Best-Fit Circle for the Replication of Humeral Head Anatomy in Total Shoulder Arthroplasty.

Background: Anatomic restoration of the humeral head is critical for successful shoulder replacement. Accurate measurements of the humeral head are essential for anatomic substitution. Purpose: To evaluate whether a best-fit circle of the humeral head, as determined from different projections of plain radiographs, can predict the humeral head implant size for either the left or right shoulder. Study Design: Descriptive laboratory study. Methods: Bilateral shoulder radiographs of 200 patients without arthropathy or other abnormal findings of the humeral head were evaluated. The best-fit circle was obtained based on 3 points: the medial and lateral endpoints of the anatomic neck and the lateral cortex below the greater tuberosity. This circle was drawn on 5 different radiographic projections (shoulder anteroposterior [AP], glenoid AP, outlet, axillary, and 30° caudal tilt) of the left and right shoulders of each patient, and the radius of each circle was measured. Agreement in the best-fit circle radius between the left and right shoulders was statistically analyzed using the intraclass correlation coefficient (ICC). There were 2 independent blinded observers who performed each measurement twice to evaluate inter- and intraobserver reliability. Results: Overall agreement in the radius between the right and left shoulders was excellent (all ICCs ≥0.990). The ICCs according to the radiographic view were 0.990 (95% CI, 0.986-0.993) for shoulder AP, 0.992 (95% CI, 0.989-0.995) for glenoid AP, 0.996 (95% CI, 0.994-0.997) for outlet, 0.994 (95% CI, 0.991-0.996) for axillary, and 0.993 (95% CI, 0.990-0.995) for 30° caudal tilt. Interobserver ICCs demonstrated a high level of precision: 0.987 (95% CI, 0.978-0.993) for shoulder AP, 0.986 (95% CI, 0.974-0.992) for glenoid AP, 0.974 (95% CI, 0.954-0.985) for outlet, 0.991 (95% CI, 0.984-0.995) for axillary, and 0.987 (95% CI, 0.977-0.993) for 30° caudal tilt. Intraobserver ICCs demonstrated excellent test-retest reliability: 0.983 (95% CI, 0.970-0.991) for shoulder AP, 0.989 (95% CI, 0.980-0.994) for glenoid AP, 0.987 (95% CI, 0.978-0.993) for outlet, 0.985 (95% CI, 0.973-0.991) for axillary, and 0.970 (95% CI, 0.947-0.983) for 30° caudal tilt. Conclusion: The best-fit circle to calculate the ideal size of a humeral head implant was able to be determined from different projections of plain radiographs. Clinical Relevance: Anatomic restoration of a deformed humeral head can be achieved using the best-fit circle of the contralateral humeral head as obtained from plain radiographs. This method can facilitate preoperative planning and postoperative evaluation in the anatomic restoration of the shoulder to avoid the problems of overstuffing.

Cubitus varus after pediatric lateral condylar fracture: true or pseudo?

PURPOSE: Common complications of lateral condylar fractures are lateral condylar overgrowth, lateral bony spur and cubitus varus. Lateral condylar overgrowth or lateral bony spur may appear as cubitus varus on gross examination. Such gross cubitus varus without actual angulation is pseudo-cubitus varus, while a difference of more than 5° in varus angulation on X-ray is true cubitus varus. This study aimed to compare true and pseudo-cubitus varus. METHODS: One hundred ninety-two children treated for unilateral lateral condylar fracture with a follow-up period of over six months were included. The Baumann angle, humerus-elbow-wrist angle and interepicondylar width of both side were compared. More than 5° in varus angulation on X-ray was considered cubitus varus. Increase in interepicondylar width was considered lateral condylar overgrowth or a lateral bony spur. The risk factors that could predict the development of a true cubitus varus were analyzed. RESULTS: True cubitus varus was 32.8%, measured by Baumann angle and 29.2%, measured by humerus-elbow-wrist angle. A total of 94.8% of patients showed an increased interepicondylar width. The predicted cut-off value for 5° varus angulation on the Baumann angle was a 3.675 mm increase in interepicondylar width by ROC curve analysis. The risk of cubitus varus in stage 3, 4, and 5 fractures according to Song's classification was 2.88 times higher than that in stage 1 and 2 fractures on multivariable logistic regression analysis. CONCLUSION: Pseudo-cubitus varus is more prevalent than true cubitus varus. A 3.7 mm increase in interepicondylar width could simply predict true cubitus varus. The risk of cubitus varus increased in Song's classification stages 3, 4, and 5.

