Anti-biofouling performance and microbial communities of an integrated fixed-film activated sludge membrane bioreactor with a fibrous carrier material: Pilot-scale demonstration.

Widespread use of membrane bioreactors for high-performance wastewater treatment depends on the prevention of biofouling during membrane filtration, which can reduce operating costs. Biofouling is usually prevented using mechanical and chemical membrane treatment methods, which can be time-consuming and expensive. In this study, we developed bio-capsules as a fluidizing carrier material in an integrated fixed-film activated sludge membrane bioreactor (IFAS-MBR). The bio-capsules were prepared from moniliform polyvinylidene chloride fibrous balls enclosed in a spherical plastic basket, and could harbor protozoa and metazoa. A pilot-scale anoxic-oxic IFAS-MBR system with a total volume of 132 m3 was operated to remove organic carbon and nitrogen from municipal wastewater at a high permeate flux (0.84 m3/m2/day). The efficacy of the bio-capsules and the prokaryotic/eukaryotic community structures in the system were investigated. After operation for 1 year, the system demonstrated stable removal of organic carbon (76.0 % ± 15.5 % as total organic carbon, 93.1 ± 5.3 % as BOD, and 88.5 ± 5.2 % as CODMn) and nitrogen (71.3 % ± 9.3 %) despite fluctuations in the influent concentrations. Increases in transmembrane pressure (TMP) were retarded from its increase rates from 0.56 kPa/day to 0.149-0.224 kPa/day by the bio-capsules, and the TMP was kept constant at around 20 kPa throughout the operational period. High-throughput sequencing of 16S rRNA gene amplicons showed that the prokaryotic family Pirellulaceae was metabolically active and correlated with the TMP. According to the 18S rRNA gene sequencing, the eukaryotic metazoan Bdelloidea was more abundant in the bio-capsules than in activated sludge, which was supported by microscopic observations. These results suggest that the application of bio-capsules prevents increases in the TMP by harboring the procaryotes and eukaryotes responsible for biofouling mitigation in the IFAS-MBR system.

A multicenter prospective cohort study on the effect of smoking cessation on periodontal therapies in Japan.

Few prospective studies have reported the effects of periodontal therapy on patients who attempted to quit smoking. This study aimed to assess how smoking cessation affects periodontal therapy. Twenty-five smokers with periodontitis were investigated by dividing them into two groups, a smoking cessation support group and a continued smoking group. Those in the support group received counseling and nicotine replacement therapy, followed by periodontal treatment conducted by dentists who had completed an e-learning course on smoking cessation. Clinical parameters were measured at baseline, 3, and 6 months. Most clinical parameters improved for those in the smoking cessation support group. There were no significant improvements in bleeding on probing (BOP) or the number of severe periodontal disease sites in the continued smoking group. Probing pocket depth (PPD) and clinical attachment levels (CAL) at sites that received scaling and root planing (SRP) significantly improved in all subjects. BOP did not improve at reevaluation in the smoking relapse subgroup. Patients in the smoking cessation support program led by dental professionals showed more improvement in BOP than those in the continued smoking group.

CO2 Laser De-epithelization Technique for Subepithelial Connective Tissue Graft: A Study of 21 Recessions.

BACKGROUND/AIM: To report cases in which we achieved sufficient width of the keratinized gingiva using a coronally advanced flap in combination with a subepithelial connective tissue graft (SCTG) obtained by the 'CO2 laser de-epithelization technique' (CODE). PATIENTS AND METHODS: Eleven patients with 21 Miller Class I, II, and III gingival recessions had surgery. To prepare SCTG, free gingival grafts were harvested and de-epithelialized extra-orally. De-epithelialization was conducted by irradiation of CO2 laser. Postoperative examinations were performed at 12 months. RESULTS: At 12 months, statistically highly significant root coverage was achieved in all recessions. Complete root coverage was obtained in 7 of the 21 recessions. The treatment yielded mean root coverage of 41.0%, and was associated with a mean gain of keratinized gingiva of 2.9±0.3 mm. CONCLUSION: The use of CODE allows harvesting grafts of excellent quality and quantity and increases the keratinization of the overlying mucosal epithelium.

A phenomenological reaction kinetic model for Cu removal from aqueous solutions by zero-valent iron (ZVI).

