Structural Optimization of a Knuckle with Consideration of Stiffness and Durability Requirements

The automobile’s knuckle is connected to the parts of the steering system and the suspension system and it is used for adjusting the direction of a rotation through its attachment to the wheel. This study changes the existing material made of GCD45 to Al6082M and recommends the lightweight design of the knuckle as the optimal design technique to be installed in small cars. Six shape design variables were selected for the optimization of the knuckle and the criteria relevant to stiffness and durability were considered as the design requirements during the optimization process. The metamodel-based optimization method that uses the kriging interpolation method as the optimization technique was applied. The result shows that all constraints for stiffness and durability are satisfied using A16082M, while reducing the weight of the knuckle by 60% compared to that of the existing GCD450

The Characteristics of Action Potentials in Primo Vessels and the Effects of Acetylcholine Injection to the Action Potentials

In a previous study, we found that Primo vessels generate different action potentials in smooth muscles, but this study compared the pulse shape to distinguish the two tissues. Thus, a more sophisticated extracellular experiment was performed in this study using an acetylcholine injection; we then observed changes in the amplitude, FWHM (full width at half maximum), and period to explore Primo vessel function. A third type of pulse was recorded for Primo vessels. We observed fast depolarizing and repolarizing phases for this pulse. Further, its FWHM was 30 ms between smooth muscles and neurons. Acetylcholine affected only the period. The amplitude and FWHM were consistent after injection. Primo-vessels generated action potentials at twice the frequency after injection. From the results, we speculate that Primo-vessels perform a role in transferring signals in a different manner, which may be relevant for acupuncture treatment

Tool Development for Cancer Patients' Sexuality Information Needs

PURPOSE: This study aimed to develop a scale measuring sexuality information needs of patients with cancer. METHODS: Nine items of sexuality information needs were based on the PLISSIT model and concepts of sexual rights. A factor analysis using principal axis factoring and Cronbach's alpha were performed to test validity and reliability. Data were collected from 211 patients with cancer visiting a cancer center in Seoul, Korea. RESULTS: Factor loadings of the 9 items of sub scales ranged from .43 to .96. Three factors in this study explained 74.4% of the total variance. Cronbach's alpha of the 9 items was .83. CONCLUSION: The scale of information needs about sexuality showed acceptable construct validity and reliability. This scale would be useful to assess the levels of information needs for sexuality for patients with cancer. The possibility of the scales' expansion to other group could be investigated in future studies

Mesenchymal stem cells genetically engineered to express platelet-derived growth factor and heme oxygenase-1 ameliorate osteoarthritis in a canine model

Background Mesenchymal stem cells (MSCs) are used for the treatment of osteoarthritis (OA), and MSC genetic engineering is expected to enhance cartilage repair. Here, we aimed to investigate the effect of MSCs overexpressing platelet-derived growth factor (PDGF) or heme oxygenase-1 (HO-1) in chondrocytes and synovial cells with an OA phenotype and assess the in vivo efficacy of intra-articular injections of these MSCs in canine OA models. Methods Canine adipose-derived MSCs were transfected with canine PDGF (PDGF-MSCs) or HO-1 (HO-1-MSCs) using lentiviral vectors. Canine chondrocytes or synovial cells were stimulated with lipopolysaccharide (LPS) to mimic the inflammatory OA model and then co-cultured with MSCs, PDGF-MSCs, or HO-1-MSCs for 24 h and 72 h. The mRNA levels of pro-inflammatory, extracellular matrix-degradative/synthetic, or pain-related factors were measured after co-culture by real-time PCR. Furthermore, a surgery-induced canine OA model was established and the dogs were randomized into four groups: normal saline (n = 4), MSCs (n = 4), PDGF-MSCs (n = 4), and HO-1-MSCs (n = 4). The OA symptoms, radiographic OA severity, and serum matrix metallopeptidase (MMP)-13 levels were assessed before and 10 weeks after treatment, to evaluate the safety and efficacy of the modified MSCs. Results PDGF or HO-1 overexpression significantly reduced the expression of pro-inflammatory factors, MMP-13, and nerve growth factor elicited by LPS and increased that of aggrecan and collagen type 2 in chondrocytes (P < 0.05). In addition, the expression of aggrecanases was significantly downregulated in synovial cells, whereas that of tissue inhibitor of metalloproteinases was upregulated (P < 0.05). Furthermore, the co-cultured MSCs highly expressed genes that contributed to the maintenance of joint homeostasis (P < 0.05). In vivo studies showed that OA symptoms improved after administration of all MSCs. Also, PDGF-MSCs significantly improved limb function and reduced pain (P < 0.05). The results of the radiographic assessment and serum MMP-13 levels did not vary significantly compared to those of the control. Conclusions Genetically modifying PDGF and HO-1 in MSCs is an effective strategy for treating OA, suggesting that PDGF-MSCs can be novel therapeutic agents for improving OA symptoms

