Gait-related self-efficacy is directly associated with daily step counts in individuals with knee osteoarthritis.

BACKGROUND: In addition to physical factors, psychological factors such as self-efficacy (SE) reportedly affect physical activity (PA) levels in individuals with knee osteoarthritis (OA). However, the relationship between PA and SE for walking tasks in patients with knee OA remains unclear. The present study aimed to investigate the direct and indirect pathways of SE for walking tasks and the influence of previously reported factors on PA level in individuals with knee OA. METHODS: A cross-sectional design was employed. Eighty-five individuals with knee OA were enrolled. The daily step count (Steps) was considered an objective level of PA. The SE for the walking task was assessed using a modified Gait Efficacy Scale (mGES). Data on gait speed (GS), the visual analog scale (VAS) score for knee pain, Kellgren-Lawrence (K-L) grade of radiographic severity of knee OA, age, and body mass index were collected. Path analysis was performed to investigate the direct and indirect effects of these variables on Steps. RESULTS: After exclusion, 70 participants were included. The alternative model, which included Steps, mGES, GS, VAS, K-L grade, and age, showed a good fit. mGES and age had a direct effect on Steps (standardized path coefficients: 0.337 and -0.542, respectively), while the other variables had indirect effects. CONCLUSIONS: The SE for walking tasks was directly associated with Steps representative of the PA level. This finding suggests that SE for the walking task may be important in improving PA levels in individuals with knee OA.

Gait-related Self-efficacy is Low in Older Adults with Knee Osteoarthritis: A Preliminary Study.

OBJECTIVE: To investigate the differences in self-efficacy (SE) for walking tasks between older patients with knee osteoarthritis (OA) and older adults without knee OA. METHODS: A cross-sectional design was employed. Older patients with radiographic knee OA and community-dwelling older adults without knee OA as controls were enrolled in the study. SE for the walking task was assessed using the modified gait efficacy scale (mGES). A Wilcoxon rank-sum test was used to compare the mGES between the groups of participants. A Tobit regression model was used to estimate the difference in mGES. The presence of radiographic knee OA was used as an independent variable. Sex (women), age, and body mass index were used as potential confounding variables in the model. RESULTS: After exclusion, 78 participants (n=40 with knee OA, n=38 controls) were included. The mGES was lower in patients with knee OA than in controls. In the Tobit regression model adjusted for confounding factors, mGES in patients with knee OA was estimated to be 26.8 (95% confidence interval [CI]: 15.8-37.8) points lower than in controls. CONCLUSION: This study demonstrated that mGES was lower in older patients with knee OA than in older adults without knee OA.

Fibrin monomer complex on postoperative day 1 is correlated with the volume of deep vein thrombosis after knee surgery.

PURPOSE: Patients undergoing knee surgery are at high risk for deep vein thrombosis (DVT), which is infrequent but potentially life-threatening. It has not been identified how to efficiently detect high-risk DVT while minimizing bleeding complications from anticoagulation. We hypothesized that the degree of activation of thrombotic markers may correlate with the size of the thrombus. Therefore, we investigated the correlation between thrombotic markers and DVT thrombus volume in patients after knee surgery. METHODS: This retrospective study involved 29 patients who underwent around knee osteotomy or total / unicompartmental knee arthroplasty from 2018 to 2020. Fibrin monomer complex (FMC) at 1, and 7 days after surgery, and D-dimer at 4, and 7 days after surgery were investigated. In addition, the volume of DVT was estimated with ultrasonography at the 7 days after surgery. Body mass index, surgical time, and total volume of blood loss were also evaluated. Factors related to thrombus volume were examined statistically. RESULTS: Nine patients (31.0%) exhibited asymptomatic distal DVT, whereas 1 patient (3.4%) experienced asymptomatic proximal DVT. No patients had pulmonary embolism. Statistical analysis showed that only FMC concentration on postoperative day 1 was significantly correlated with thrombus volume (p <  0.001, 95% confidence interval 0.41 to 0.839, r = 0.679). CONCLUSIONS: The FMC concentration was a useful early indicator of deep vein thrombosis after knee surgery. Monitoring the FMC concentration could enable selective identification of patients with a high thrombus volume, which is associated with a high risk for pulmonary embolism.

