Evaluation of Vancomycin TDM Strategies: Prediction and Prevention of Kidney Injuries Based on Vancomycin TDM Results.

The current guidelines for therapeutic drug monitoring (TDM) of vancomycin suggest a target 24-hour area under the curve (AUC0-24) of 400 to 600 mg*h/L for serious methicillin-resistant Staphylococcus aureus infections. In this study, the predictabilities of acute kidney injury (AKI) of various TDM target parameters, target levels, and sampling methods were evaluated in patients who underwent TDM from January 2020 to December 2020. The AUC0-24 and trough values were calculated by both one- and two-point sampling methods, and were evaluated for the predictability of AKI. Among the AUC0-24 cutoff comparisons, the threshold value of 500 mg*h/L in the two sampling methods was statistically significant (P = 0.042) when evaluated for the predictability of AKI. Analysis by an receiver operating characteristic curve estimated an AUC0-24 cutoff value of 563.45 mg*h/L as a predictor of AKI, and was proposed as the upper limit of TDM target.

Peroxisome Proliferator Activated Receptor-γ Agonistic Compounds from the Jellyfish-Derived Fungus Cladosporium oxysporum.

In our search for peroxisome proliferator-activated receptor (PPAR) agonists, five undescribed compounds, namely two acyclic diterpenes (1 and 2; cladopsol A and cladopsol B), two sesquiterpenes (3 and 4; cladopsol C and cladopsol D), and one C21-ecdysteroid (5; cladopsol E), and 15 known compounds were isolated from the jellyfish-derived fungus - Cladosporium oxysporum. The structures of the undescribed compounds were defined using UV, NMR, HR-ESI-MS, and electronic circular dichroism (ECD) spectroscopy and a modified Mosher's method. Luciferase reporter assay and docking analysis suggested that cladopsol B may function as a PPAR-γ partial agonist with a potential antidiabetic lead which may evade the side effects of full agonists. Moreover, cladopsol B stimulated glucose uptake in HepG2 cells with an efficacy comparable to that of rosiglitazone, but with less side effect induced by lipid accumulation in 3T3-L1 cells. Therefore, cladopsol B could serve as a molecular skeleton in a study of advanced antidiabetic lead with less side effect.

Fraxinol Stimulates Melanogenesis in B16F10 Mouse Melanoma Cells through CREB/MITF Signaling.

Melanin pigment produced in melanocytes plays a protective role against ultraviolet radiation. Selective destruction of melanocytes causes chronic depigmentation conditions such as vitiligo, for which there are very few specific medical treatments. Here, we found that fraxinol, a natural coumarin from Fraxinus plants, effectively stimulated melanogenesis. Treatment of B16-F10 cells with fraxinol increased the melanin content and tyrosinase activity in a concentration-dependent manner without causing cytotoxicity. Additionally, fraxinol enhanced the mRNA expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. Fraxinol also increased the expression of microphthalmia-associated transcription factor at both mRNA and protein levels. Fraxinol upregulated the phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB). Furthermore, H89, a cAMP-dependent protein kinase A inhibitor, decreased fraxinol-induced CREB phosphorylation and microphthalmia-associated transcription factor expression and significantly attenuated the fraxinol-induced melanin content and intracellular tyrosinase activity. These results suggest that fraxinol enhances melanogenesis via a protein kinase A-mediated mechanism, which may be useful for developing potent melanogenesis stimulators.

Quorum sensing-dependent post-secretional activation of extracellular proteases in Pseudomonas aeruginosa.

