Removal of α1-Microglobulin Using Post-Dilution Online Hemodiafiltration with Polymethylmethacrylate Membrane: An Open-Label, Single-Arm Study.

INTRODUCTION: The removal of low- and medium-molecular-weight proteins has been improved with online hemodiafiltration (OL-HDF) and hemodialysis using high-flux membranes; however, the outcomes of patients with end-stage kidney disease (ESKD) undergoing dialysis treatment are still worse than in the general population. α1-Microglobulin (α1-m), with a molecular weight of 33,000 Da, may contribute to dialysis-related disorders and mortality. However, the removal is insufficient even with current OL-HDF using the polysulfone (PS) membrane, which is common in Japan. Polymethylmethacrylate (PMMA) membranes can remove medium- to high-molecular-weight proteins by adsorption. This study aimed to assess the efficacy of removing medium- to high-molecular-weight proteins, such as α1-m and ß2-microglobulin (ß2-m), through post-dilution OL-HDF with PMMA (Post-PMMA). The assessment was conducted in comparison to pre-dilution OL-HDF with PS (Pre-PS), using an open-label, single-arm study. METHODS: Seven patients with ESKD on Pre-PS underwent Post-PMMA with replacement volume of 30 mL/min (low flow) and 50 mL/min (high flow). Clearance and removal rates of α1-m, ß2-m, small molecules, inflammatory cytokines, and albumin were measured at 60 and 240 min of treatment. RESULTS: Clearance rates of α1-m at 60 min were -2.8 ± 5.2 mL/min with Pre-PS, -0.4 ± 2.6 mL/min with Post-PMMA (low), and 0.6 ± 3.4 mL/min with Post-PMMA (high). The removal rate of α1-m was higher in Post-PMMA than that in Pre-HDF-PS (Post-PMMA [high] 17.7 ± 5.9%, Post-PMMA [low] 15.0 ± 5.6%, and Pre-PS 4.1 ± 5.5%). Adsorption clearance of ß2-m was increased with Post-PMMA. Albumin leakage in Post-PMMA was not higher than that in Pre-PS. CONCLUSION: The removal rate of α1-m with Post-PMMA was higher than that with Pre-PS. The PMMA membrane adsorbed ß2-m, suggesting the removal effect of medium- to high-molecular-weight proteins by the adsorption method. Since Post-PMMA effectively removes α1-m without excessive albumin leakage, it will be useful for patients with ESKD, especially those with a poor nutritional status.

Northward expansion of the bivoltine life cycle of the cricket over the last four decades.

Recent climate warming has affected some life-history traits of insects, including voltinism and body size. The magnitude of changes in these traits may differ latitudinally within a species because of the differing lengths of season available for growth. The present study aims to estimate the change in voltinism of the lawn ground cricket, Polionemobius mikado (Shiraki) (Orthoptera: Trigonidiidae), over the last four decades by comparing the body size between adults collected from a wide range of latitudes in Japan in recent years (2015-2017) and those collected four decades ago (1969-1976). The body size of adults collected in recent years showed a latitudinal saw-tooth cline, in the same way as body size did four decades ago, and the cline shifted northward over the last four decades: In 2015-2017, the body size decreased slightly with increasing latitude from 31°N to 36°N, and then increased to 40°N, and again decreased from 40°N to 44°N. Comparison of the body size between recent years and four decades ago revealed that the body size has decreased significantly at the middle latitudes (36-40°N), suggesting that the proportion of smaller bivoltine individuals there has increased over the last four decades. The sum of effective temperatures for postdiapause embryonic development at around 36°N in recent years was comparable to that at 31-35°N four decades ago, at which P. mikado populations were bivoltine. Taken together, these findings suggested that the latitudinal range suitable for the bivoltine life cycle of P. mikado has expanded northward over the last four decades because of climate warming. This is the first report that shows that a decrease in body size can be caused by climate warming via an increase in voltinism.

Adsorption of Protein-Bound Uremic Toxins Through Direct Hemoperfusion With Hexadecyl-Immobilized Cellulose Beads in Patients Undergoing Hemodialysis.