Searching for Novel Candidate Small Molecules for Ameliorating Idiopathic Pulmonary Fibrosis: a Narrative Review.

Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)-ß-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

Regulation of the Gene Expression of Airway MUC5AC Mucin through NF-κB Signaling Pathway by Artesunate, an Antimalarial Agent.

In this study, artesunate, an antimalarial agent, was investigated for its potential effect on the gene expression of airway MUC5AC mucin. The human pulmonary epithelial NCI-H292 cells were pretreated with artesunate for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of artesunate on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also examined. Artesunate inhibited the glycoprotein production and mRNA expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest artesunate suppresses the gene expression of mucin through regulation of NF-kB signaling pathway, in human pulmonary epithelial cells.

Pitavastatin Induces Apoptosis of Cutaneous Squamous Cell Carcinoma Cells through Geranylgeranyl Pyrophosphate-Dependent c-Jun N-Terminal Kinase Activation.

BACKGROUND: Pitavastatin is a cholesterol-lowering drug and is widely used clinically. In addition to this effect, pitavastatin has shown the potential to induce apoptosis in cutaneous squamous cell carcinoma (SCC) cells. OBJECTIVE: The purpose of this study is to investigate the effects and possible action mechanisms of pitavastatin. METHODS: SCC cells (SCC12 and SCC13 cells) were treated with pitavastatin, and induction of apoptosis was confirmed by Western blot. To examine whether pitavastatin-induced apoptosis is related to a decrease in the amount of intermediate mediators in the cholesterol synthesis pathway, the changes in pitavastatin-induced apoptosis after supplementation with mevalonate, squalene, geranylgeranyl pyrophosphate (GGPP) and dolichol were investigated. RESULTS: Pitavastatin dose-dependently induced apoptosis of cutaneous SCC cells, but the viability of normal keratinocytes was not affected by pitavastatin at the same concentrations. In supplementation experiments, pitavastatin-induced apoptosis was inhibited by the addition of mevalonate or downstream metabolite GGPP. As a result of examining the effect on intracellular signaling, pitavastatin decreased Yes1 associated transcriptional regulator and Ras homolog family member A and increased Rac family small GTPase 1 and c-Jun N-terminal kinase (JNK) activity. All these effects of pitavastatin on signaling molecules were restored when supplemented with either mevalonate or GGPP. Furthermore, pitavastatin-induced apoptosis of cutaneous SCC cells was inhibited by a JNK inhibitor. CONCLUSION: These results suggest that pitavastatin induces apoptosis of cutaneous SCC cells through GGPP-dependent JNK activation.

Meclofenamate Suppresses MUC5AC Mucin Gene Expression by Regulating the NF-kB Signaling Pathway in Human Pulmonary Mucoepidermoid NCI-H292 Cells.

The current study aimed to reveal the potential effect of meclofenamate, a nonsteroidal anti-inflammatory drug, on the gene expression of airway MUC5AC mucin. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with meclofenamate for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. Thereafter, the effect of meclofenamate on the PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was assessed. Meclofenamate inhibited glycoprotein production and mRNA expression of MUC5AC mucins induced by PMA by inhibiting the degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest meclofenamate suppresses mucin gene expression by regulating NF-kB signaling pathway in human pulmonary epithelial cells.

Negative emotion can be "more negative" for those with high metacognitive abilities when problem-solving.