Pseudomonas aeruginosa secretes multiple proteases that are implicated in its pathogenesis, and most of them are regulated by quorum sensing (QS). In this study, we found that the activities of three major extracellular proteases, protease IV (PIV), elastase A (LasA), and elastase B (LasB), are reduced considerably when expressed in a QS mutant (MW1). PIV and LasA expressed in MW1 exhibited little activity, even when purified, and their activities were inhibited by noncleavage or binding of their propeptides. LasB was activated by a QS-dependent factor, indicating that, unlike what has been proposed previously, LasB is not autoactivated. When LasB was relieved from inhibition, it activated PIV, which then sequentially processed pro-LasA to mature LasA. When activated, LasB was not inhibited by exogenous addition of its propeptide, but LasA and PIV were inhibited by their propeptides, even after prior activation. These differences may be explained by the fact that LasB can degrade its own propeptide but PIV and LasA cannot. We also found that, although PIV is the preferred LasA-activating factor, LasB can also partially activate LasA. Overall, LasB, PIV, and LasA were activated postsecretionally in a cascading manner in which the initial activation of LasB was controlled tightly by QS at the protein level in addition to the well-known transcriptional control of these proteases by QS. Interestingly, human elastase also activated LasA, indicating that the activation cascade is triggered by host factors during infection. In summary, a QS-induced proteolytic cascade activates secreted proteases from P. aeruginosa.

Thermoregulation of Pseudomonas aeruginosa Biofilm Formation.

We investigated the effect of temperature on the biofilm formation of Pseudomonas aeruginosa and revealed that the biofilm formation increased rapidly at temperatures lower than 25°C. P. aeruginosa formed the most robust biofilm of a conspicuous mushroom-like structure at 20°C. However, when the temperature increased to 25°C, the biofilm formation rapidly decreased. Above 25°C, as the temperature rose, the biofilm formation increased again little by little despite its less-structured form, indicating that 25°C is the low point of biofilm formation. The intracellular 3',5'-cyclic diguanylate (c-di-GMP) levels also decreased rapidly as the temperature rose from 20 to 25°C. The expression levels of pelA, algD, and pslA encoding Pel, alginate, and Psl, respectively, were also dramatically affected by temperature, with pelA being regulated in a pattern similar to that of the intracellular c-di-GMP levels, and the pattern seen for algD regulation was the most similar to the actual biofilm formation pattern. Total exopolysaccharide production was thermoregulated and followed the regulation pattern of c-di-GMP. Interestingly, the thermoregulation patterns in biofilm formation were different depending on the strain of P. aeruginosa Unlike PAO1, another strain, PA14, showed a gradual decrease in biofilm formation and c-di-GMP in the range of 20 to 37°C, and P. aeruginosa clinical isolates also showed slightly different patterns in biofilm formation in conjunction with temperature change, suggesting that different strains may sense different temperature ranges for biofilm formation. However, it is obvious that P. aeruginosa forms more biofilms at lower temperatures and that temperature is an important factor in determining the biofilm formation.IMPORTANCE Biofilm formation is an important protection mechanism used by most microorganisms and provides cells with many advantages, like high infectivity, antibiotic resistance, and strong survivability. Since most persistent bacterial infections are believed to be associated with biofilms, biofilm control is an important issue in medicine, environmental engineering, and industry. Biofilm formation is influenced by various environmental factors. Temperature is the most direct environmental cue encountered by microorganisms. Here, we investigated the effect of temperature on the biofilm formation of P. aeruginosa, a notorious pathogen, and found that temperature is an important factor determining the amount and structure of biofilms. Low temperatures greatly increase biofilm formation and give biofilms a highly conspicuous structure. Although thermoregulation of biofilm formation is mainly mediated by c-di-GMP, some c-di-GMP-independent regulations were also observed. This study shows how biofilms are formed at various temperatures and provides new insights to control biofilms using temperature.

Predicting the Depth of the Lumbar Plexus in Pediatric Patients: A Retrospective Magnetic Resonance Imaging Study.

