The alternative complement pathway contributes to the development of IBMIR and the early loss of grafts in NHPs with porcine ITx. Complement inhibition during the peritransplant period may be beneficial for the survival of islet grafts.
Post-operative pancreatic fistula (POPF) following pancreatic resection is a life-threatening surgical complication. Cell sheets were prepared and harvested using temperature-responsive culture dishes and transplanted as patches to seal POPF. Two different mesenchymal stem cell (MSC) sheets were compared in terms of the preventative ability for pancreatic leakage in a rat model. Both rat adipose-derived stem cell (rADSC) and bone marrow-derived stem cell (rBMSC) sheets were transplanted. Those rADSC and rBMSC sheets are created without enzymes and thus maintained their cell-cell junctions and adhesion proteins with intact fibronectin on the basal side, as well as characteristics of MSCs. The rats with post-pancreatectomy rADSC- or rBMSC-sheet patches had significantly decreased abdominal fluid leakage compared with the control group, demonstrated by MR image analysis and measurement of the volume of abdominal fluid. Amylase level was significantly lower in the rats with rADSC-sheet and rBMSC-sheet patches compared with the control groups. The rADSC sheet patches had increased adhesive and immune-cytokine profiles (ICAM-1, L-selectin, TIMP-1), and the rBMSC sheets had reduced immune reactions compared to the control. This is first project looking at the feasibility of tissue engineering therapy using MSC-sheets as tissue patches preventing leakage of abdominal fluid caused by POPF.
Ruthenium (Ru) thin films were grown on thermally-grown SiO2 substrate using atomic layer deposition (ALD) by a sequential supply of a zero-valent metallorganic precursor, (ethylbenzyl) (1-ethyl-1,4-cyclohexadienyl)Ru(0) (EBECHRu, C16H22Ru), and molecular oxygen (O2) between 140 and 350°C while the typical temperature was 225°C. A self-limiting film growth was confirmed at the deposition temperature of 225°C and the growth rate was ∼0.042 nm/cycle on the SiO2 substrate with a negligible number of incubation cycles (approximately 3 cycles). Plan-view transmission electron microscopy analysis showed that nucleation was started after only 3 ALD cycles and the maximum nuclei density of 1.67 × 1012/cm2 was obtained after 7 ALD cycles. A continuous Ru film with a thickness of ∼2.3 nm was formed after 60 ALD cycles. The film resistivity was decreased with increasing deposition temperature, which was closely related to its crystallinity and microstructure, and the minimum resistivity of ∼14 μΩ-cm was obtained at the deposition temperature of 350°C. The step coverage of the film deposited between 225 and 270°C was approximately 100% over the contact holes (bottom diameter: 0.065 μm) with a high aspect ratio (32:1). Finally, the ALD-Ru film was successfully evaluated in terms of its performance as a seed layer for Cu electroplating and as a bottom electrode for a metal-insulator-metal capacitor using an ALD-TiO2 single layer or an ALD HfO2/La2O3/HfO2 multilayer as a dielectric.
Screening of matrix metalloproteinase (MMP)-14 substrates in human plasma using a proteomics approach previously identified apolipoprotein A-IV (apoA-IV) as a novel substrate for MMP-14. Here, we show that among the tested MMPs, purified apoA-IV is most susceptible to cleavage by MMP-7, and that apoA-IV in plasma can be cleaved more efficiently by MMP-7 than MMP-14. Purified recombinant apoA-IV (44-kDa) was cleaved by MMP-7 into several fragments of 41, 32, 29, 27, 24, 22 and 19 kDa. N-terminal sequencing of the fragments identified two internal cleavage sites for MMP-7 in the apoA-IV sequence, between Glu(185) and Leu(186), and between Glu(262) and Leu(263). The cleavage of lipid-bound apoA-IV by MMP-7 was less efficient than that of lipid-free apoA-IV. Further, MMP-7-mediated cleavage of apoA-IV resulted in a rapid loss of its intrinsic anti-oxidant activity. Based on the fact that apoA-IV plays important roles in lipid metabolism and possesses anti-oxidant activity, we suggest that cleavage of lipid-free apoA-IV by MMP-7 has pathological implications in the development of hyperlipidemia and atherosclerosis.