An accumulation of protein-bound uremic toxins (PBUTs) is one of major reasons for development of uremia-related complications. We examined the PBUT removal ability of a hexadecyl-immobilized cellulose bead (HICB)-containing column for patients undergoing hemodialysis. Adsorption of indoxyl sulfate (IS), a representative PBUT, to HICBs was examined in vitro. The HICB column was used in patients undergoing hemodialysis for direct hemoperfusion with a regular hemodialyzer. The serum IS, indole acetic acid (IAA), phenyl sulfate (PhS), and p-cresyl sulfate (PCS) levels were measured before and after passing the column. HICBs adsorbed protein-free (free) IS in a dose- and time-dependent manner in vitro (55.4 ± 1.4% adsorption of 1 millimolar, 251 µg/mL, IS for 1 h). In clinical studies, passing the HICB-containing column decreased the serum level of free IS, IAA, PhS, and PCS levels significantly (by 34.4 ± 30.0%, 34.8 ± 25.4%, 28.4 ± 18.0%, and 34.9 ± 22.1%, respectively), but not protein-bound toxins in maintenance hemodialysis patients. HICBs absorbed some amount of free PBUTs, but the clinical trial to use HICB column did not show effect to reduce serum PBUTs level in hemodialysis patients. Adsorption treatment by means of direct hemoperfusion with regular hemodialysis may become an attractive blood purification treatment to increase PBUT removal when more effective materials to adsorb PBUTs selectively will be developed.

Mass spectrometry-based proteomic analysis of proteins adsorbed by hexadecyl-immobilized cellulose bead column for the treatment of dialysis-related amyloidosis.

BACKGROUND: Dialysis-related amyloidosis (DRA) is a severe complication in end-stage kidney disease (ESKD) patients undergoing long-term dialysis treatment, characterized by the deposition of ß2-microglobulin-related amyloids (Aß2M amyloid). To inhibit DRA progression, hexadecyl-immobilized cellulose bead (HICB) columns are employed to adsorb circulating ß2-microglobulin (ß2M). However, it is possible that the HICB also adsorbs other molecules involved in amyloidogenesis. METHODS: We enrolled 14 ESKD patients using HICB columns for DRA treatment; proteins were extracted from HICBs following treatment and identified using liquid chromatography-linked mass spectrometry. We measured the removal rate of these proteins and examined the effect of those molecules on Aß2M amyloid fibril formation in vitro. RESULTS: We identified 200 proteins adsorbed by HICBs. Of these, 21 were also detected in the amyloid deposits in the carpal tunnels of patients with DRA. After passing through the HICB column and hemodialyzer, the serum levels of proteins such as ß2M, lysozyme, angiogenin, complement factor D and matrix Gla protein were reduced. These proteins acted in the Aß2M amyloid fibril formation. CONCLUSIONS: HICBs adsorbed diverse proteins in ESKD patients with DRA, including those detected in amyloid lesions. Direct hemoperfusion utilizing HICBs may play a role in acting Aß2M amyloidogenesis by reducing the amyloid-related proteins.

A contemporary meta-analysis of Dacron versus polytetrafluoroethylene grafts for femoropopliteal bypass grafting.

BACKGROUND: The present study provides a contemporary and comprehensive summation of midterm patency rates of polyester (Dacron) or polytetrafluoroethylene (PTFE) grafts in femoropopliteal bypass grafting based on a meta-analysis consisting only of randomized controlled trials. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify all randomized controlled trials of Dacron vs PTFE grafts in femoropopliteal bypass grafting. Seven trials were found. Survival data were combined to yield the pooled cumulative primary patency. We estimated the log hazard ratio (HR) for each 1-month interval and then combined the HRs in a stratified way across intervals to obtain an overall log HR for each trial. Study-specific estimates were combined using inverse variance-weighted averages of logarithmic HRs in fixed-effects and random-effects models. RESULTS: The pooled cumulative primary patency of Dacron and PTFE grafts was, respectively, 60.2% (95% confidence interval [CI], 56.4%-64.0%) and 53.8% (95% CI, 46.8%-60.9%) at 3 years, and 49.2% (95% CI, 45.6%-52.7%) and 38.4% (95% CI, 32.2%-44.6%) at 5 years. Pooled analysis of the seven trials demonstrated no difference in HR for graft occlusion with Dacron relative to PTFE grafts (random-effects HR, 0.87; 95% CI, 0.67-1.12; P = .27 for effect; P = .03 for heterogeneity). CONCLUSION: Either Dacron or PTFE grafts can be used in femoropopliteal bypass grafting with no significant differences in midterm graft patency at 5 years (49.2% vs 38.4%) when the autologous saphenous vein is unavailable.