Introduction: Metacognitive monitoring ability enables you to learn and solve problems more efficiently through appropriate strategies. At the same time, those who are high in monitoring ability are known to allocate more cognitive resources to the perception and control of negative emotions, as compared to those with low metacognitive ability. Therefore, while monitoring emotions may help reduce the negative emotion by enabling efficient control, it could also interrupt the use of an efficient strategy when problem-solving, as cognitive resources may be depleted. Methods: To confirm this, we divided participants into groups with high and low monitoring abilities and manipulated emotions by presenting emotional videos. Subsequent to the manipulation, problem solving strategies were examined using items from the Cognitive Reflection Test (CRT). Results: Results showed that those who were high in monitoring ability were shown to use more efficient problem-solving strategies than those who were lower in monitoring ability, but only in situations when positive or no emotions were manipulated. However, as hypothesized, when negative emotion was aroused, the CRT scores of high monitoring ability group were significantly lowered, decreasing to the same performance as those with low monitoring ability. We also found that metacognitive monitoring ability, when interacting with emotion, indirectly affected CRT scores, and that monitoring and control, when affected by emotion, were mediated in the process. Discussion: These findings suggest a novel and complicated interaction between emotion and metacognition and warrant further research.

Operative versus conservative treatment of trigger thumb in children.

Trigger thumb is an uncommon anomaly in children with controversial management ranging from simple observation to surgical release. This study aimed to determine the clinical outcomes of surgical release versus conservative treatment. Data from 407 children with 511 trigger thumbs were collected from their medical records. To compare the final outcomes of conservative and operative treatments, age at onset, sex, affected side, familial history, treatment modality, time to conversion from conservative to surgical treatment, recurrence, and complications were analyzed. Forty-one children were excluded owing to loss during follow-up; thus, 366 children were finally included. Conservative treatment was administered to 96 children, of whom 25 experienced successful result and 68 experienced treatment failure and were subsequently treated surgically. There were no cases of post-operative recurrence. After 24 months of age, operative treatment had better outcomes than conservative treatment, which showed a higher failure rate.

Betulin, an Anti-Inflammatory Triterpenoid Compound, Regulates MUC5AC Mucin Gene Expression through NF-kB Signaling in Human Airway Epithelial Cells.

Betulin is a triterpenoid natural product contained in several medicinal plants including Betulae Cortex. These medicinal plants have been used for controlling diverse inflammatory diseases in folk medicine and betulin showed anti-inflammatory, antioxidative, and anticancer activities. In this study, we tried to examine whether betulin exerts a regulative effect on the gene expression of MUC5AC mucin under the status simulating a pulmonary inflammation, in human airway epithelial cells. Confluent NCI-H292 cells were pretreated with betulin for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h or the indicated periods. The MUC5AC mucin mRNA expression and mucin glycoprotein production were measured by reverse transcription - polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. To elucidate the action mechanism of betulin, effect of betulin on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated by western blot analysis. The results were as follows: 1) Betulin significantly suppressed the production of MUC5AC mucin glycoprotein and down-regulated MUC5AC mRNA expression induced by PMA in NCI-H292 cells. 2) Betulin inhibited NF-κB activation stimulated by PMA. Suppression of inhibitory kappa B kinase (IKK) by betulin led to the inhibition of the phosphorylation and degradation of inhibitory kappa B alpha (IκBα), and the nuclear translocation of NF-κB p65. This, in turn, led to the down-regulation of MUC5AC glycoprotein production in NCI-H292 cells. These results suggest betulin inhibits the gene expression of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

Evaluation of Non-Fermented and Fermented Chinese Chive Juice as an Alternative to Antibiotic Growth Promoters of Broilers.