BACKGROUND: The lumbar plexus (LP) block is commonly used for analgesia for lower extremities. If the depth of the LP (LPD) can be predicted, the performance time and procedure-related complications could be reduced. METHODS: Three hundred sixty-one magnetic resonance images of pediatric patients (<18 years of age) were analyzed. Simple linear regression and multiple linear regression analyses were performed to predict the LPD using patient age, weight, height, and the distance between the midline and posterior superior iliac spine (midline-PSIS). The ratio of the distance between the midline and the most lateral aspect of the LP (midline-LP) to midline-PSIS (midline-LP/midline-PSIS ratio) was calculated to suggest a needle insertion point at the L4/L5 intervertebral level. The presence of the kidney at the L4 level and the L4/L5 intervertebral level was determined. RESULTS: The LPD at the L4/L5 intervertebral levels was predicted using the equation LPD = 0.844 × weight (kg) + 25.8 (mm) in pediatric patients <18 years of age (r = 0.791; 95% confidence interval [CI] of r, 0.753-0.829). The overall midline-LP/midline-PSIS ratio was 0.87 (95% CI, 0.86-0.89), and the ratio was higher in neonates and infants (0.98 [95% CI, 0.95-1.02]) than in the other age groups. The presence of the lower kidney pole at the L4 level was common in pediatric patients (43.7% of neonates and infants and 13.7% of toddlers and preschool-aged children). The lower kidney pole was observed at the L4/L5 level in 6 patients (1.7%). CONCLUSIONS: When LP block is performed in pediatric patients, the LPD and risk of renal injury should be considered for successful and safe analgesic block.

Analytical performance evaluation of the Norudia HbA1c assay.

BACKGROUND: Hemoglobin A1c (HbA1c) is arguably the most important biomarker used in the diagnosis and treatment monitoring of diabetes mellitus. We evaluated the analytical performance of the Norudia HbA1c assay (Sekisui Medical Co., LTD), which uses an enzymatic method incorporated into a fully automated, high-throughput system. METHODS: The precision, linearity, and carryover of the Norudia HbA1c assay were evaluated. Using 60 patient samples, comparative analysis of HbA1c measurements with two commonly used HbA1c assays, the D100 (Bio-Rad Laboratories, Inc) and HLC-723 G11 (Tosoh), was undergone. Thirteen commutable samples with known HbA1c concentrations measured using an IFCC reference measurement procedure were used to compare accuracy between methods. Interference of HbA1c measurement by Hb variants was evaluated using 16 known Hb variant samples. RESULTS: Repeatability (% CV) for low and high concentrations ranged from 1.12%-1.50% and 0.66%-0.75%, respectively, and within-laboratory precision for low and high concentrations ranged from 1.73%-2.89% and 0.98%-1.64%, respectively. For linearity, the coefficient of determination was 0.9987. No significant carryover was observed. When compared to the D100 and HLC-723 G11 assays, the Norudia HbA1c assay showed the best accuracy with the lowest mean bias (-1.72%). Furthermore, the Norudia was least affected by Hb variants and gave the most reliable HbA1c measurements. CONCLUSION: The Norudia HbA1c showed excellent analytical performance with good precision and linearity, and minimal carryover. When compared to other routine HbA1c methods, the Norudia HbA1c assay showed the highest accuracy and was least affected by Hb variants.

C5, A Cassaine Diterpenoid Amine, Induces Apoptosis via the Extrinsic Pathways in Human Lung Cancer Cells and Human Lymphoma Cells.

Apoptosis pathways in cells are classified into two pathways: the extrinsic pathway, mediated by binding of the ligand to a death receptor and the intrinsic pathway, mediated by mitochondria. Apoptosis is regulated by various proteins such as Bcl-2 (B-cell lymphoma 2) family and cellular FLICE (Fas-associated Death Domain Protein Interleukin-1ß-converting enzyme)-inhibitory protein (c-FLIP), which have been reported to inhibit caspase-8 activity. In this study, it was found that C5 (3ß-Acetyl-nor-erythrophlamide), a compound of cassaine diterpene amine from Erythrophleum fordii, induced cell apoptosis in a variety of types of cancer cells. Induction of apoptosis in cancer cells by C5 was inversely related to the level of Bcl-2 expression. Overexpression of Bcl-2 into cancer cells significantly decreased C5-induced apoptosis. It was also found that treatment of cancer cells with a caspase-8 inhibitor significantly suppressed C5-induced apoptosis; however, treatment with caspase-9 inhibitors did not affect C5-induced apoptosis, suggesting that C5 may induce apoptosis via the extrinsic pathway by activating caspase-8. It was confirmed that treatment with C5 alone induced an association of FADD with procaspase-8; however, overexpression of c-FLIP decreased C5-induced caspase-8 activation. In conclusion, C5 could be utilized as a new useful lead compound for the development of an anti-cancer agent that has the goal of apoptosis.