Zero-valent iron (ZVI) being an inexpensive and eco-friendly catalyst has drawn great attention in removal of heavy metals from wastewaters. However, quantitative understandings of ZVI processes are significantly deficient. To compensate for the lack of quantitative analyses of removal of heavy metals by ZVI, a phenomenological reaction kinetic model was newly developed for removal of Cu chosen as a typical heavy metal from acidic aqueous solutions by ZVI. The novel kinetic model is based on the adsorption of Cu2+ and H+ onto ZVI surface and subsequent Cu2+ reduction on ZVI surface and Fe2+ elution from ZVI. Batch experiments were conducted to elucidate effects of pH and Cu loading on Cu removal by ZVI in acidic aqueous solutions and to validate the proposed phenomenological reaction kinetic model. The quick and complete removals of 1.57 mM Cu were established in the rage of pH 2-5. Although the maximum Cu removal rate was obtained at pH 4, effects of pH were insignificant. In the range of Cu loading from 0.393 to 4.72 mM, almost complete Cu removals were obtained at pH 4 within 35 min. The changes in concentrations of Cu2+, Fe2+, H+ and dissolved oxygen were strongly linked with each other. They could be successfully simulated by the proposed model with the average correlation coefficient of 0.979. The capability of the phenomenological reaction kinetic model for dynamic simulation of Cu removal by ZVI under acidic conditions was confirmed.

A Scale-up Approach for Film Coating Process Based on Surface Roughness as the Critical Quality Attribute.

Scale-up approaches for film coating process have been established for each type of film coating equipment from thermodynamic and mechanical analyses for several decades. The objective of the present study was to establish a versatile scale-up approach for film coating process applicable to commercial production that is based on critical quality attribute (CQA) using the Quality by Design (QbD) approach and is independent of the equipment used. Experiments on a pilot scale using the Design of Experiment (DoE) approach were performed to find a suitable CQA from surface roughness, contact angle, color difference, and coating film properties by terahertz spectroscopy. Surface roughness was determined to be a suitable CQA from a quantitative appearance evaluation. When surface roughness was fixed as the CQA, the water content of the film-coated tablets was determined to be the critical material attribute (CMA), a parameter that does not depend on scale or equipment. Finally, to verify the scale-up approach determined from the pilot scale, experiments on a commercial scale were performed. The good correlation between the surface roughness (CQA) and the water content (CMA) identified at the pilot scale was also retained at the commercial scale, indicating that our proposed method should be useful as a scale-up approach for film coating process.

Evaluation of Fat Quantification in the Liver Using Dual Energy CT.

BACKGROUND AND PURPOSE: Recently, the number of patients with nonalcoholic fatty liver disease (NAFLD) has been increasing, and some of them progresses to cirrhosis and hepatocellular carcinoma. Dual energy CT allows the discrimination of substance using monochromatic image (MI), and steatosis exhibit specifically the CT value of each energy level. The purpose is to evaluate the fat quantification in the liver using spectral HU curve and CT value compare to a conventional image diagnosis. METHODS: Dual energy CT and liver biopsy were performed in 54 patients between October 2014 and April 2016. The CT value of 40 keV MI was measured by spectral HU curve setting 3 points ROI on the right and left liver. The CT value of 40 keV MI was compared with steatosis area and the NAFLD activity score (NAS). Additionally, steatosis area was compared with the conventional CT value scan and hepatorenal echo contrast value. RESULTS AND DISCUSSION: The CT value of 40 keV MI exhibited a negative correlation for the stenosis area (R2=0.619), and NAS (R2=0.147). Steatosis area exhibited correlation for the conventional CT value (R2=0.407), and hepatorenal echo contrast (R2=0.135). This study suggests that the evaluation of the fat quantification in the liver using the spectral HU curve and CT value improved in comparison to the conventional image diagnosis.

Quantitative Appearance Inspection for Film Coated Tablets.

The decision criteria for the physical appearance of pharmaceutical products are subjective and qualitative means of evaluation that are based entirely on human interpretation. In this study, we have developed a comprehensive method for the quantitative analysis of the physical appearance of film coated tablets. Three different kinds of film coated tablets with considerable differences in their physical appearances were manufactured as models, and their surface roughness, contact angle, color measurements and physicochemical properties were investigated as potential characteristics for the quantitative analysis of their physical appearance. All of these characteristics were useful for the quantitative evaluation of the physical appearances of the tablets, and could potentially be used to establish decision criteria to assess the quality of tablets. In particular, the analysis of the surface roughness and film coating properties of the tablets by terahertz spectroscopy allowed for an effective evaluation of the tablets' properties. These results indicated the possibility of inspecting the appearance of tablets during the film coating process.

Three-layered architecture of the popliteal fascia that acts as a kinetic retinaculum for the hamstring muscles.

