The gut microbiome is composed of a diverse population of bacteria that have beneficial and adverse effects on human health. The microbiome has recently gained attention and is increasingly noted to play a significant role in health and a number of disease states. Increasing urea concentration during chronic kidney disease (CKD) leads to alterations in the intestinal flora that can increase production of gut-derived toxins and alter the intestinal epithelial barrier. These changes can lead to an acceleration of the process of kidney injury. A number of strategies have been proposed to interrupt this pathway of injury in CKD. The purpose of this review is to summarize the role of the gut microbiome in CKD, tools used to study this microbial population, and attempts to alter its composition for therapeutic purposes.

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Soft tissue fixation of implant and bioelectrodes relies on mechanical means (e.g. sutures, staples, screws), with associated complications of tissue perforation, scarring, and interfacial stress concentrations. Adhesive bioelectrodes address these shortcomings with voltage cured carbene-based bioadhesives, locally energized through graphene interdigitated electrodes.Electro-rheometry and adhesion structure activity relationships were explored with respect to voltage and electrolyte on bioelectrodes synthesized from graphene 3D-printed onto resorbable polyester substrates. Adhesive leachates effects on in vitro metabolism and human derived platelet rich plasma response serves to qualitatively assess biological response. The voltage activated bioadhesives are found to have gelation times of 60 sec or less with maximum shear storage modulus (G') of 3 kPa. Shear modulus mimics reported values for human soft tissues (0.1-10 kPa). The maximum adhesion strength achieved for the ~50 mg bioelectrode films is 170 g cm -2 (17 kPa), which exceeds the force required for tethering of electrodes on dynamic soft tissues. The method provides the groundwork for implantable bio/electrodes that may be permanently incorporated into soft tissues, vis-à-vis graphene backscattering wireless electronics since all components are bioresorbable.

Comprehensive patient education improves the choice and prevalence of HoD therapies. We further find that 3 sessions of CPE may provide needed resources for the large majority of subjects for adequate decision-making.

Objective To assess the association of industry funding with the characteristics, outcome, and reported quality of randomized controlled trials (RCTs) of drug therapy for rheumatoid arthritis (RA). Methods MEDLINE and Cochrane Central Register of Controlled Trials databases were searched to identify original RA drug therapy RCTs published in 2002–3 & 2006–7. Two reviewers independently assessed each RCT for the funding source, characteristics, outcome [positive (statistically significant result favoring experimental drug for the primary outcome) or not positive], and reporting of methodological measures whose inadequate performance may bias treatment effect assessment. RCTs registered at ClinicalTrials.gov and completed in the study years were assessed for publication bias. Results 103 eligible RCTs were identified with following funding sources: 58 (56.3%) industry; 19 (18.4%) non-profit; 6 (5.8%) mixed; and 20 (19.4%) unspecified. Industry funded RCTs had significantly more study centers and subjects; while non-profit funded RCTs had longer duration, and were more likely to study different treatment strategies. Outcome could be assessed for 86 (83.5%) RCTs. Funding source was not associated with higher likelihood of positive outcomes favoring the sponsored experimental drug [industry (75.5%), non-profit (68.8%), mixed (40%), and unspecified (81.2%); p = 0.37]. Industry funded RCTs had trend towards higher likelihood of non-publication (38.6% versus 16.7%, p = 0.093). Industry-funded RCTs reported more frequent performance of double-blinding, adequate participant flow description, and intention-to-treat analysis. Conclusion Industry funding was not associated with higher likelihood of positive outcomes of published drug therapy RCTs for RA, and reported better on some key RCT quality measures.