Initial Evidence on the Impact of Performance-Based Treadmill Training on Pulmonary Function and Physical Performance in a Child with Bronchopulmonary Dysplasia: Single-Subject Experimental Study.

Aim: This study aimed to demonstrate the initial evidence on the impact of performance-based treadmill training on pulmonary function and physical performance of a patient with bronchopulmonary dysplasia (BPD).Methods: This study used a single-subject pre-experimental (A-B) research design (5 and 10 data points during the baseline and intervention phases, respectively) with a 4-month follow-up measurement. The subjects were a 5-year-old child diagnosed with bronchopulmonary dysplasia. Outcome measures were pulmonary function (forced vital capacity [FVC] and peak expiratory flow [PEF]) and physical performance (6-min walk test [6MWT], sit-to-stand test [STS], pediatric balance scale [PBS], and goal attainment scaling).Results: Applying the 2 standard deviation method, the FVC, PEF, 6MWT, and STS test scores showed significant improvement compared to baseline values. In addition, the PBS and goal attainment scaling scores improved by 5.36% (42 points to 45 points) and 29.61% (37.6 points to 59.75 points) after the intervention, respectively. Gains were maintained at the 4-month follow-up.Conclusions: These findings suggest that performance-based treadmill training may be a possible treatment option to improve the pulmonary function and physical performance of children with BPD. Further rigorous studies are needed to establish evidence regarding the effectiveness of the training program among this population.

Lumbosacral and thoracolumbosacral cerebrospinal fluid volume changes in neonates, infants, children, and adolescents: A retrospective magnetic resonance imaging study.

BACKGROUND: The volume of cerebrospinal fluid can affect the pharmacokinetics and pharmacodynamics of local anesthetics for spinal anesthesia and other intrathecal medications. AIMS: The objective of this study was to estimate the lumbosacral cerebrospinal fluid volume and thoracolumbosacral cerebrospinal fluid volume using magnetic resonance images in pediatric patients from neonates and infants to adolescents. METHODS: Spinal magnetic resonance images of 500 pediatric patients (age <18 years) were reviewed. The lumbosacral cerebrospinal fluid volumes of 418 patients and thoracolumbosacral cerebrospinal fluid volumes of 248 patients were measured. The relationship between cerebrospinal fluid volumes and age, height, and weight were evaluated. The lumbosacral and thoracolumbosacral cerebrospinal fluid volumes per weight were calculated to elucidate developmental changes. RESULTS: The lumbosacral and thoracolumbosacral cerebrospinal fluid volumes showed linear correlations with height (r2  = 0.730 and r2  = 0.661, respectively), whereas they showed curvilinear correlations with age (r2  = 0.752 and r2  = 0.717, respectively) and weight (r2  = 0.734 and r2  = 0.734, respectively). The mean lumbosacral cerebrospinal fluid volume per weight (mL/kg) was 0.85 (standard deviation [SD]: 0.19, 95% confidence interval [CI]: 0.81-0.90) in neonates and infants, 0.86 (SD: 0.22, 95% CI: 0.83-0.89) in toddlers and preschoolers, 0.71 (SD: 0.26, 95% CI: 0.66-0.76) in schoolers, and 0.54 (SD: 0.20, 95% CI: 0.49-0.60) in adolescents. The mean thoracolumbosacral cerebrospinal fluid volume per weight (mL/kg) was 1.95 (SD: 0.37, 95% CI: 1.86-2.04) in neonates and infants, 1.82 (SD: 0.41, 95% CI: 1.75-1.88) in toddlers and preschoolers, 1.38 (SD: 0.40, 95% CI: 1.23-1.52) in schoolers, and 0.99 (SD: 0.34, 95% CI: 0.45-1.53) in adolescents. CONCLUSION: The lumbosacral and thoracolumbosacral cerebrospinal fluid volumes in pediatric patients were much smaller than previously presented values, showing linear correlations with height, and demonstrate curvilinear correlations with age and weight.