When patients report pain in the popliteal fossa upon knee extension, the pain is usually localized in the lower region of the popliteal fossa. However, some patients complain of pain in the upper region of the popliteal fossa as the knee is flexed, which motivated us to examine the role of the popliteal fascia as the retinaculum of the hamstring muscles. Thirty-four thighs from 19 Japanese cadavers were dissected. The popliteal fascia was defined as the single aponeurotic sheet covering the popliteal fossa. We found that the fascia acted as a three-layered retinaculum for the flexor muscles of the thigh and provided a secure route for neurovascular structures to the lower leg in any kinetic position of the knee joint. The superficial layer of the popliteal fascia covering the thigh was strongly interwoven with the epimysium of biceps femoris along its lateral aspect and with that of the semimembranosus along its medial aspect, ensuring that the flexor muscles remained in their correct positions. The intermediate layer arose from the medial side of biceps femoris and merged medially with the superficial layer. The profound layer stretched transversely between the biceps femoris and the semimembranosus. Moreover, we investigated the nerve distribution in the popliteal fascia using Sihler's staining and whole-mount immunostaining for neurofilaments. The three-layered fascia was constantly innervated by branches from the posterior femoral cutaneous or saphenous nerve. The nerves were closely related and distributed to densely packed collagen fibers in the superficial layer as free or encapsulated nerve endings, suggesting that the fascia is involved in pain in the upper region of the popliteal fossa.

Application of terahertz pulse imaging as PAT tool for non-destructive evaluation of film-coated tablets under different manufacturing conditions.

Film-coated tablets (FCTs) are a popular solid dosage form in pharmaceutical industry. Manufacturing conditions during the film-coating process affect the properties of the film layer, which might result in critical quality problems. Here, we analyzed the properties of the film layer using a non-destructive approach with terahertz pulsed imaging (TPI). Hydrophilic tablets that become distended upon water absorption were used as core tablets and coated with film under different manufacturing conditions. TPI-derived parameters such as film thickness (FT), film surface reflectance (FSR), and interface density difference (IDD) between the film layer and core tablet were affected by manufacturing conditions and influenced critical quality attributes of FCTs. Relative standard deviation of FSR within tablets correlated well with surface roughness. Tensile strength could be predicted in a non-destructive manner using the multivariate regression equation to estimate the core tablet density by film layer density and IDD. The absolute value of IDD (Lateral) correlated with the risk of cracking on the lateral film layer when stored in a high-humidity environment. Further, in-process control was proposed for this value during the film-coating process, which will enable a feedback control system to be applied to process parameters and reduced risk of cracking without a stability test.

[Usefulness of the Training of Trigger Point in Coronary CT Using Test Bolus Tracking Method].

BACKGROUND: Test bolus tracking (TBT) method has been used in coronary CT examination, because it is possible to examine the optimum contrast timing. However, the scan timing highly depends on an operators' recognition of peak in test bolus, thus there is a possibility of variation in contrast effect. PURPOSE: The aim of this study is to improve the variation of contrast effect among the operators. METHODS: The training for the operators was conducted to acknowledge them the optimal trigger points. The mean CT value and standard deviation of the ascending aorta were calculated to compare before and after the training. RESULTS: The mean CT value of the ascending aorta after the training was 485.02±73.06 HU, compared to 462.53±78.26 HU before the training. Standard deviation was significantly lower than before the training. CONCLUSION: The variation of contrast effect between the operators has been reduced by the training, and reproducibility of the examination has been improved.

Simultaneous removal of nitrate, hydrogen peroxide and phosphate in semiconductor acidic wastewater by zero-valent iron.

The zero-valent iron (ZVI) wastewater treatment has been applied to simultaneous removal of nitrate, hydrogen peroxide and phosphate in semiconductor acidic wastewaters. The simultaneous removal occurs by the reactions performed due to the sequential transformation of ZVI under the acidic condition. Fortunately the solution pH of semiconductor acidic wastewaters is low which is effective for the sequential transformation of ZVI. Firstly the reduction of nitrate is taken place by electrons generated by the corrosion of ZVI under acidic conditions. Secondly the ferrous ion generated by the corrosion of ZVI reacts with hydrogen peroxide and generates ·OH radical (Fenton reaction). The Fenton reaction consists of the degradation of hydrogen peroxide and the generation of ferric ion. Finally phosphate precipitates out with iron ions. In the simultaneous removal process, 1.6 mM nitrate, 9.0 mM hydrogen peroxide and 1.0 mM phosphate were completely removed by ZVI within 100, 15 and 15 min, respectively. The synergy among the reactions for the removal of nitrate, hydrogen peroxide and phosphate was found. In the individual pollutant removal experiment, the removal of phosphate by ZVI was limited to 80% after 300 min. Its removal rate was considerably improved in the presence of hydrogen peroxide and the complete removal of phosphate was achieved after 15 min.

