Pig islets are an alternative source for islet transplantation to treat type 1 diabetes (T1D), but reproducible curative potential in the pig‐to‐nonhuman primate (NHP) model has not been ...demonstrated. Here, we report that pig islet grafts survived and maintained normoglycemia for >6 months in four of five consecutive immunosuppressed NHPs. Pig islets were isolated from designated pathogen‐free (DPF) miniature pigs and infused intraportally into streptozotocin‐induced diabetic rhesus monkeys under pretreatment with cobra venom factor (CVF), anti‐thymocyte globulin (ATG) induction and maintenance with anti‐CD154 monoclonal antibody and low‐dose sirolimus. Ex vivo expanded autologous regulatory T cells were adoptively transferred in three recipients. Blood glucose levels were promptly normalized in all five monkeys and normoglycemia (90–110 mg/dL) was maintained for >6 months in four cases, the longest currently up to 603 days. Intravenous glucose tolerance tests during the follow‐up period showed excellent glucose disposal capacity and porcine C‐peptide responses. Adoptive transfer of autologous regulatory T cells was likely to be associated with more stable and durable normoglycemia. Importantly, the recipients showed no serious adverse effects. Taken together, our results confirm the clinical feasibility of pig islet transplantation to treat T1D patients without the need for excessive immunosuppressive therapy.
The authors report control of diabetes for longer than six months in four consecutive nonhuman primates by the transplantation of adult pig islets using a modest immunosuppressive regimen with an acceptable adverse effect profile.
Summary
To compare the diagnosis andtreatment rates of osteoporosis and diabetes in Korea, a nationwide database was used. The results showed that although osteoporosis management is improving, it is ...still lower compared with that of diabetes; thus, further efforts are needed in this regard.
Introduction
This study aimed to re-evaluate the diagnosis and treatment of osteoporosis from the KNHANES 2016–2017 and compare the temporal change of the rate with those of diabetes as another prevalent chronic disease in South Korea.
Methods
The prevalence of osteoporosis in 2016 was estimated using the previous data classified by age groups (50–59,60–69, and ≥70years) and the 2016 Korean census data. The physician diagnosis and treatment rates of osteoporosis in adults aged ≥50years were estimated using the 2016–2017 KNHANES data. The physician diagnosis and treatment rates of diabetes were evaluated using the KNHANES 2008–2009 and 2016–2017 data.
Results
The estimated physician diagnosisrate of osteoporosis increased from 29.9% in females and 5.8% in males in 2008–2009 to 62.8% in females and 22.8% in males in 2016–2017. The treatment rate for the estimated total number of patients with osteoporosis increased from 14.4% in females and 3.8% in males in 2008–2009 to 32.2% in females and 9.0% in males in 2016–2017. An increasing trend in the estimated treatment rateof physician-diagnosed osteoporosis patients was not observed (48.3% 2008–2009 vs 51.5% 2016–2017 in females; 42.6% 2008–2009 vs 42.2% 2016–2017 in males). The physician diagnosis and treatment rates of diabetes were considerably better and more stable than those of osteoporosis.
Conclusion
Osteoporosis management in South Korea is improving but is insufficient compared with diabetes management. More extensive efforts are needed to improve the diagnosis and treatment rates of osteoporosis.
Rapid phagocytic clearance of apoptotic cells is crucial for the prevention of both inflammation and autoimmune responses. Phosphatidylserine (PS) at the external surface of the plasma membrane has ...been proposed to function as a general 'eat me' signal for apoptotic cells. Although several soluble bridging molecules have been suggested for the recognition of PS, the PS-specific membrane receptor that binds directly to the exposed PS and provides a tickling signal has yet to be definitively identified. In this study, we provide evidence that stabilin-2 is a novel PS receptor, which performs a key function in the rapid clearance of cell corpses. It recognizes PS on aged red blood cells and apoptotic cells, and mediates their engulfment. The downregulation of stabilin-2 expression in macrophages significantly inhibits phagocytosis, and anti-stabilin-2 monoclonal antibody provokes the release of the anti-inflammatory cytokine, transforming growth factor-beta. Furthermore, the results of time-lapse video analyses indicate that stabilin-2 performs a crucial function in the rapid clearance of aged and apoptotic cells. These data indicate that stabilin-2 is the first of the membrane PS receptors to provide tethering and tickling signals, and may also be involved in the resolution of inflammation and the prevention of autoimmunity.