Comparison of cervical spinal canal diameter between younger and elder generations of Japanese.

BACKGROUND: Cervical myelopathy is more common among Japanese than Westerners. The shorter anteroposterior diameter of the cervical spinal canals (AP diameter) is its probable cause. In recent years, builds of younger Japanese have become larger and been approaching those of Westerners. The purpose of this study was to investigate whether the cervical spinal canal had enlarged in the younger Japanese as well as any cross-sectional improvement in their builds. METHODS: The subjects included 300 men and 300 women who were healthy and without symptoms related to the cervical spine. They were divided into six age groups at 10-year intervals from the twenties to the seventies. Height, body weight, and arm span were measured as physical factors. Using lateral dynamic radiographs of the cervical spine, the AP diameter from C3 to C6 in the neutral position and Penning's jaw diameter in extension (jaw diameter) from C2/3 to C5/6 were measured. The number of trapezoid-shaped vertebral bodies with a thickened posterior margin were also counted as such thickening might be one of the causes of spinal canal narrowing. Statistical analysis was performed for the following associations in both sexes: (1) age and physical factors; (2) age and the AP diameter; (3) age and jaw diameter; and (4) the difference of the AP diameter of the canal within and outside the trapezoid-shaped deformity of the vertebral body. RESULTS: In both men and women, the younger generations statistically had a larger height, arm span, and AP diameter. Older generations showed a significantly narrower jaw diameter at all measured spinal levels in both sexes. Trapezoid-shaped vertebral bodies were found in 3.5% of the men and in 1.3% of the women in their fifties, sixties, and seventies, which statistically had no effect on the AP diameter being wider in the younger generations. CONCLUSIONS: Younger generations had larger builds and a wider canal of the cervical spine. A narrow spinal canal is a fundamental risk factor for cervical myelopathy. Therefore, cervical myelopathy might be expected to decrease in Japan in the near future when the present younger generations have aged.

Effect of additive metals, Sn, Ga, and In in Ag-Pd-Au-Cu alloys on initial bond strength of 4-META adhesive cement to these alloys.

The purpose of this study was to investigate the effects of three additives, Sn, Ga, and In, as well as the main constituents, Pd and Cu, of Ag-Pd-Au-Cu alloys on the initial bond strength of 4-META adhesive cement to these alloys. The Ag-Pd-Au-Cu alloys consisted of 20%, 30% or 40% Pd, and 10%, 15% or 20% Cu, 20% Au, and Ag as balance. Besides, additive metals (Sn, Ga, and In) of 2% and 4% were added to these compositions. The addition of three additives, in general, increased the initial bond strength of the cement in comparison to the mother compositions (0% additives), although the degrees of effectiveness of the three additives were different and varied with their contents. Among these additives, a remarkable increase in bond strength was observed with the addition of In. The increase in Cu content, in many cases, resulted in an increase in bond strength at high Pd contents (30% and 40%), but a decrease at low Pd content (20%) in some cases. The positive effects of the three additives and Cu could be due to the formation of a suitable oxide layer for strong bonding with 4-META.

Effects of heat treatments and Sn, Ga and In additives on mechanical properties of 35Ag-30Pd-20Au-15Cu alloy.

The mechanical properties of six 35Ag-30Pd-20Au-15Cu alloys containing different contents (2% and 4%) of Sn, Ga, or In and a 35Ag-30Pd-20Au-15Cu alloy without additives were evaluated. These alloys were subjected to four different heat treatments before a mechanical test. The distribution of the elements and their contents were analyzed. The mechanical properties of 35Ag-30Pd-20Au-15Cu alloy changed in wide-ranging ways with different heat treatments and with different additive contents. The effects of heat treatment on tensile strength and hardness significantly varied with different additives and their contents. These different changes could be attributed to the formation of different phases in these alloys. Based on the high strength and wide-ranging changes in the mechanical properties when subjected to softening and hardening heat treatments, the 2% Sn-added, 2% In-added, and 4% Ga-added alloys can be recommended for different dental restorations such as crown & bridges, inlays, and denture frameworks.

Correlation between accuracy of crowns fabricated using CAD/CAM and elastic deformation of CAD/CAM materials.