Bacterial ornithine lipid, a surrogate membrane lipid under phosphate-limiting conditions, plays important roles in bacterial persistence and interaction with host.

Ornithine lipids (OLs) are bacteria-specific lipids that are found in the outer membrane of Gram (-) bacteria and increase as surrogates of phospholipids under phosphate-limited environmental conditions. We investigated the effects of OL increase in bacterial membranes on pathogen virulence and the host immune response. In Pseudomonas aeruginosa, we increased OL levels in membranes by overexpressing the OL-synthesizing operon (olsBA). These increases changed the bacterial surface charge and hydrophobicity, which reduced bacterial susceptibility to antibiotics and antimicrobial peptides (AMPs), interfered with the binding of macrophages to bacterial cells and enhanced bacterial biofilm formation. When grown under low phosphate conditions, P. aeruginosa became more persistent in the treatment of antibiotics and AMPs in an olsBA-dependent manner. While OLs increased persistence, they attenuated P. aeruginosa virulence; in host cells, they reduced the production of inflammatory factors (iNOS, COX-2, PGE2 and nitric oxide) and increased intracellular Ca2+ release. Exogenously added OL had similar effects on P. aeruginosa and host cells. Our results suggest that bacterial OL plays important roles in bacteria-host interaction in a way that enhances bacterial persistence and develops chronic adaptation to infection.

Treatment of a mandibular discontinuity defect by using a fibula free flap and an implant-supported fixed complete denture fabricated with a PEKK framework: A clinical report.

This clinical report describes the rehabilitation of a patient with a history of mandibulectomy that involved the use of a fibula free flap and an implant-supported fixed complete denture. A recently introduced material, polyetherketoneketone (PEKK), was used as the framework material for the prosthesis, and the treatment produced favorable esthetic and functional results.

Evaluation of the fit of zirconia copings fabricated by direct and indirect digital scanning procedures.

STATEMENT OF PROBLEM: Intraoral scanners are effective for direct digital scans when dental restorations are fabricated using computer-aided design and computer-aided manufacturing (CAD-CAM); however, if the abutment tooth cannot be dried completely or the prepared margin is placed subgingivally, accurate digital images cannot always be guaranteed. PURPOSE: The purpose of this in vitro study was to compare the internal and marginal discrepancies of zirconia copings fabricated directly using an intraoral scanner with those fabricated indirectly with impression scanning. MATERIAL AND METHODS: Forty-five resin dies fabricated with a 3-dimensional (3D) printer were divided into 3 groups: direct scanning (DS), impression scanning (IMP), and lost-wax casting (LW). For the DS group, a resin die was scanned with an intraoral scanner (Trios; 3Shape), whereas for the IMP group, impressions made with polyether were scanned with a cast scanner (D700; 3Shape). The zirconia copings were fabricated in the same way in the DS and IMP groups. For the LW group, impressions were made in the same way as in the IMP group, and Ni-Cr alloy copings were fabricated using LW. The marginal and internal discrepancies of the copings were measured by cementing them onto resin dies, embedding them in acrylic resin, and sectioning them in a buccolingual direction. The cement layer was measured, and the Kruskal-Wallis test was used to detect significant differences (α=.05). A nonparametric Friedman test was also performed to compare the measurements of each group by location (α=.05). RESULTS: The mean marginal discrepancies in the DS, IMP, and LW groups were 18.1 ±9.8, 23.2 ±17.2, and 32.3 ±18.6 µm (mean ±standard deviation), respectively. The mean internal discrepancies of the DS, IMP, and LW groups in the axial area were 38.0 ±9.1, 47.0 ±16.3, and 36.5 ±15.8 µm, and those in the occlusal area were 36.7 ±16.9, 33.4 ±21.6, and 44.5 ±31.9 µm, respectively. No statistically significant differences were found in marginal or internal discrepancies among groups (P>.05). CONCLUSIONS: Within the limitations of this study, the zirconia copings fabricated with CAD-CAM using different digitization methods and Ni-Cr copings fabricated using the lost-wax technique and casting produced clinically acceptable marginal and internal discrepancies. No significant differences were found among the DS, IMP, and LW groups.