Suggested Indications for Enucleation of Solid Pseudopapillary Neoplasms in Pediatric Patients

Background: Solid pseudopapillary neoplasms (SPNs) are rare, low-grade, malignant neoplasms that can occur in pediatric patients. Although complete resection of the tumor is the principle treatment, SPN enucleation (EN) has been reported to be effective in children. This study aimed to examine the feasibility and safety of EN by comparing it with conventional pancreatectomy (CP), and to present the indications for its use in pediatric patients.Methods: We retrospectively reviewed the medical records of 66 patients who underwent surgery for SPN at our institution from October 1992 to April 2018. Surgical methods, postoperative complications, hospital stay, and recurrence were compared.Results: Of the 66 patients, 15 (22.7%) were treated with EN and 51 (77.3%) were treated with CP. The mean duration of EN operation was 262 min (±145 min) and of CP was 345 min (±195 min). There was no statistically significant difference between the two methods (P = 0.13). To objectively compare the mass size between patients, we introduced a tumor size/intraperitoneal width ratio, which also revealed no significant difference between the 2 surgery groups (P = 0.21). The EN group had one case of recurrence at the resection site. The complications observed were fluid collection, splenic infarctions, hematomas, pancreatic fistulas, portal vein thromboses, and chylous drainage, among which pancreatic fistulas were the most frequent followed by moderate-severe fistulas in the EN group (P &lt; 0.001). The mean postoperative fasting time (EN 17.0 ± 8.7 days vs. CP 5.1 ± 3.3 days, P &lt; 0.001) and mean hospital stay (EN 23.4 ± 10.0 days vs. CP 13.2 ± 6.5 days, P = 0.002) showed statistically significant differences.Conclusion: Compared with CP treatment, EN of SPNs in children has the disadvantages of prolonged fasting times and hospital stays to recover from moderate pancreatic fistulas. However, if appropriate indications are applied, EN can be considered a safe and effective surgical procedure for children

Comparison of the antibody responses to Plasmodium vivax and Plasmodium falciparum antigens in residents of Mandalay, Myanmar

