Morphology and release kinetics of protein-loaded porous poly(L-lactic acid) spheres prepared by freeze-drying technique

Freeze-drying a biodegradable polymer, poly(L-lactic acid) (PLLA) from 1,4-dioxane solutions provided very porous spherical particles of ca. 3 mm in radius with specific surface area of 8 − 13 m2 g−1. The surface of the particle was found to be less porous compared with its interior. To apply the freeze-dried PLLA (FDPLLA) to drug delivery system, its morphology and drug releasing kinetics were investigated, bovine serum albumin (BSA) being used as a model drug compound. Immersion of FDPLLA into a BSA aqueous solution gave BSA-loaded FDPLLA, where mass fraction of the adsorbed BSA reached up to 79%. Time-dependent release profile of BSA in water suggested a two-step mechanism: (1) very rapid release of BSA deposited on and near the particle surface, which results in an initial burst, and (2) leaching of BSA from the interior of the particle by the diffusion process. It was suggested that the latter process is largely governed by the surface porosity. The porosity of both the interior and surface was found to decrease remarkably as the concentration of the original PLLA / 1,4-dioxane solution increases, C0. Thus, C0 is a key parameter that controls the loading and releasing of BSA

National seroepidemiological study of COVID-19 after the initial rollout of vaccines: Before and at the peak of the Omicron-dominant period in Japan

BACKGROUND: Based on routine surveillance data, Japan has been affected much less by COVID-19 compared with other countries. To validate this, we aimed to estimate SARS-CoV-2 seroprevalence and examine sociodemographic factors associated with cumulative infection in Japan. METHODS: A population-based serial cross-sectional seroepidemiological investigation was conducted in five prefectures in December 2021 (pre-Omicron) and February-March 2022 (Omicron [BA.1/BA.2]-peak). Anti-nucleocapsid and anti-spike antibodies were measured to detect infection-induced and vaccine/infection-induced antibodies, respectively. Logistic regression was used to identify associations between various factors and past infection. RESULTS: Among 16 296 participants (median age: 53 [43-64] years), overall prevalence of infection-induced antibodies was 2.2% (95% CI: 1.9-2.5%) in December 2021 and 3.5% (95% CI: 3.1-3.9%) in February-March 2022. Factors associated with past infection included those residing in urban prefectures (Tokyo: aOR 3.37 [95% CI: 2.31-4.91], Osaka: aOR 3.23 [95% CI: 2.17-4.80]), older age groups (60s: aOR 0.47 [95% CI 0.29-0.74], 70s: aOR 0.41 [95% CI 0.24-0.70]), being vaccinated (twice: aOR 0.41 [95% CI: 0.28-0.61], three times: aOR 0.21 [95% CI: 0.12-0.36]), individuals engaged in occupations such as long-term care workers (aOR: 3.13 [95% CI: 1.47-6.66]), childcare workers (aOR: 3.63 [95% CI: 1.60-8.24]), food service workers (aOR: 3.09 [95% CI: 1.50-6.35]), and history of household contact (aOR: 26.4 [95% CI: 20.0-34.8]) or non-household contact (aOR: 5.21 [95% CI:3.80-7.14]) in February-March 2022. Almost all vaccinated individuals (15 670/15 681) acquired binding antibodies with higher titers among booster dose recipients. CONCLUSIONS: Before Omicron, the cumulative burden was >10 times lower in Japan (2.2%) compared with the US (33%), the UK (25%), or global estimates (45%), but most developed antibodies owing to vaccination

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Acute Effect of Metformin on Postprandial Hypertriglyceridemia through Delayed Gastric Emptying

Postprandial hypertriglyceridemia is a potential target for cardiovascular disease prevention in patients with diabetic dyslipidemia. Metformin has been reported to reduce plasma triglyceride concentrations in the postprandial states. However, little is known about the mechanisms underlying the triglyceride-lowering effect of metformin. Here, we examined the effects of metformin on lipid metabolism after olive oil-loading in 129S mice fed a high fat diet for three weeks. Metformin administration (250 mg/kg) for one week decreased postprandial plasma triglycerides. Pre-administration (250 mg/kg) of metformin resulted in a stronger triglyceride-lowering effect (approximately 45% lower area under the curve) than post-administration. A single administration (250 mg/kg) of metformin lowered plasma postprandial triglycerides comparably to administration for one week, suggesting an acute effect of metformin on postprandial hypertriglyceridemia. To explore whole body lipid metabolism after fat-loading, stomach size, fat absorption in the intestine, and fat oxidation (13C/12C ratio in expired CO2 after administration of glyceryl-1-13C tripalmitate) were measured with and without metformin (250 mg/kg) pre-treatment. In metformin-treated mice, larger stomach size, lower fat oxidation, and no change in lipid absorption were observed. In conclusion, metformin administration before fat loading reduced postprandial hypertriglyceridemia, most likely by delaying gastric emptying

Children with flat feet have weaker toe grip strength than those having a normal arch.

[Purpose] This study investigated the relationship between toe grip strength and foot posture in children. [Subjects and Methods] A total of 619 children participated in this study. The foot posture of the participants was measured using a foot printer and toe grip strength was measured using a toe grip dynamometer. Children were classified into 3 groups; flatfoot, normal, and high arch, according to Staheli's arch index. The differences in demographic data and toe grip strength among each foot posture group were analyzed by analysis of variance. Additionally, toe grip strength differences were analyzed by analysis of covariance, adjusted to body mass index, age, and gender. [Results] The number of participants classified as flatfoot, normal, and high arch were 110 (17.8%), 468 (75.6%), and 41 (6.6%), respectively. The toe grip strength of flatfoot children was significantly lower than in normal children, as shown by both analysis of variance and analysis of covariance. [Conclusion] A significant difference was detected in toe grip strength between the low arch and normal foot groups. Therefore, it is suggested that training to increase toe grip strength during childhood may prevent the formation of flat feet or help in the development of arch

Association between forefoot pain and sesamoid rotation angle determined using a weight-bearing plantar ultrasound imaging device

Forefoot pain is a common symptom for several foot problems. This study aimed to determine whether parameters of forefoot structure (hallux valgus angle (HVA), transverse arch height (TAH) and sesamoid rotation angle (SRA)) are associated with forefoot pain. 547 feet of adult women were divided into two groups: without pain (n = 472) and with pain (n = 75). HVA was measured with a goniometer, TAH and SRA were measured using a weight bearing plantar ultrasound imaging device.Associations between forefoot pain and parameters of forefoot structure were analyzed using the Mann-Whitney U test and univariate and multivariate logistic regression analyses. The intra-rater and inter-rater reliability of the ultrasound images were also tested. SRA was significantly greater in the group with pain compared to the group without pain (p = 0.031) but not HVA (p = 0.057) nor TAH (p = 0.117). The association between forefoot pain and SRA was significant (univariate: p = 0.015 and multivariate p = 0.015), but not between HVA nor TAH. The intra-rater and inter-rater reliability were almost perfect (SRA: ICC1, 1 = 0.94, ICC2, 1 = 0.91 and TAH: ICC1, 1 = 0.88, ICC2, 1 = 0.81). We conclude that a higher SRA is related to forefoot pain and should be taken into consideration for assessment of patients with forefoot pain