Next-generation wearable electronics require enhanced mechanical robustness and device complexity. Besides previously reported softness and stretchability, desired merits for practical use include ...elasticity, solvent resistance, facile patternability and high charge carrier mobility. Here, we show a molecular design concept that simultaneously achieves all these targeted properties in both polymeric semiconductors and dielectrics, without compromising electrical performance. This is enabled by covalently-embedded in-situ rubber matrix (iRUM) formation through good mixing of iRUM precursors with polymer electronic materials, and finely-controlled composite film morphology built on azide crosslinking chemistry which leverages different reactivities with C-H and C=C bonds. The high covalent crosslinking density results in both superior elasticity and solvent resistance. When applied in stretchable transistors, the iRUM-semiconductor film retained its mobility after stretching to 100% strain, and exhibited record-high mobility retention of 1 cm
V
s
after 1000 stretching-releasing cycles at 50% strain. The cycling life was stably extended to 5000 cycles, five times longer than all reported semiconductors. Furthermore, we fabricated elastic transistors via consecutively photo-patterning of the dielectric and semiconducting layers, demonstrating the potential of solution-processed multilayer device manufacturing. The iRUM represents a molecule-level design approach towards robust skin-inspired electronics.
Abstract The purpose of this study was to evaluate the volumetric change of the upper airway space in 36 Class III patients who had undergone bimaxillary surgery or isolated mandibular setback, and, ...further, to analyse the relation between post-surgical stability and airway change using cone-beam computed tomography (CBCT). A three-dimensional (3D) CBCT examination was performed at three stages: T0 (before surgery), T1 (an average of 4.6 months after surgery), and T2 (an average of 1.4 years after surgery). The results showed that the volumes of the oropharyngeal and hypopharyngeal airways decreased significantly 4.6 months post-surgery in the mandibular setback group ( p < 0.05), and these diminished airways had not recovered 1.4 years post-surgery. In the bimaxillary surgery group, the volume of the oropharyngeal airway also decreased. A Spearman correlation analysis showed that the anteroposterior length of the hypopharyngeal area had a correlation with post-surgical stability in the isolated mandibular surgery group, and that the cross-sectional area of the nasopharynx was correlated with maxillary relapse only in the bimaxillary surgery group ( p < 0.05).
Objectives were to provide an overview and understand the strength of evidence and extent of potential biases and validity of claimed associations between body mass index (BMI) and risk of developing ...cancer.
We carried out an umbrella review and comprehensively re-analyzed the data of dose–response meta-analyses on associations between BMI and risk of 20 specific cancers (bladder, brain, breast, colonic, rectal, endometrial, gallbladder, gastric, leukemia, liver, lung, melanoma, multiple myeloma, non-Hodgkins lymphoma, esophagus, ovarian, pancreatic, prostate, renal, thyroid) by adding big data or missed individual studies. Convincing evidence for an association was defined as a strong statistical significance in fixed-effects and random-effects meta-analyses at P<0.001, 95% prediction interval (PI) excluded null, there was no large between-study heterogeneity and no small study effects. Suggestive evidence was defined as meeting the significance threshold for the random summary effects of P<0.05, but 95% PI included the null. Weak evidence was defined as meeting the significance threshold for the random summary effects at a P<0.05, but 95% PI included the null and there was large between-study heterogeneity or there were small study effects.
Convincing evidence for an association with BMI was detectable for six cancers (leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma). Suggestive evidence was detectable for malignant melanoma, non-Hodgkins lymphoma, and esophageal adenocarcinoma. Weak evidence was detectable for brain and central nervous system tumors, breast, colon, gall bladder, lung, liver, ovarian, and thyroid cancer. No evidence was detectable for bladder, gastric, and prostate cancer.
The association of increased BMI and cancer is heterogeneous across cancer types. Leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma are convincingly associated with an increased BMI by dose–response meta-analyses.
Metabolic syndromes are prevalent worldwide and result in various complications including obesity, cardiovascular disease and type II diabetes. Betulinic acid (BA) is a naturally occurring ...triterpenoid that has anti-inflammatory properties. We hypothesized that treatment with BA may result in decreased body weight gain, adiposity and hepatic steatosis in a diet-induced mouse model of obesity.
Mice fed a high-fat diet and treated with BA showed less weight gain and tissue adiposity without any change in calorie intake. Gene expression profiling of mouse tissues and cell lines revealed that BA treatment increased expression of lipid oxidative genes and decreased that of lipogenesis-related genes. This modulation was mediated by increased AMP-activated protein kinase (AMPK) phosphorylation, which facilitates energy expenditure, lipid oxidation and thermogenic capacity and exerts protective effects against obesity and nonalcoholic fatty liver disease. Overall, BA markedly inhibited the development of obesity and nonalcoholic fatty liver disease in mice fed a high-fat diet, and AMPK activation in various tissues and enhanced thermogenesis are two possible mechanisms underlying the antiobesity and antisteatogenic effects of BA.