Full crowns were fabricated from three different materials (titanium, ceramic, and resin composite) at different rest diameters using a dental CAD/CAM system, and then their marginal discrepancy measured. The deflection of cylindrical specimens at 500 gf was measured using the same materials and diameters as for the accuracy measurement. Marginal discrepancy decreased as rest diameter increased, and at the same rest diameter the titanium crown had lower marginal discrepancy than ceramic and composite crowns. A significant correlation was found between marginal discrepancy of the crowns and deflection of the materials. This correlation was aptly expressed in the regression equation, MG = 4.54DF+53.9, where MG represented marginal discrepancy and DF represented deflection. This equation can be used as a good measure for new materials which have different modulus of elasticity.

Effects of Ga addition on the mechanical properties of 35Ag-30Pd-20Au-15Cu alloy.

Ten 35Ag-30Pd-20Au-15Cu alloys containing 0.00, 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00, 4.00, or 6.00% Ga were experimentally prepared to investigate the effect of Ga on their mechanical properties in addition to their use for denture frameworks, connectors and clasps. The effect of Ga addition on the mechanical properties was marked with a significant increase in the tensile strength, 0.2% off-set proof stress (proof stress) and Vickers hardness observed at low Ga contents (0.25-2.00%). On the other hand, the elongation significantly decreased with the addition of Ga at all contents used in this study. The tensile strength, proof stress and Vickers hardness of the 35Ag-30Pd-20Au-15Cu alloys containing 0.25-2.00% Ga were in the range of 809-957 MPa, 669-857 MPa and 260-301 MPa, respectively. These values are similar to those of Co-Cr alloys, suggesting that 0.25-2.00% Ga alloys can be used for denture frameworks, clasps and connectors.

Development of casting investment preventing blackening of noble metal alloys part 1. Application of developed investment for Ag-Pd-Cu-Au alloy.

The objective of this study is to develop a casting investment that prevents the blackening of the cast surface of noble metal alloys. The experimental investments were prepared using a gypsum-bonded investment in which the metallic powders such as boron (B), silicon (Si), aluminum (Al) and titanium (Ti) were added as oxidizing agents. An Ag-Pd-Cu-Au alloy was cast into the mold made of the prepared investment. The effect of the addition of each metal powder was evaluated from the color difference between the as-cast surface and the polished surface of the cast specimen. The color of the as-cast surface approached that of the polished surface with increasing B and Al content. A lower mean value in the color difference was obtained at 0.25-1.00 mass% B content. B and Al are useful as an additive in a gypsum-bonded investment to prevent the blackening of an Ag-Pd-Cu-Au alloy. The effects of Si and Ti powder addition could not be found.

Development of casting investment preventing blackening of noble metal alloys Part 2. Application of developed investment for type 4 gold alloy.

The objective of this study was to evaluate the efficacy of the developed investment for the prevention of blackening of a cast Type 4 gold and to analyze the oxides on its surface in relation to the blackening of the alloy. The experimental investments were prepared using a gypsum-bonded investment in which boron (B) or aluminum (Al) was added as a reducing agent. A Type 4 gold alloy was cast into the mold made of the prepared investment. The effect of the additives was evaluated from the color difference (deltaE*) between the as-cast surface and the polished surface of the cast specimen. B and Al were effective to prevent the blackening of a Type 4 gold alloy and the color of the as-cast surface approached that of the polished surface with increasing B and Al content. The prevention of the blackening of the gold alloy can be achieved by restraining the formation of CuO.

Surface textures of composite resins after combined wear test simulating both occlusal wear and brushing wear.

The purpose of this study was to investigate the relation between the texture of worn surfaces of composite resins and the maximum wear depth. Three types of composite resins were investigated: a hybrid composite resin consisting of irregular-shaped inorganic filler particles (APX); a composite resin which contained small, irregular-shaped, inorganic filler particles and large organic composite filler particles (SRE); and another which contained spherical inorganic filler particles and large organic composite filler (SDX). Surface profile measurement and elemental analysis were carried out on the worn surfaces of these three composite resins using an electron probe microanalyzer (EPMA). For the composite resin which exhibited the largest maximum wear depth, its surface texture was slightly rough with fine pores and grooves. For the composite resin with lowest maximum wear depth, it had a smooth worn surface due to the large organic composite filler being abraded during the combined wear test.