The present study explores the application of CC juice as a suitable feed additive and alternative to conventional antibiotics. We performed a comparative study to investigate the effects of non-fermented and fermented CC juice on broiler productivity, meat quality, blood characteristics, intestinal characteristics, and microbiota associated with intestinal characteristics. A total of 800 one-day-old Ross 308 broiler chickens were randomly assigned to one of the four dietary treatment groups: (1) basal diet (negative control; NC); (2) basal diet + 0.01% enramycin (positive control; PC); (3) basal diet + 3% non-fermented CC juice (NCC; CC juice 10%, water 90%); and (4) basal diet + 3% fermented CC juice (FCC; CC juice 10%, water 90%, Lactobacillus plantarum SK4719). Feed and water were provided ad libitum. Intriguingly, all treatments showed similar results in terms of broiler productivity and chicken meat quality. Considering organ characteristics, the FCC group showed a low spleen weight and lower (p < 0.05) blood levels of AST and total cholesterol (TCHO). Regarding intestinal characteristics, the CC feed additive (NCC and FCC) resulted in a heavier intestinal weight (p < 0.05) without affecting the length ratio of the villi or the crypt compared to the control (NC or PC). NCC and FCC lowered the growth of intestinal pathogens (p < 0.01). In summary, the addition of FCC can maintain poultry health by improving blood compositions and inhibiting the growth of intestinal pathogens, leading to a productivity comparable to that of poultry treated with growth-promoting antibiotics.

On-chip selection of adenosine aptamer using graphene oxide-coated magnetic nanoparticles.

Systematic evolution of ligands by exponential enrichment (SELEX) is a method that is generally used for developing aptamers, which have arisen the promising alternatives for antibodies. However, conventional SELEX methods have limitations, such as a limited selection of target molecules, time-consuming and complex fabrication processes, and labor-intensive processes, which result in low selection yields. Here, we used (i) graphene oxide (GO)-coated magnetic nanoparticles in the selection process for separation and label-free detection and (ii) a multilayered microfluidic device manufactured using a three-dimensionally printed mold that is equipped with automated control valves to achieve precise fluid flows. The developed on-chip aptamer selection device and GO-coated magnetic nanoparticles were used to screen aptamer candidates for adenosine in eight cycles of the selection process within approximately 2 h for each cycle. Based on results from isothermal titration calorimetry, an aptamer with a dissociation constant of 18.6 ± 1.5 µM was selected. Therefore, the on-chip platform based on GO-coated magnetic nanoparticles provides a novel label-free screening technology for biosensors and micro/nanobiotechnology for achieving high-quality aptamers.

Involvement of IKK/IkBα/NF-kB p65 Signaling into the Regulative Effect of Engeletin on MUC5AC Mucin Gene Expression in Human Airway Epithelial Cells.

In this study, we examined whether engeletin exerts an effect on the gene expression of MUC5AC mucin, in human pulmonary epithelial NCI-H292 cells. The cells were pretreated with engeletin for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of engeletin on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated. Engeletin suppressed the mRNA expression and production of MUC5AC mucin, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest engeletin inhibits the gene expression of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

Potential Probiotic Acceptability of a Novel Strain of Paenibacillus konkukensis SK 3146 and Its Dietary Effects on Growth Performance, Intestinal Microbiota, and Meat Quality in Broilers.

This study evaluates the in vitro probiotic characteristics of P. konkukensis sp. nov. SK-3146, which was isolated from animal feed, and its dietary effects on growth performance, intestinal characteristics, intestinal microbiota, and meat quality in broilers. In vitro experiments revealed that P. konkukensis was non-hemolytic with variable antibiotic susceptibility, and acid as well as bile tolerance. To assess the effect of P. konkukensis on broilers, a total of four hundred eighty 1-day-old Ross 308 broiler chicks were allocated to 3 treatment groups with 4 replicates of 40 birds each; the negative control group was fed a basal diet without any feed additives (NC), the positive control group was fed a basal diet containing 0.01% enramycin (PC), and the experimental group was fed a basal diet containing P. konkukensis bacterial culture (PK) at 104 CFU/g of the diet based on bacterial count. The experiment lasted for 35 days. Results indicated that there were no significant differences in any growth performance parameters among the dietary treatments (p > 0.05). In addition, the inclusion of P. konkukensis in the broilers' diet did not affect meat cooking loss, color, and pH but increased the relative weight of breast meat (p < 0.05). The PK group showed heavier intestinal weight and shorter intestinal length than the NC group (p < 0.05). The ratio of the intestinal weight to length of jejunum was the highest in the PK group (p < 0.05). The PK group showed increased counts of Streptococcus thermophilus (p < 0.05) with no adverse effects of P. konkukensis on other intestinal microbiota in the jejunum. This study implies that P. konkukensis might have the potential to be applied as a probiotic feed additive in poultry.