The current findings suggest that treatment with BA is a potential dietary strategy for preventing obesity and nonalcoholic fatty liver disease.
•Betulinic acid (BA) decreased body weight gain, adiposity and hepatic steatosis in a diet-induced obese mouse model.•BA treatment increased expression of lipid oxidative genes and decreased mRNA expression related to lipogenesis.•BA treatment enhanced activation of AMPK, which facilitates energy expenditure, lipid oxidation and thermogenesis.•BA intake may be a potential dietary strategy for preventing obesity and nonalcoholic fatty liver disease.
Background and purpose
Hemorrhagic transformation (HT) is one of the most problematic complications to arise from intravenous thrombolysis (IVT). This study was conducted to assess whether micro‐ and ...macroalbuminuria could be associated with HT after IVT in patients with acute ischaemic stroke, and to investigate whether the value of urinary albumin‐to‐creatinine ratios would correlate with the degree of HT.
Methods
This was a retrospective study of stroke patients who had undergone IVT within 3 h of symptom onset. Albuminuria assessment was based on random morning spot urine collection with patients in a fasting state, the first morning after IVT. Multiple logistic regression analysis was used to evaluate whether the presence of micro‐ and macroalbuminuria might be independent predictors of HT.
Results
One‐hundred and fifty‐four patients were included in the study. Fifty‐one patients had HT. The presence of micro‐ or macroalbuminuria was associated with HT after adjustment for variables with clinical significance (adjusting for age, atrial fibrillation, platelet counts, baseline National Institutes of Health Stroke Scale score, hypertension and diabetes mellitus; odds ratio, 2.542; 95% confidence interval, 1.106–5.841; P = 0.028). There were significant relationships between the presence of micro‐ and macroalbuminuria and types of HT.
Conclusion
In conclusion, the results of this study suggest that the presence of micro‐ and macroalbuminuria after IVT could be a predictor of severe HT in patients with acute ischaemic stroke.
Skin-like sensory devices should be stretchable and self-healable to meet the demands for future electronic skin applications. Despite recent notable advances in skin-inspired electronic materials, ...it remains challenging to confer these desired functionalities to an active semiconductor. Here, we report a strain-sensitive, stretchable, and autonomously self-healable semiconducting film achieved through blending of a polymer semiconductor and a self-healable elastomer, both of which are dynamically cross-linked by metal coordination. We observed that by controlling the percolation threshold of the polymer semiconductor, the blend film became strain sensitive, with a gauge factor of 5.75 × 10
at 100% strain in a stretchable transistor. The blend film is also highly stretchable (fracture strain, >1300%) and autonomously self-healable at room temperature. We proceed to demonstrate a fully integrated 5 × 5 stretchable active-matrix transistor sensor array capable of detecting strain distribution through surface deformation.
Abstract Background Long-term prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC) with macroscopic bile duct tumor thrombus (BDTT) has not been well assessed. This study ...intended to analyze the post-transplantation outcomes in patients who had HCC with macroscopic BDTT. Methods A retrospective study was performed with 14 patients who underwent LT for HCC with BDTT (0.7%) after selection from an institutional database of 2052 adult LT cases. Results Types of LT were living donor LT in 13 and deceased donor LT in 1. The extents of BDTT were Ueda type 1 in 4, type 2 in 3, and type 3 in 7. Milan criteria were met in 8 (57.1%). Concurrent bile duct resection was performed in 7 (50%). Mean model for end-stage liver disease score was 18.7 ± 4.9. Mean graft-recipient weight ratio was 1.2 ± 0.3. There was one case of perioperative mortality and one case of HCC-unrelated late mortality. Cumulative HCC recurrence rates were 15.4% at 1 year, 46.2% at 3 years, and 46.2% at 5 years. Overall patient survival rates were 92.9% at 1 year, 57.1% at 3 years, and 50% at 5 years. Univariate risk factor analyses revealed that only macrovascular invasion was a significant risk factor for HCC recurrence ( P = .019). Conclusions The results of this study revealed that LT for HCC with macroscopic BDTT has a high risk of post-transplantation HCC recurrence; therefore, further large-volume studies are necessary to elucidate the risk factors.
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