BackgroundAlthough transcranial direct current stimulation (tDCS) is known to be a promising therapeutic modality for unipolar depression, the efficacy and safety of tDCS for bipolar depressive episodes (BD) are still unknown and clinical trials of home-based tDCS treatment are scarce. As a result, we set out to investigate the efficacy and safety of home-based tDCS for the treatment BD.MethodsParticipants (n = 64), diagnosed as bipolar disorder as per the diagnostic and statistical manual of mental disorders (DSM-5), were randomly assigned to receive tDCS. Hamilton Depression Rating Scale (HDRS-17) scores were measured at the baseline, week 2, 4, and 6, and home-based tDCS (for 30 min with 2 mA) was self-administered daily.ResultsOf the 64 patients (15.6% bipolar disorder I, 84.4% bipolar disorder II), 41 patients completed the entire assessment. In the intention-to-treat analysis, time-group interaction for the HDRS-17 [F(3, 146.36) = 2.060; p = 0.108] and adverse effect differences between two groups were not statistically significant, except the pain score, which was higher in the active group than the sham group (week 0–2: p < 0.01, week 2–4: p < 0.05, and week 4–6: p < 0.01).ConclusionEven though we found no evidence for the efficacy of home-based tDCS for patients with BD, this tool was found to be a safe and tolerable treatment modality for BD.Clinical trial registration[https://clinicaltrials.gov/show/NCT03974815], identifier [NCT03974815].
Background/Aimsβ2-microglobulin (β2-MG) is freely filtered at the glomerulus and subsequently reabsorbed and catabolized by proximal renal tubular cells. Urinary β2-MG is an early and sensitive biomarker of acute kidney injury; however, its utility as a biomarker of immunoglobulin A nephropathy (IgAN) is unclear.MethodsWe included urinary β2-MG levels in the routine laboratory examination of all inpatients with biopsy-proven IgAN at our hospital from 2006 to 2010. We retrospectively analyzed the correlation between β2-MG levels and clinical parameters as a prognostic biomarker of IgAN.ResultsA total of 51 patients (30 males, 21 females; mean age, 33.01 ± 12.73 years) with IgAN were included in this study. Initial demographic, clinical, and laboratory data for all patients are listed. The mean initial estimated glomerular filtration rate and 24-hour urine protein levels were 94.69 ± 34.78 mL/min/1.73 m2 and 1.28 ± 1.75 g/day, respectively. The mean level of urinary β2-MG was 1.92 ± 7.38 µg/mg creatinine. There was a significant correlation between initial serum creatinine (iSCr), urine protein creatinine ratio (UPCR), and the level of β2-MG (r = 0.744, r = 0.667, p < 0.01). There was also a significant correlation between renal function tests and the level of urinary β2-MG (p < 0.01). Cox regression analysis showed that albumin, β2-MG, iSCr, and UPCR were significant predictors of disease progression in IgAN.ConclusionsUrinary β2-MG levels showed a significant correlation with renal function and proteinuria in IgAN. Thus, we propose that urinary β2-MG may be an additional prognostic factor in patients with IgAN.
Objective: This review will focus on how AI-and, specifically, deep learning-can be applied to complement aspects of the current healthcare system. We describe how AI-based tools can augment existing clinical workflows by discussing the applications of AI to worklist prioritization and patient triage, the performance-boosting effects of AI as a second reader, and the use of AI to facilitate complex quantifications.We also introduce prominent examples of recent AI applications, such as tuberculosis screening in resourceconstrained environments, the detection of lung cancer with screening CT, and the diagnosis of COVID-19.We also provide examples of prognostic predictions and new discoveries beyond existing clinical practices. Background: Artificial intelligence (AI) has shown promising performance for thoracic diseases, particularly in the field of thoracic radiology. However, it has not yet been established how AI-based image analysis systems can help physicians in clinical practice. Methods: This review included peer-reviewed research articles on AI in the thorax published in English between 2015 and 2021. Conclusions: With advances in technology and appropriate preparation of physicians, AI could address various clinical problems that have not been solved due to a lack of clinical resources or technological limitations.
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