Inhibitory Effect of Mitoxantrone on Collagen Synthesis in Dermal Fibroblasts.

Background: Fibroblasts produce collagen molecules that support the structure of the skin. The decrease and hypersynthesis of collagen causes skin problems such as skin atrophy, wrinkles and scars. Objective: The purpose of this study is to investigate the mechanism of mitoxantrone on collagen synthesis in fibroblasts. Methods: Cultured fibroblasts were treated with mitoxantrone, and then collagen synthesis was confirmed by reverse transcription-polymerase chain reaction and Western blot. Results: Mitoxantrone inhibited the expression of type I collagen in fibroblasts at both the mRNA and protein levels. In the collagen gel contraction assay, mitoxantrone significantly inhibited gel contraction compared to the control group. Mitoxantrone inhibited transforming growth factor (TGF)-ß-induced phosphorylation of SMAD3. Finally, mitoxantrone inhibited the expression of LARP6, an RNA-binding protein that regulates collagen mRNA stability. Conclusion: These results suggest that mitoxantrone reduces collagen synthesis by inhibiting TGF-ß/SMAD signaling and LARP6 expression in fibroblasts, which can be developed as a therapeutic agent for diseases caused by collagen hypersynthesis.

Sorafenib induces pigmentation via the regulation of ß-catenin signalling pathway in melanoma cells.

We conducted large-scale screening test on drugs that were already approved for other diseases to find pigmentation-modulating agents. Among drugs with potential for pigmentation control, we selected sorafenib and further investigated the effect on pigmentation using HM3KO melanoma cells. As a result of treating melanoma cells with sorafenib, pigmentation was promoted in terms of melanin content and tyrosinase activity. Sorafenib increased mRNA and protein levels of pigmentation-related genes such as MITF, tyrosinase and TRP1. To uncover the action mechanism, we investigated the effect of sorafenib on the intracellular signalling pathways. Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. In addition, sorafenib significantly increased the level of active ß-catenin, together with activation of ß-catenin signalling. Mechanistic study revealed that sorafenib decreased phosphorylation of serine 9 (S9) of GSK3ß, while it increased phosphorylation of tyrosine 216 (Y216) of GSK3ß. These results suggest that sorafenib activates the ß-catenin signalling through the regulation of GSK3ß phosphorylation, thereby affecting the pigmentation process.

Secondary synovial chondromatosis of the subacromial subdeltoid bursa with coexisting glenohumeral osteoarthritis: Case report.

RATIONALE: Synovial chondromatosis of the shoulder joint is uncommon; this condition usually affects the knee joint and the hip joint. Lesions of multiple chondral nodules form in the synovium and are usually found within the joint capsule. Treatment of synovial chondromatosis consists of loose body removal and synovectomy. In synovial chondromatosis of the shoulder, arthroscopic loose body removal and synovectomy have been reported with good outcomes. Arthroplasty can be a treatment option when osteoarthritis co-occurs at the affected joint. Since incidence of glenohumeral joint osteoarthritis is low compared to osteoarthritis of the knee or hip joints, reports of shoulder synovial chondromatosis treated with arthroplasty are scarce. PATIENT CONCERNS: A 79-year-old woman presented with right shoulder pain with loss of motion for several years without a history of trauma. DIAGNOSES: Degenerative changes in the humeral head and glenoid were noted and multiple loose bodies were found in the subdeltoid bursa, and the subacromial bursa. The pathology of loose bodies showed degenerated cartilage tissue and some bony components. Characteristic concentric rings of calcification were observed, indicative of secondary synovial chondromatosis. The diagnosis was secondary synovial chondromatosis of the subacromial subdeltoid bursa with coexisting glenohumeral osteoarthritis. INTERVENTIONS: The patient was treated with loose body removal, extensive synovectomy, bursectomy and reverse total shoulder arthroplasty. OUTCOMES: Visual analog scale for shoulder pain, range of motion of shoulder joint had improved demonstrating a good short-term outcome and there was no radiographic evidence of disease recurrence. LESSONS: In synovial chondromatosis of the shoulder, loose bodies may form in the bursa. In combination with degenerative osteoarthritis of the glenohumeral joint, arthroplasty is a viable option.