Hyperechoic and Low Morphological Changes in the Prefemoral Fat Pad in Individuals with Knee Osteoarthritis Based on Ultrasonographic Findings.

BACKGROUND: To clarify the changes in the echo intensity (EI) in the prefemoral fat pad (PFP) and identify the relationship between the PFP and clinical features of knee osteoarthritis (OA). METHODS: Twenty-six women with knee OA (mean age: 76 years) and 17 healthy women (mean age: 73 years) were enrolled. The Kellgren and Lawrence grading scale was used for the radiographic evaluation of knee OA. The EI of the PFP was measured as grayscale values. The change ratio of the anteroposterior PFP length during quadriceps contraction was measured. Knee range of motion and pain (100-mm visual analog scale) were evaluated. RESULTS: The EI was significantly higher in the OA group than in the healthy group (P < 0.001). The change ratio of the PFP in the OA group was significantly lower than that in the healthy group (P < 0.001). The ranges of knee flexion and extension were correlated with the EI of the PFP (both P < 0.01) and the change ratio of the PFP (both P < 0.01). There was no significant correlation observed with knee pain. CONCLUSION: Hyperechoic changes and a decreased change ratio of the PFP were observed in the patients with knee OA. High EI and decreased morphological PFP changes were associated with decreased ranges of motion.

Snapping Pes Syndrome Caused by the Gracilis Tendon: Successful Selective Surgery with Specific Diagnosis by Ultrasonography.

We report the case of painful snapping pes syndrome caused by the gracilis tendon. A 26-year-old man presented with acute right knee pain and restricted extension. Although snapping could not be reproduced due to severe pain, the snapping of the gracilis tendon could be specifically diagnosed using ultrasonography and lidocaine injection. Because of the failure of conservative treatment, surgery was performed. The distal attachment of the gracilis tendon was released, and the symptom disappeared quickly. There was no recurrence at the 10-month follow-up.

Ultrasonographic Morphological Changes in the Prefemoral Fat Pad Associated with Knee Osteoarthritis.

BACKGROUND: In normal knees, quadriceps contraction changes the shape of the prefemoral fat pad (PFP). However, in persons with knee osteoarthritis (OA), the functional or morphological changes of the PFP are unclear. This study aimed to clarify the morphological changes in the PFP in individuals with knee OA through ultrasonography. MATERIALS AND METHODS: Participants were divided into the OA (36 knees; mean age, 74 years), elderly (31 knees; mean age, 70 years), and young (26 knees; mean age, 21 years) groups. The anteroposterior (AP) length of the PFP before and during isometric quadriceps contraction at 0°, 30°, 60°, and 90° knee flexion was measured ultrasonographically. The difference between the maximum and minimum length values, change in length, was also measured. These parameters were compared among the three groups. In the OA group, correlations between the parameters and clinical features (knee pain; visual analog scale, knee range of motion [ROM], Kellgren and Lawrence (K/L) grade, and intercondylar distance) were examined by Spearman and Pearson's correlation coefficient tests. RESULTS: The AP lengths of the PFP before contraction were significantly lower in the OA group than in elderly group and young group at 30° (6.9 ± 2.5 vs. 12.0 ± 3.6 or 11.1 ± 2.7 mm, respectively; in order P = 0.014, P = 0.006) and 60° (6.5 ± 2.0 vs. 9.7 ± 2.5 or 9.1 ± 2.7 mm, respectively; both P < 0.001). The AP lengths of the PFP during contraction were significantly lower in the OA group than in elderly group and young group at 0° (6.7 ± 2.3 vs. 8.8 ± 3.7 or 9.1 ± 1.6 mm, respectively; both P < 0.001), 30° (7.9 ± 2.6 vs. 12.9 ± 3.7 or 13.0 ± 2.6 mm, respectively; both P < 0.001), and 60° (7.1 ± 2.5 vs. 13.5 ± 2.6 or 13.6 ± 3.0 mm, respectively; both P < 0.001). The change in length before maximum isometric quadriceps contraction was significantly lower in the knee OA group than in both elderly and young groups (3.3 ± 1.9 vs. 8.4 ± 2.5 or 6.8 ± 3.0 mm, respectively; both P < 0.001). The change in length during contraction was also significantly lower in the knee OA group than in both the elderly and young groups (3.9 ± 2.3 vs. 8.7 ± 2.3 or 8.9 ± 2.0 mm, respectively; both P < 0.001). In the OA group, change in length during contraction was significantly associated with knee pain (r = -0.476, P = 0.007), knee ROM (r = 0.388, P = 0.019), and Kellgren and Lawrence grade (r = -0.357, P = 0.045). CONCLUSIONS: In knee OA, movement of PFP was decreased more than healthy participants. In the knee OA group, the decrease of the morphological change of the PFP showed the relationship between VAS score, knee extension ROM, intercondylar distance (ICD), and K/L grade. An evaluation to the PFP may be required in individuals with knee OA.