Applying terahertz technology for nondestructive detection of crack initiation in a film-coated layer on a swelling tablet.

Here, we describe a nondestructive approach using terahertz wave to detect crack initiation in a film-coated layer on a drug tablet. During scale-up and scale-down of the film coating process, differences in film density and gaps between the film-coated layer and the uncoated tablet were generated due to differences in film coating process parameters, such as the tablet-filling rate in the coating machine, spray pressure, and gas-liquid ratio etc. Tablets using the PEO/PEG formulation were employed as uncoated tablets. We found that heat and humidity caused tablets to swell, thereby breaking the film-coated layer. Using our novel approach with terahertz wave nondestructively detect film surface density (FSD) and interface density differences (IDDs) between the film-coated layer and an uncoated tablet. We also found that a reduced FSD and IDD between the film-coated layer and uncoated tablet increased the risk of crack initiation in the film-coated layer, thereby enabling us to nondestructively predict initiation of cracks in the film-coated layer. Using this method, crack initiation can be nondestructively assessed in swelling tablets after the film coating process without conducting accelerated stability tests, and film coating process parameters during scale-up and scale-down studies can be appropriately established.

Profile of new green fluorescent protein transgenic Jinhua pigs as an imaging source.

Animal imaging sources have become an indispensable material for biological sciences. Specifically, gene-encoded biological probes serve as stable and high-performance tools to visualize cellular fate in living animals. We use a somatic cell cloning technique to create new green fluorescent protein (GFP)-expressing Jinhua pigs with a miniature body size, and characterized the expression profile in various tissues/organs and ex vivo culture conditions. The born GFP-transgenic pig demonstrate an organ/tissue-dependent expression pattern. Strong GFP expression is observed in the skeletal muscle, pancreas, heart, and kidney. Regarding cellular levels, bone-marrow-derived mesenchymal stromal cells, hepatocytes, and islet cells of the pancreas also show sufficient expression with the unique pattern. Moreover, the cloned pigs demonstrate normal growth and fertility, and the introduced GFP gene is stably transmitted to pigs in subsequent generations. The new GFP-expressing Jinhua pigs may be used as new cellular/tissue light resources for biological imaging in preclinical research fields such as tissue engineering, experimental regenerative medicine, and transplantation.

The influence of living donor liver transplantation on families with or without siblings.

With child living donor liver transplantation (LDLT), two people from one family, a child patient and one parent and one parent are forced to be hospitalized, so the family faces very servere problems. This is especially severe in cases when pediatric patients have siblings. Our research investigated the influence of LDLT upon families with siblings as compared to those without, especially the impact of surgery and hospitalization on family relationships. Families with siblings had more stress about child care and they tended to be more anxious about child development. The siblings had a lot of stress and mental problems. Therefore, the families of LDLT are seen to need special supports, especially those who had siblings.

Influence of fillers in powder formulations containing N-acetyl-L-cysteine on nasal peptide absorption.

We examined the influence of filler species on the nasal absorbability of peptide drugs via a newly developed powdery formulation system containing N-acetyl-l-cysteine (NAC) as an absorption enhancer. Using salmon calcitonin (SCT) as the principal model drug, we tested the effects of various formulations with different powder materials as fillers on the nasal absorption of SCT in rats. An intranasal administration experiment revealed that the use of less wettable powders provided better nasal absorbability, and the highest absolute bioavailability (30.0% +/- 8.6%) was obtained when ethylcellulose was used as a filler. All these results were readily explicable in terms of our hypothetical enhancing mechanism. Furthermore, human parathyroid hormone and insulin were applied to this ethylcellulose formulation system, giving nasal bioavailabilities of 28.2% +/- 6.5% and 23.4% +/- 10.6%, respectively, thus suggesting that this formulation system is widely applicable to peptide drugs.

Improved nasal absorption of salmon calcitonin by powdery formulation with N-acetyl-L-cysteine as a mucolytic agent.

To establish a new formulation technology for the nasal delivery of peptide and protein drugs, we examined whether a mucolytic agent, N-acetyl-L-cysteine (NAC), could enhance the nasal absorption of a powder form of salmon calcitonin, a model peptide drug. We used ethylcellulose as an inert water-insoluble excipient. Various test formulations were prepared, and the effects on nasal absorbability were evaluated in rats and dogs. The powder formulation with NAC gave significant nasal absorption of SCT in both animal models, with absolute bioavailabilities of 30.0% in rats and 24.9% in dogs. Also, nasal administration of this formulation gave a quicker absorption rate than subcutaneous administration of SCT. NAC may reduce nasal fluid viscocity and improve accessibility of the drug to the epithelial membrane. The powder SCT/NAC/ethylcellulose formulation did not induce irritation or histological damage to the nasal membrane in rabbits. These results suggest that this formulation technology may be widely applicable for the nasal delivery of peptide or protein drugs.