Feasibility of sodium long chain polyphosphate as a potential growth promoter in broilers.

The objective of this study was to evaluate in vitro antimicrobial and anti-biofilm activity of sodium long chain polyphosphate (SLCPP) and effect of dietary supplementation of SLCPP on growth performance, organ characteristics, blood metabolites, and intestinal microflora of broilers. Antimicrobial activities of SLCPP were observed against Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica ser. Pullorum, Shigella sonnei, Klebsiella pneumonia, Pseudomonas aeruginosa in agar well diffusion assay. In addition, SLCPP demonstrated good anti-biofilm activity against K. pneumonia and P. aeruginosa. Furthermore, to investigate the dietary effect of SLCPP, a total of 480 1-day-old male Ross 308 broiler chicks were randomly allotted to three dietary treatment groups (4 replicates per group, 40 birds in each replicate): an antibiotic-free corn-soybean meal basal diet (NC); basal diet + enramycin 0.01% (PC); and basal diet + 0.1% SLCPP (SPP). The experiment lasted for 35 days. Results showed that birds fed with SLCPP had higher body weight (BW) and average daily gain (ADG), and lower feed conversion ratio (FCR) during the grower phase (days 7 to 21) (p < 0.05). Except for blood urea nitrogen, all other blood biochemical parameters remained unaffected by the dietary supplementation of SLCPP. Compared to the control group, lengths of the duodenum and ileum in the SPP group were significantly shorter (p < 0.05). Moreover, counts of lactic acid bacteria (LAB), total aerobes, and Streptococcus spp. in jejunum as well as LAB in cecum were increased in the SPP group than in the PC group (p < 0.05). These results suggest that dietary supplementation of SLCPP might promote the growth of broilers in their early growth phase.

Prediction of biogas production rate from dry anaerobic digestion of food waste: Process-based approach vs. recurrent neural network black-box model.

The stability of dry anaerobic digestion (AD) of food waste (FW) as well as the resulting methane gas generation was investigated from the perspective of system dynamics. Various organic loading rates were applied to the system by modifying the water content in the FW feed and solid retention time (SRT). The excessive organic loading due to the accumulation of volatile fatty acids (VFAs) from the feed with 80% water content during the short SRT (15 and 20 d) caused system failure. In contrast, more intermediate materials, such as VFAs, was easily converted into methane at higher water contents. In addition, the biogas production rate of dry AD was effectively predicted based on SRT, soluble chemical oxygen demand, total VFA, total ammonia, and free ammonia using a recurrent neural network-the so-called "black-box" model. This implies the feasibility of applying this data-based black-box model for controlling and optimizing complex biological processes.

Species Differences in Stereoselective Pharmacokinetics of HSG4112, A New Anti-Obesity Agent.

HSG4112, a racemic drug, is a new anti-obesity agent. In this study, the stereoselective pharmacokinetics of HSG4112 were investigated in rats and dogs, and the underlying mechanism was investigated. The plasma concentrations of HSG4112(S) and HSG4112(R) were quantitated in plasma from rats and beagle dogs after IV and/or oral administration of racemic HSG4112. The concentration of HSG4112(S) was significantly higher than that of HSG4112(R) in rat plasma. Contrarily, the concentration of HSG4112(R) was significantly higher than HSG4112(S) in dog plasma. A metabolic stability test with liver microsomes showed that HSG4112(S) was more stable than HSG4112(R) in rat liver microsomes, but the difference between stereoisomers did not appear in dog liver microsomes. However, the stereoselectivity was observed in dog liver and intestinal microsomes after uridine 5'-diphospho-glucuronic acid was added. Thus, stereoselective metabolism by uridine 5'-diphospho-glucuronosyltransferases is mainly responsible for the stereoselective pharmacokinetics in dogs. These results suggest that the species difference in the stereoselective plasma pharmacokinetics of HSG4112 is due to the stereoselective metabolism.