Experimental Study on Sand Stabilization Using Bio-Cementation with Wastepaper Fiber Integration.

Recently, green materials and technologies have received considerable attention in geotechnical engineering. One of such techniques is microbially-induced carbonate precipitation (MICP). In the MICP process, CaCO3 is achieved bio-chemically within the soil, thus enhancing the strength and stiffness. The purpose of this study is to introduce the wastepaper fiber (WPF) onto the MICP (i) to study the mechanical properties of MICP-treated sand with varying WPF content (0-8%) and (ii) to assess the freeze-thaw (FT) durability of the treated samples. Findings revealed that the ductility of the treated samples increases with the increase in WPF addition, while the highest UCS is found with a small fiber addition. The results of CaCO3 content suggest that the WPF addition enhances the immobilization of the bacteria cells, thus yielding the precipitation content. However, shear wave velocity analysis indicates that a higher addition of WPF results in rapid deterioration of the samples when subjected to freeze-thaw cycles. Microscale analysis illuminates that fiber clusters replace the solid bonding at particle contacts, leading to reduced resistance to freeze-thaw damage. Overall, the study demonstrates that as a waste material, WPF could be sustainably reused in the bio-cementation.

Tumor-targeting Salmonella typhimurium A1-R overcomes nab-paclitaxel resistance in a cervical cancer PDOX mouse model.

PURPOSE: Cervical cancer is a recalcitrant disease. To help overcome this problem, we previously established a patient-derived orthotopic xenograft (PDOX) model of cervical cancer. In the previous study, we found the tumor to be resistant to nab-paclitaxal (nab-PTX). We also previously developed the tumor-targeting bacteria Salmonella typhimurium A1-R (S. typhimurium A1-R). The aim of the present study was to investigate the efficacy of S. typhimurium A1-R to overcome nab-PTX resistance in the cervical cancer PDOX model. METHODS: Cervical-cancer tumor fragments were implanted orthotopically into the neck of the uterus of nude mice. The cervical-cancer PDOX models were randomized into the following four groups after the tumor volume reached 60 mm3: G1: untreated group; G2: nab-PTX (i.v., 10 mg/kg, biweekly, 3 weeks); G3: Salmonella typhimurium A1-R (i.v., 5 × 107 CFU/body, weekly, 3 weeks); G4: nab-PTX combined with Salmonella typhimurium A1-R (nab-PTX, 10 mg/kg, i.v., biweekly, 3 weeks; S. typhimurium A1-R, 5 × 107 CFU/body, i.v., weekly, 3 weeks). Each group comprised eight mice. All mice were sacrificed on day 22. Tumor volume was measured on day 0 and day 22. Body weight was measured twice a week. RESULTS: Nab-PTX and Salmonella typhimurium A1-R did not show significant efficacy as monotherapy compared to the control group (P = 0.564 and P = 0.120, respectively). In contrast, nab-PTX combined with Salmonella typhimurium A1-R significantly suppressed tumor growth compared to the untreated control group and nab-PTX group (P < 0.001 and P = 0.026, respectively). CONCLUSIONS: Salmonella typhimurium A1-R has potential future clinical application to overcome drug resistance in cervical cancer.

Investigating toxicity specific to adjuvanted vaccines.

In an attempt to understand the unique toxicity of adjuvanted vaccines, we studied how toxicity develops over time following vaccine administration. In addition to on- and off-target toxicity typically observed with general pharmaceuticals, we observed toxicity associated with both the generation and the broad action of effectors (antibodies and/or cytotoxic T lymphocytes, CTLs). The impact on effector generation appears to be related to local tolerance specific to the adjuvant. The vaccine immune response by effectors serves to demonstrate species relevance as outlined in the recent WHO guideline on the nonclinical evaluation of adjuvanted vaccines. When regarded as pharmaceuticals that function at sites of local administration, adjuvants have inherent on- and off-target toxicity. On-target toxicity of the adjuvant is typically associated with effector generation, and could vary depending on animal species. Therefore, the use of species with sensitivity to adjuvants described in the WHO guidelines is required to evaluate the toxicity of the vaccine associated with effector generation. Changes in safety pharmacology endpoints would be considered off-target and further studies are conducted only if changes in these endpoints are observed in nonclinical or clinical studies. Thus our decision tree does not recommend the routine conduct of stand-alone safety pharmacology studies.

Cervical Cancer Patient-Derived Orthotopic Xenograft (PDOX) Is Sensitive to Cisplatinum and Resistant to Nab-paclitaxel.