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the profile of antibodies against several antigens of <it>Plasmodium vivax </it>and <it>Plasmodium falciparum </it>in Mandalay, Myanmar.</p> <p>Methods</p> <p>Malaria parasites were identified by microscopic examination. To test the antibodies against <it>P. vivax </it>and <it>P. falciparum </it>in sera, an indirect immunofluorescence antibody test (IFAT) was performed using asexual blood parasite antigens. An enzyme-linked immunosorbent assay (ELISA) was performed with circumsporozoite protein (CSP), Pvs25 and Pvs28 recombinant proteins of transmission-blocking vaccine candidates for <it>P. vivax</it>, and liver stage specific antigen-1 and -3 (PfLSA-1, PfLSA-3) for <it>P. falciparum</it>.</p> <p>Results</p> <p>Fourteen patients among 112 were found to be infected with <it>P. vivax </it>and 26 with <it>P. falciparum </it>by thick smear examination. Twenty-three patients were found to be infected with <it>P. vivax</it>, 19 with <it>P. falciparum </it>and five with both by thin smear examination. Blood samples were divided into two groups: Group I consisted of patients who were positive for infection by microscopic examination, and Group II consisted of those who showed symptoms, but were negative in microscopic examination. In <it>P. falciparum</it>, IgG against the blood stage antigen in Group I (80.8%) was higher than in Group II (70.0%). In <it>P. vivax</it>, IgG against the blood stage antigen in Group I (53.8%) was higher than in Group II (41.7%). However, the positivity rate of the PvCSP VK210 subtype in Group II (40.0%) was higher than in Group I (23.1%). Similarly for the PvCSP VK247 subtype, Group II (21.7%) was higher than that for Group I (9.6%). A similar pattern was observed in the ELISA using Pvs25 and Pvs28: positive rates of Group II were higher than those for Group I. However, those differences were not shown significant in statistics.</p> <p>Conclusions</p> <p>The positive rates for blood stage antigens of <it>P. falciparum </it>were higher in Group I than in Group II, but the positive rates for antigens of other stages (PfLSA-1 and -3) showed opposite results. Similar to <it>P. falciparum</it>, the positive rate of pre-blood stage (CSP VK210 and 247 subtype) and post-blood stage (Pvs25 and 28) antigens of <it>P. vivax </it>were higher in Group II than in Group I. Therefore, sero-diagnosis is not helpful to discriminate between malaria patients and symptomatic individuals during the epidemic season in Myanmar.</p

Evaluation of the transporter-mediated herb-drug interaction potential of DA-9801, a standardized dioscorea extract for diabetic neuropathy, in human in vitro and rat in vivo

BACKGROUND: Drug transporters play important roles in the absorption, distribution, and elimination of drugs and thereby, modulate drug efficacy and toxicity. With a growing use of poly pharmacy, concurrent administration of herbal extracts that modulate transporter activities with drugs can cause serious adverse reactions. Therefore, prediction and evaluation of drug-drug interaction potential is important in the clinic and in the drug development process. DA-9801, comprising a mixed extract of Dioscoreae rhizoma and Dioscorea nipponica Makino, is a new standardized extract currently being evaluated for diabetic peripheral neuropathy in a phase II clinical study. METHOD: The inhibitory effects of DA-9801 on the transport functions of organic cation transporter (OCT)1, OCT2, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) were investigated in HEK293 or LLC-PK1 cells. The effects of DA-9801 on the pharmacokinetics of relevant substrate drugs of these transporters were also examined in vivo in rats. RESULTS: DA-9801 inhibited the in vitro transport activities of OCT1, OCT2, OAT3, and OATP1B1, with IC(50) values of 106, 174, 48.1, and 273 μg/mL, respectively, while the other transporters were not inhibited by 300 μg/mL DA-9801. To investigate whether this inhibitory effect of DA-9801 on OCT1, OCT2, and OAT3 could change the pharmacokinetics of their substrates in vivo, we measured the pharmacokinetics of cimetidine, a substrate for OCT1, OCT2, and OAT3, and of furosemide, a substrate for OAT1 and OAT3, by co-administration of DA-9801 at a single oral dose of 1,000 mg/kg. Pre-dose of DA-9801 5 min or 2 h prior to cimetidine administration decreased the C(max) of cimetidine in rats. However, DA-9801 did not affect the elimination parameters such as half-life, clearance, or amount excreted in the urine, suggesting that it did not inhibit elimination process of cimetidine, which is governed by OCT1, OCT2, and OAT3. Moreover, DA-9801 did not affect the pharmacokinetic characteristics of furosemide, as evidenced by its unchanged pharmacokinetic parameters. CONCLUSION: Inhibitory effects of DA-9801 on OCT1, OCT2, and OAT3 observed in vitro may not necessarily translate into in vivo herb-drug interactions in rats even at its maximum effective dose