Antibacterial activities of viriditoxin congeners and synthetic analogues against fish pathogens.

Viriditoxin is a fungal secondary metabolite of the fungus Paecilomyces variotii derived from the inner tissues of the giant jellyfish Nemopilema nomurai. Viriditoxin exhibits antibacterial activity against Streptococcus iniae and Streptococcus parauberis, which are major pathogens of aqua cultured fish. Viriditoxin induced abnormal cell morphologies in the fish pathogens S. iniae and S. parauberis, presumably by inhibiting FtsZ polymerization as was previously observed in Escherichia coli. Synthetic analogues of viriditoxin, designed based on docking simulation results to FtsZ of Staphylococcus aureus, were prepared and compared with viriditoxin for antibacterial activity. Reconstitution of free hydroxyl or carboxyl groups of the methoxyl or methyl ester groups of viriditoxin led to significant reduction of antibacterial activity, implying that the natural molecule is optimized for antibacterial activity to deter bacteria potentially harmful to Paecilomyces.

The effects of Pilates breathing trainings on trunk muscle activation in healthy female subjects: a prospective study.

[Purpose] To investigate the effects of Pilates breathing on trunk muscle activation. [Subjects and Methods] Twenty-eight healthy female adults were selected for this study. Participants' trunk muscle activations were measured while they performed curl-ups, chest-head lifts, and lifting tasks. Pilates breathing trainings were performed for 60 minutes per each session, 3 times per week for 2 weeks. Post-training muscle activations were measured by the same methods used for the pre-training muscle activations. [Results] All trunk muscles measured in this study had increased activities after Pilates breathing trainings. All activities of the transversus abdominis/internal abdominal oblique, and multifidus significantly increased. [Conclusion] Pilates breathing increased activities of the trunk stabilizer muscles. Activation of the trunk muscle indicates that practicing Pilates breathing while performing lifting tasks will reduce the risk of trunk injuries.

Effect of maitland mobilization in cervical and thoracic spine and therapeutic exercise on functional impairment in individuals with chronic neck pain.

[Purpose] This study evaluated joint mobilization and therapeutic exercise applied to the cervical spine and upper thoracic spine for functional impairment caused by chronic neck pain. [Subjects and Methods] Eighteen study subjects were randomly assigned to two groups of nine people each. Therapeutic exercise only was applied to the cervical and upper thoracic spine for Group I, while both therapeutic exercise and joint mobilization were applied to Group II. The visual analog scale, neck disability index, active cervical range of motion, static balance capacity, and muscle tone were assessed with a pre-test. The intervention was carried out for 60 minutes a day, three times a week, for two weeks for each group, followed by a post-test using the same protocol as the pre-test. [Results] The visual analog scale, neck disability index, and active cervical range of motion improved significantly in both groups. Group II improved significantly more on right lateral flexion and rightward rotation. Muscle tone improved significantly in the upper trapezius in both groups. [Conclusion] The joint mobilization and therapeutic exercise for functional impairments caused by chronic neck pain had a significant effect on several types of functional impairment.

The effects of pre-exercise vibration stimulation on the exercise-induced muscle damage.