Development of manufacturing method for rapidly disintegrating oral tablets using the crystalline transition of amorphous sucrose.

The industrial manufacturing of rapidly disintegrating oral tablets with a sufficient tensile strength was investigated. The manufacturing method of the tablets involved the crystalline transition of amorphous sucrose that was produced in the process of fluidized bed granulation of mannitol using sucrose solution as a binder. The aim of this article was to clarify the usefulness of amorphous sucrose formed during the granulation for the rapidly disintegrating oral tablets manufacturing, and to investigate the effects of crystalline transition of the amorphous sucrose in granules on the characteristics of the resultant tablets prepared by this crystalline transition (CT) method. The X-ray diffraction measurement and thermal analysis showed that amorphous sucrose was effectively formed in granules consisting of 95% mannitol and 5% sucrose when the granulation was performed on the condition of water content of 4%. The tensile strength of tablets comprised of the granules, which were compressed before the crystallization of amorphous sucrose, increased remarkably after storage, because new internal solid bridges were formed in the tablets as a result of the crystallization. We conclude that rapidly disintegrating oral tablets can effectively be manufactured by the CT method using the granules obtained by the fluidized bed granulation method.

Synergistic absorption enhancement of salmon calcitonin and reversible mucosal injury by applying a mucolytic agent and a non-ionic surfactant.

The present study investigated the intestinal absorption enhancement of salmon calcitonin (SCT) and the intestinal mucosal damage when a mucolytic agent and a non-ionic surfactant were administered simultaneously to rats. N-acetylcysteine (NAC) and p-t-octyl phenol polyoxyethylene-9.5 (Triton X -100, TX-100) were chosen as the model mucolytic agent and the non-ionic surfactant, respectively. Dosing solutions containing these agents were administered directly into the rat jejunum, and the bioavailability of SCT up to 2 h was determined. NAC and TX-100, when they were used alone at a dose of 1 mg/head, did not show the apparent enhancement compared to the control. However, simultaneous use of NAC and TX-100 enhanced the intestinal absorption of SCT in a synergistic manner, and absolute bioavailability increased 12.5-fold compared to the control. The effect of NAC and TX-100 on SCT absorption was not dependent on their doses over the range of 0.2-2 mg/head, and the maximum effect was obtained at a dose of 1mg/head. Absorption enhancement of SCT by a combination of NAC and TX-100 was compared to those from the classical absorption enhancers. Absorption-enhancing ability of the combination of NAC and TX-100 was significantly higher than those of sodium deoxycholate, citrate, and the combination of citrate and taurocholate, and was comparable with that of the combination of citrate and taurodeoxycholate. Finally, the intestinal mucosal damage caused by the combination of NAC and TX-100 was assessed using a capsule device. Acute damage on intestinal mucosa was observed when they were exposed into rat intestine, but this morphological damage was found to be reversible. All these results suggest that simultaneous use of a mucolytic agent and a non-ionic surfactant would offer a potentiality for peroral delivery of peptide drugs like SCT.

Effect of formulated ingredients on rapidly disintegrating oral tablets prepared by the crystalline transition method.

The aim of this article was to determine the optimal ingredients for the rapidly disintegrating oral tablets prepared by the crystalline transition method (CT method). The effect of ingredients (diluent, active drug substance and amorphous sugar) on the characteristics of the tablets was investigated. The ingredients were compressed and the resultant tablets were stored under various conditions. The oral disintegration time of the tablet significantly depended on diluents, due to differences in the penetration of a small amount of water in the mouth and the viscous area formed inside the tablet. The oral disintegration time was 10-30 s for tablets with a tensile strength of approximately 1 MPa, when erythritol, mannitol or xylitol was used as the diluent. The increase in the tensile strength of tablets containing highly water-soluble active drug substances during storage was as large as that of tablets without active drug substances, while the increase in the tensile strength of tablets containing low water-soluble active drug substances was small. It was therefore found that highly water-soluble active drug substances were more suitable for the formulation prepared by the CT method than low water-soluble active drug substances. Irrespective of the type of amorphous sugar (amorphous sucrose, lactose or maltose) used, the porosity of tablets with 1 MPa of tensile strength was 30-40%, and their oral disintegration time was 10-20 s. The optimal ingredients for rapidly disintegrating oral tablets with reasonable tensile strength and disintegration time were therefore determined from these results.