Voltage-activated adhesion is a relatively new discovery that relies on direct currents for initiation of crosslinking. Previous investigations have found that direct currents are linearly correlated to the migration rates of electrocuring, but this is limited by high voltages exceeding 100 V with instances of incomplete curing of voltage-activated adhesives on semiconducting substrates. Practical applications of electrocuring would benefit from lower voltages to mitigate high voltage risks, especially with regard to potential medical applications. Alternative electrocuring strategies based on alternating current (AC), electrolyte ionic radius, and temperature are evaluated herein. Square waveform AC electric fields are hypothesized to initiate a two-sided curing progression of voltage-activated adhesive (PAMAM-g-diazirine aka Voltaglue), where initiation occurs at the cathode terminal. Structure-activity relationships of AC frequency at currents of 1-3 mA are evaluated against direct currents, migration rate, storage modulus, and lap shear adhesion on ex-vivo tissue mimics. Numerous improvements in electrocuring are observed with AC stimulation versus DC, including a 35 % decrease in maximum voltage, 180 % improvement in kinetic rates, and 100 % increase in lap shear adhesion at 2 mA. Li + ion electrolytes and curing at 4 o C shift curing kinetics by +104 % and -22 % with respect to the control ion (Na + ion at 24 o C), suggesting electrolyte migration is the rate limiting step. Li + ion electrolytes and curing at 50 o C improves storage modulus by 110% and 470 % respectively. Further evaluations of electrocured matrices with 19 F NMR, solid-state NMR and infrared spectroscopy provide insights into the probable crosslinking mechanisms.

The complex motion of the beating heart is accomplished by the spatial arrangement of contracting cardiomyocytes with varying orientation across the transmural layers, which is difficult to imitate in organic or synthetic models. High-fidelity testing of intracardiac devices requires anthropomorphic, dynamic cardiac models that represent this complex motion while maintaining the intricate anatomical structures inside the heart. In this work, we introduce a biorobotic hybrid heart that preserves organic intracardiac structures and mimics cardiac motion by replicating the cardiac myofiber architecture of the left ventricle. The heart model is composed of organic endocardial tissue from a preserved explanted heart with intact intracardiac structures and an active synthetic myocardium that drives the motion of the heart. Inspired by the helical ventricular myocardial band theory, we used diffusion tensor magnetic resonance imaging and tractography of an unraveled organic myocardial band to guide the design of individual soft robotic actuators in a synthetic myocardial band. The active soft tissue mimic was adhered to the organic endocardial tissue in a helical fashion using a custom-designed adhesive to form a flexible, conformable, and watertight organosynthetic interface. The resulting biorobotic hybrid heart simulates the contractile motion of the native heart, compared with in vivo and in silico heart models. In summary, we demonstrate a unique approach fabricating a biomimetic heart model with faithful representation of cardiac motion and endocardial tissue anatomy. These innovations represent important advances toward the unmet need for a high-fidelity in vitro cardiac simulator for preclinical testing of intracardiac devices.

Light chain deposition disease (LCDD) is characterized by monotypic immunoglobulin depositions which will eventually lead to loss of organ function if left untreated. While the kidney is almost always affected, the presence and degree of LCDD in other organs vary. Ten to thirty percent of LCDD patients have underlying Multiple Myeloma (MM), yet outcome and prognostic markers in this particular patient group are still lacking. Here, we analyzed 69 patients with MM and biopsy proven LCDD and report on renal and extra-renal involvement and its impact on prognosis as well as renal response depending on hematologic response. Coexisting light chain diseases such as AL amyloid and cast nephropathy were found in 30% of patients; those with LCDD and concurrent amyloid tended to have shorter survival. Cardiac involvement by LCDD was seen in one-third of our patients and was associated with shorter overall survival; such patients also had a significantly higher risk of treatment-related mortality (TRM) after stem cell transplant (SCT) compared to LCDD patients without cardiac involvement. This study highlights that MM patients with LCDD present with different clinical features compared to previously reported LCDD cohorts. Rapid initiation of treatment is necessary to prevent progressive renal disease and worse outcome. Coexisting light chain diseases and cardiac involvement are more common than previously reported and confer worse clinical outcome, emphasizing the need for careful patient careful patient evaluation and treatment selection.