Pharmacokinetics of Morphine in Rats with Adjuvant-induced Arthritis.

We investigated the in vivo dynamics and analgesic effect of morphine using an adjuvant-induced arthritis (AA) rat as a model of chronic inflammation. Morphine generally binds to µ-opioid receptors in the brain to exert its effects. After several minutes, it is metabolized by glucuronidation via a UDP-glucuronosyltransferase (UGT). Here, we showed that in AA rats, UGT activity in liver microsomes was reduced. Morphine-free serum fractions in AA rats were also decreased (control, 84.9%; AA, 63.9%) and the expression of ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1), which plays a crucial role in morphine bile excretion, decreased to 23.0% that of the control group. However, we observed no significant difference between the AA and control groups regarding blood concentrations of morphine and morphine-3-glucuronide. In contrast, the analgesic effect of morphine increased 4-fold in AA rats. Our results showed that the pharmacokinetics of morphine is not changed, but the pharmacodynamics of morphine is enhanced in chronic inflammation.

Influence of the pharmacokinetic profile on the plasma glucose lowering effect of the PPARγ agonist pioglitazone in Wistar fatty rats.

Although the mechanism of action for peroxisome proliferator-activated receptor gamma (PPARγ) agonists has been extensively explored, the impact of the pharmacokinetic (PK) profile on the pharmacodynamic (PD) effects of PPARγ agonists has not been elucidated in detail. The importance of the PK profile of PPARγ agonist was evaluated for its PD effect based on population PK/PD analysis. Pioglitazone hydrochloride, the PPARγ agonist, was administered orally to Wistar fatty rats once a day (q.d.) or once every other day (q.2d.) as double the amount for the q.d. TREATMENT: The plasma glucose lowering effect was selected as a surrogate PD effect for an anti-diabetic effect. The model fitting was conducted using the non-linear mixed effect modeling (NONMEM) method. The indirect response model described well the plasma glucose concentration-time profile. The q.d. treatment showed a stronger impact on the plasma glucose lowering effect than did the q.2d. TREATMENT: The results of PK/PD modeling suggested that the sensitivity (i.e. EC50 ) between each group was comparable. On the other hand, the time above the effective concentration in the q.d. treatment group was longer than that in the q.2d. treatment group. The simulation of various dose regimens suggested that the much longer exposure duration within the effective level showed a stronger plasma glucose lowering effect, even with identical exposure to pioglitazone in the plasma. The PK/PD analysis clarified that the PK profile affected the pharmacological response and that continuous exposure at an appropriate effective level would be efficient for the anti-diabetic effect of the PPARγ agonist.

Prescription rate of medications potentially contributing to lower urinary tract symptoms and detection of adverse reactions by prescription sequence symmetry analysis.