BACKGROUND: Cervical cancer is a world-wide problem that requires transformative therapeutic strategies. We have previously developed patient-derived orthotopic xenograft (PDOX) nude-mouse models of this disease. In the present report, we demonstrate that the standard drug, cisplatinum (CDDP), is highly-effective while the new, highly-touted agent, nab-paclitaxel (NAB-PTX) is ineffective. MATERIALS AND METHODS: Cervical PDOX tumors were grown on the cervix of nude mice for 4 weeks after surgical orthotopic implantation (SOI). Tumors were treated with CDDP or NAB-PTX. RESULTS: H&E staining demonstrated that the PDOX tumor recapitulated the original patient tumor. CDDP was highly-effective. One tumor that was treated with CDDP completely regressed. CDDP-treated tumors were smaller (tumor volume ratio: 0.42±0.36) than the control group (tumor volume ratio: 3.47±1.66) (p<0.01). In contrast, NAB-PTX did not show significant efficacy on the cervical cancer PDOX model (tumor volume ratio: 2.85±1.45) (p=0.47). CDDP-treated tumor weight (50±50 mg) was significantly less than control (238±114 mg) (p<0.01). NAB-PTX-treated tumors were not reduced in weight (246±136 mg) compared to control (p=0.91). There were no significant differences in mouse body weight between groups. Histological evaluation demonstrated that CDDP-treated tumors were fibrotic with scattered squamous cell nests compared to control or NAB-PTX-treated tumors. CONCLUSION: The results of the present study demonstrate the power of PDOX models of cervical cancer to distinguish efficacy of potential therapeutics for individual patients with this disease.

Remembering and forgetting: directed forgetting effect in obsessive-compulsive disorder.

It has been reported that episodic memory seems to be impaired in patients with obsessive-compulsive disorder (OCD) because the patients repeat a specific checking behavior, but it is still unknown if OCD patients show memory impairments associated with their unique symptoms or not. To study episodic memory in OCD patients, we examined the directed forgetting effect. Patients with OCD and healthy control participants were given a list of 24 emotionally neutral everyday words (12 remember [R]-cued words and 12 forget [F]-cued words) under two conditions: List and Item. The results of our study showed that OCD patients recalled a number of F-cued words similar to that for controls and relatively fewer R-cued words than controls under both List and Item conditions. Consequently, the directed forgetting effect was smaller in OCD patients than controls. Our results demonstrated that both selective encoding and retrieval inhibition processes are impaired in OCD, and we suggest that recall of unfavorable items to be forgotten intruded into necessary items to be remembered. This impairment in episodic memory may partially account for some of the unique clinical symptoms of OCD.

Factors of error and effort in memory intervention for patients with Alzheimer's disease and amnesic syndrome.

BACKGROUND: Factors of error and effort in study conditions play a crucial role in the intervention for memory-impaired individuals. In the present study, efficacy of four study conditions was compared in order to elucidate the optimal study conditions: errorless/errorful and effortless/effortful. METHODS: A total of 18 patients with Alzheimer's disease and 12 patients with amnesic syndrome received study-test sessions under four different study conditions: errorless/errorful and effortless/effortful. RESULTS: The errorless learning advantage was confirmed for both Alzheimer's disease and amnesic syndrome on both free recall and cued recall tests. In contrast, effortful learning was effective only for amnesic syndrome on a free recall test. CONCLUSION: Despite the overall advantage of errorless learning, the effortful process was effective in circumscribed situations.

Further evidence for a comparable memory advantage of self-performed tasks in Korsakoff's syndrome and nonamnesic control subjects.

Two experiments were carried out to examine memory in persons with amnesia using self-performed tasks. In Experiment 1, persons with Korsakoff's syndrome and nonamnesic participants with alcoholism learned action phrases not involving real objects by either self-performed tasks or verbal tasks. As indexed by free recall and recognition tests, a memory advantage favoring self-performed tasks was confirmed in both participant groups. In Experiment 2, persons with Korsakoff's syndrome, nonamnesic alcoholic participants, and young control participants learned object names under three different study conditions that differed from one another as to whether actions for each name were verbally generated and whether actions actually were performed. Verbal generation with or without performing the action facilitated recognition, whereas recall advantage was found only in the verbal generation-plus performance condition. These findings confirm a comparable memory advantage of self-performed tasks for a group with Korsakoff's syndrome and a group of nonamnesic comparison participants. Action memory therefore has potential therapeutic implications for memory rehabilitation.

Cross-script and within-script priming in alcoholic Korsakoff patients.

In two experiments, alcoholic Korsakoff patients and control subjects studied a list of Japanese nouns written in either Hiragana or Kanji script. Word-fragment completion and recognition tests were then administered in Hiragana. When the writing script was changed between study and test phases, repetition priming in word-fragment completion was significantly attenuated but was still reliable against baseline performance. This was confirmed for both Korsakoff patients and control subjects. In contrast, the script change had little effect on recognition memory, which was severely impaired in Korsakoff patients. The results suggest that repetition priming is mediated by two different implicit processes, one that is script-specific and the other that is assumed to operate at a more abstract level.