[Purpose] To investigate the effects of pre-induced muscle damage vibration stimulation on the pressure-pain threshold and muscle-fatigue-related metabolites of exercise-induced muscle damage. [Subjects and Methods] Thirty healthy, adult male subjects were randomly assigned to the pre-induced muscle damage vibration stimulation group, post-induced muscle damage vibration stimulation group, or control group (n=10 per group). To investigate the effects of pre-induced muscle damage vibration stimulation, changes in the pressure-pain threshold (lb), creatine kinase level (U/L), and lactate dehydrogenase level (U/L) were measured and analyzed at baseline and at 24 hours, 48 hours, and 72 hours after exercise. [Results] The pressure-pain thresholds and concentrations of creatine kinase and lactate dehydrogenase varied significantly in each group and during each measurement period. There were interactions between the measurement periods and groups, and results of the post-hoc test showed that the pre-induced muscle damage vibration stimulation group had the highest efficacy among the groups. [Conclusion] Pre-induced muscle damage vibration stimulation is more effective than post-induced muscle damage vibration stimulation for preventing muscle damage.

Effects of forward head posture on static and dynamic balance control.

[Purpose] To determine the effects of forward head posture on static and dynamic balance control. [Subjects and Methods] This study included 30 participants who were included into a forward head posture group (n = 14) and a control group (n = 16) according to their craniovertebral angles. Static balance control was assessed according to center of gravity sway velocity and total sway distance using an automatic balance calibration system. Dynamic balance control was assessed using the diagnosis mode of a body-tilt training and measurement system. [Results] Sway velocities on a hard surface with eyes open and closed and those on an unstable sponge surface with eyes closed were significantly higher in the forward head posture group than in the control group. Furthermore, on both the hard and sponge surfaces in the eyes open and closed conditions, total sway distances were significantly higher in the forward head posture group than in the control group. Results of dynamic balance control were not significantly different between groups. [Conclusion] Forward head posture has a greater effect on static balance control than on dynamic balance control.

The effects of shoe heel height and gait velocity on position sense of the knee joint and balance.

[Purpose] The aim of this study was to examine the effects of increased heel height and gait velocity on balance control and knee joint position sense. [Subjects and Methods] Forty healthy adults were randomly allocated to 4 groups: low-heel, low-speed group (3 cm, 2 km/h), low-heel, high-speed group (3 cm, 4 km/h), high-heel, low-speed group (9 cm, 2 km/h), high-heel, and high-speed group (9 cm, 4 km/h), with 10 subjects per group. Static and dynamic balance was evaluated using the I-Balance system and knee joint position sense using a goniometer. Measurements were compared using a pre- and posttest design. [Results] Increasing heel height and gait velocity decreased knee joint position sense and significantly increased the amplitude of body sway under conditions of static and dynamic balance, with highest sway amplitude induced by the high-heel, high-speed condition. [Conclusion] Increased walking speed in high heels produced significant negative effects on knee joint sense and balance control.

Protease IV, a quorum sensing-dependent protease of Pseudomonas aeruginosa modulates insect innate immunity.

In Pseudomonas aeruginosa, quorum sensing (QS) plays an essential role in pathogenesis and the QS response controls many virulence factors. Using a mealworm, Tenebrio molitor as a host model, we found that Protease IV, a QS-regulated exoprotease of P. aeruginosa functions as a key virulence effector causing the melanization and death of T. molitor larvae. Protease IV was able to degrade zymogens of spätzle processing enzyme (SPE) and SPE-activating enzyme (SAE) without the activation of the antimicrobial peptide (AMP) production. Since SPE and SAE function to activate spätzle, a ligand of Toll receptor in the innate immune system of T. molitor, we suggest that Protease IV may interfere with the activation of the Toll signaling. Independently of the Toll pathway, the melanization response, another innate immunity was still generated, since Protease IV directly converted Tenebrio prophenoloxidase into active phenoloxidase. Protease IV also worked as an important factor in the virulence to brine shrimp and nematode. These results suggest that Protease IV provides P. aeruginosa with a sophisticated way to escape the immune attack of host by interfering with the production of AMPs.