitosan attachment into/onto viscose fabric, were introduced by two different pretreatments: 2,2,6,6-tetramethylpiperidine-1-oxy radical (TEMPO) oxidation and coating with TEMPO oxidized cellulose nanofibrils (TOCN). The Fourier transform infrared spectroscopy, elemental analysis, zeta potential measurements, scanning electron microscopy, breaking strength and antibacterial testing were used to evaluate the influence of these pretreatments on chitosan binding, but also on chemical, electrokinetic, morphological, mechanical and antibacterial properties of pretreated and chitosan functionalized viscose fabrics. Washing durability of chitosan functionalized viscose was monitored through changes in the chitosan content, electrokinetic and antibacterial properties after multiple washing. TOCN coating improves mechanical properties of fabric, while TEMPO oxidation deteriorates them. The results show that both pretreatments improve chitosan adsorption and thus antibacterial properties, which are highly durable to washing. After five washings, the chitosan functionalized pretreated viscose fabrics preserve their antibacterial activity against Staphylococcus aureus, while antibacterial activity against Escherichia coli was lost. TOCN coated and chitosan functionalized viscose fabric is a high value-added product with simultaneously improved antibacterial and mechanical properties, which may find application as medical textiles.
Aims/hypothesis Heterogeneity in individuals with type 1 diabetes has become more generally appreciated, but has not yet been extensively and systematically characterised. Here, we aimed to characterise type 1 diabetes heterogeneity by creating immunological, genetic and clinical profiles for individuals with juvenile-onset type 1 diabetes in a cross-sectional study. Methods Participants were HLA-genotyped to determine HLA-DR-DQ risk, and SNP-genotyped to generate a non-HLA genetic risk score (GRS) based on 93 type 1 diabetes-associated SNP variants outside the MHC region. Islet autoimmunity was assessed as T cell proliferation upon stimulation with the beta cell antigens GAD65, islet antigen-2 (IA-2), preproinsulin (PPI) and defective ribosomal product of the insulin gene (INS-DRIP). Clinical parameters were collected retrospectively. Results Of 80 individuals, 67 had proliferation responses to one or more islet antigens, with vast differences in the extent of proliferation. Based on the multitude and amplitude of the proliferation responses, individuals were clustered into non-, intermediate and high responders. High responders could not be characterised entirely by enrichment for the highest risk HLA-DR3-DQ2/DR4-DQ8 genotype. However, high responders did have a significantly higher non-HLA GRS. Clinically, high T cell responses to beta cell antigens did not reflect in worsened glycaemic control, increased complications, development of associated autoimmunity or younger age at disease onset. The number of beta cell antigens that an individual responded to increased with disease duration, pointing to chronic islet autoimmunity and epitope spreading. Conclusions/interpretation Collectively, these data provide new insights into type 1 diabetes disease heterogeneity and highlight the importance of stratifying patients on the basis of their genetic and autoimmune signatures for immunotherapy and personalised disease management.
BackgroundLeadless pacing is generally performed from a femoral approach. However, the femoral route is not always available. Until now, data regarding implantation using a jugular approach other than a single‐case report were lacking.MethodsThe case records of all patients who underwent internal jugular venous (IJV) leadless pacemaker implantation (Micra, Medtronic, Dublin, Ireland) at our center were analyzed retrospectively.ResultsNineteen patients underwent IJV leadless pacemaker implantation, nine females, mean age of 77.5 ±9.6 years; permanent atrial fibrillation in all patients with normal left ventricular ejection fraction. Implant indication was atrioventricular conduction disturbance in 10, pre‐AV node ablation in seven, and replacement of a conventional VVI pacemaker in two (infection in one and lead malfunction in the other). The device was positioned at the superior septum in seven patients, apicoseptal in seven patients, and midseptal in five patients. In 12 patients, a sufficient device position was obtained at the first attempt, in three at the second, in one at the third, in one at the fourth, and in two at the sixth attempt.The mean pacing threshold was 0.56 ± 0.39V at 0.24‐ms pulse width, sensed amplitude was 9.1 ± 3.2 mV, mean fluoroscopy duration was 3.1 ± 1.6 min. There were no vascular or other complications. At follow‐up, electrical parameters remained stable in 18 of 19 patients.ConclusionAlthough experience is minimal, we suggest that the IJV approach is safe and may be considered in patients where the femoral approach is contraindicated.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.