Evaluation of Mesh Size in Model Polymer Networks Consisting of Tetra-Arm and Linear Poly(ethylene glycol)s

The structure and mechanical properties of model polymer networks consisting of alternating tetra-functional poly(ethylene glycol)s (PEGs) and bis-functional linear PEGs were investigated by dynamic light scattering and rheological measurements. The sizes of the correlation blob ( ξ c ) and the elastic blob ( ξ e l ) were obtained from these measurements and compared to the theoretical mesh size, the geometric blob ( ξ g ), calculated by using the tree-like approximation. By fixing the concentration of tetra-PEGs and tuning the molecular weight of linear-PEGs, we systematically compared these blob sizes in two cases: complete network (Case A) and incomplete network (Case B). The correlation blob, ξ c , obtained by dynamic light scattering (DLS) was found to obey the well-known concentration dependence for polymer solutions in semidilute regime ( ξ c ~ ϕ − 3 / 4 ) irrespective of the Cases. On the other hand, the G ′ was strongly dependent on the Cases: For Case A, G ′ was weakly dependent on the molecular weight of linear-PEGs ( G ′ ~ M c 0.69 ) while G ′ for Case B was a strong increasing function of M c   ( G ′ ~ M c 1.2 ). However, both of them are different from the geometric blob (theoretical mesh) of the gel networks. In addition, interesting relationships between G ′ and ξ c , G ′ ~ ξ c , G ′ ~ ξ C − 2 , were obtained for Cases A and B, respectively

Neutralization and Salt Effect on the Structure and Mechanical Properties of Polyacrylic Acid Gels under Equivolume Conditions

The effects of neutralization and salt on the structure and mechanical properties of polyacrylic acid (PAA) gels under equivolume conditions were investigated by small-angle X-ray scattering (SAXS) measurements and tensile tests. We attained the equivolume condition by immersing a piece of PAA gel sample in an ion reservoir containing linear PAA, NaOH, and NaCl at prescribed concentrations (post-ion-tuning). The volume fraction of the linear polymer was set to be the same as that of the gel so as to satisfy the iso-osmotic pressure at the reference state. Various types of reservoirs were prepared by adding NaOH and/or NaCl with different concentrations to the reference reservoir, followed by immersing a PAA gel piece. In the SAXS measurements, a scattering peak appeared, and the scattering intensity at q = 0 decreased by neutralization, while the addition of salt increased the scattering intensity. On the other hand, Young’s modulus measured with the tensile test decreased with neutralization; however, it scarcely changed with the addition of salt. The newly developed equivolume post-ion-tuning technique may serve as a new standard scheme to study polyelectrolyte gels

Case of fulminant type 1 diabetes induced by the anti-programmed death-ligand 1 antibody, avelumab

With the expansive use of immune checkpoint inhibitors, the frequency of immune-related adverse events, including autoimmune type 1 diabetes, has been exponentially increased. The anti-programmed death-ligand 1 antibody, avelumab, has recently been approved for metastatic Merkel cell carcinoma therapy. Here, we report a patient that developed fulminant type 1 diabetes during avelumab treatment. An 81-year-old woman with no history of diabetes received avelumab for metastatic Merkel cell carcinoma. Elevated plasma glucose level (483 mg/dL), hemoglobin A1c level (7.5%) and ketosis were observed after 10 courses of avelumab without any symptoms related to hyperglycemia. As the laboratory tests showed insulin depletion, we diagnosed her with fulminant type 1 diabetes induced by avelumab. This is the first reported case of avelumab-induced type 1 diabetes, illustrating the necessity for close monitoring of glycemic control during avelumab therapy, as well as other immune checkpoint inhibitors

The risk factors for hepatic steatosis in patients with primary aldosteronism

Patients with primary aldosteronism (PA) are complicated by metabolic syndrome more frequently than those without PA. Hyperaldosteronism has been reported to be associated with a higher prevalence of non-alcoholic fatty liver disease (NAFLD). We aimed to clarify the risk factors for hepatic steatosis in the two subtypes of PA, comparing the status of hepatic steatosis in each of these subtypes. This was a retrospective observational study. We enrolled patients with an aldosterone producing adenoma (APA) (n = 33) or idiopathic hyperaldosteronism (IHA) (n = 56). Hepatic fat content was evaluated using the ratio of liver to spleen (L/S) X-ray attenuation on unenhanced computed tomography. L/S ratio <1.0 was utilized for assessing as hepatic steatosis. Age, sex distribution, visceral fat percentage (VF%), and visceral fat area (VFA) did not differ between patients with the two PA subtypes. The percentages of patients with L/S ratio <1.0 was not different between the two subtypes (APA: 21.2 % (7/33) vs. IHA: 19.6 % (11/56), p = 1.00). In both subtypes, the L/S ratio negatively correlated with VF% (APA: r = -0.66, p < 0.001; IHA: r = -0.66, p < 0.001) and with VFA (APA: r = -0.44, p < 0.01; IHA: r = -0.37, p < 0.01). The status of hepatic steatosis, evaluated using L/S ratio, did not differ between patients with APA or IHA. Hepatic steatosis was affected by the amount of visceral fat

Sodium-glucose cotransporter 2 inhibitors reduce day-to-day glucose variability in patients with type 1 diabetes

Aims/Introduction Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are used worldwide because of their multiple benefits for patients with type 2 diabetes. The purpose of this study was to determine the efficacy and safety of SGLT2i in patients with type 1 diabetes. Materials and Methods Patients with type 1 diabetes who had been treated with SGLT2i for >12 weeks were included in this retrospective observation study. We recorded the changes in body mass, insulin dose, blood and urine test data, and adverse events. The changes in day-to-day glucose variability, as the primary end-point, was evaluated using the interquartile range (P25/P75) of the ambulatory glucose data obtained using continuous glucose monitoring. Results A total of 51 patients (37 women; mean age 52.7 years) were included. Glycated hemoglobin and body mass significantly decreased by 0.4% and 1.6 kg, respectively. The total required insulin dose decreased by 9.4% (42.7 +/- 26.6-38.7 +/- 24.3 units/day). Continuous glucose monitoring data were obtained from 30 patients. P25/P75 decreased by 17.6 +/- 20.7% during SGLT2i treatment (P < 0.001). The percentage of time per day within the target glucose range of 70-180 mg/dL significantly increased (from 42.2 to 55.5%,P < 0.001), without an increase in the percentage of time spent in the hypoglycemic range (<70 mg/dL). Urinary ketone bodies were detected in four patients (7.8%), but none developed ketoacidosis. Conclusions SGLT2i improved day-to-day glucose variability and time in the target glucose range, without increasing frequency of hypoglycemia, in patients with type 1 diabetes, and reduced glycated hemoglobin, body mass and the required insulin dose