BACKGROUND: The lower urinary tract symptoms (LUTS) increases with age and can have a significant effect on the quality of life of the patients. Elderly patients, who are often characterized by a decline in physiological functional and polypharmacy, are susceptible to adverse drug reactions to pharmacotherapy. LUTS can also be a side effect of medication. The purpose of this study was to investigate the possible association between the initiation of LUTS-causing drug therapy and the onset of LUTS. METHODS: Drug dispensing data at the individual level were retrieved from the CISA (Platform for Clinical Information Statistical Analysis: http://www.cisa.jp) database. A retrospective study was conducted by reviewing patients with LUTS who were dispensed drugs that increased the risk of LUTS between April 2011 and March 2012. Prescription sequence symmetry analysis (PSSA) was employed to investigate the associations between the dispensing of medicines of LUTS and that of LUTS-causing drugs. RESULTS: LUTS-causing drugs were frequently dispensed to patients with LUTS. The use of medications potentially contributing to LUTS was associated with polypharmacy [number of prescription drugs:12.13 ± 6.78 (user) vs. 5.67 ± 5.24 (nonuser)] but not patient age [ age: (71.38 ± 13.28 (user) vs. 70.45 ± 14.80 (nonuser)]. Significant adverse drug events were observed the use of donepezil, cyclophosphamide, antiparkinson drugs, antidepressant, diazepam, antipsychotic drugs for peptic ulcer, tiotropium bromide, and opioids. CONCLUSIONS: The use of prescription LUTS-causing drugs was correlated with polypharmacy. The adverse drug events associated with LUTS-causing drugs were highly prevalent in elderly patients. To prevent of adverse drug events in patients with LUTS, pharmacists and physicians should regularly review medication lists and reduce the prescribed medicines.

Successful treatment of nonunion with an Ilizarov ring fixator after ankle fracture for Charcot arthropathy: a case report.

BACKGROUND: Ankle fractures in patients with diabetes mellitus have long been recognized as a challenge to orthopedic surgeons. Nonunion and lengthy wound healing in high-risk patients with diabetes, particularly patients with peripheral arterial disease and renal failure, occur secondary to several clinical conditions and are often fraught with complications. Whether diabetic ankle fractures are best treated noninvasively or surgically is controversial. CASE PRESENTATION: A 53-year-old Japanese man fractured his right ankle. The fractured ankle was treated nonsurgically with a plaster cast. Although he remained non-weight-bearing for 3 months, radiography at 3 months showed nonunion. The nonunion was treated by Ilizarov external fixation of the ankle. The external fixator was removed 99 days postoperatively, at which time the patient exhibited anatomical and functional recovery and was able to walk without severe complications. CONCLUSION: In patients with diabetes mellitus, severe nonunion of ankle fractures with Charcot arthropathy in which the fracture fragment diameter is very small and the use of internal fixation is difficult is a clinical challenge. Ilizarov external fixation allows suitable fixation to be achieved using multiple Ilizarov wires.

Medication-related factors affecting discharge to home.

To assess the reasons for barriers to home discharge by determining whether they were predicted by medication, clinical variables, and patient characteristics, the retrospective cohort study of 282 patients discharged from Kanazawa Red Cross Hospital in Kanazawa, Japan from January 2011 to December 2012 was performed. The percentage of patients discharged was 67.4%. By multivariate logistic analysis, significant differences in home discharge destination were determined by six factors: the duration of hospitalization before discharge (odds ratio (OR) 0.993; 95% 95% confidence interval (CI) 0.988-0.999), the presence of excretion assistance (OR 0.115; 95% CI 0.043-0.308), individual payment of medical expense (OR 0.344; 95% CI 0.146-0.811), the degree of independent living for the demented elderly (OR4.570; 95% CI 1.969-10.604), presence of the primary caregiver (OR 8.638; 95% CI 3.121-23.906), and admission to a hospital from home (OR 5.483; 95% CI 2.589-11.613). This study suggests that necessity of excretion assistance, long duration of hospitalization, and high individual payment of medical expense were barriers to home discharge. In contrast, three factors i.e., admission to a hospital form home, low degree of independent living for the demented elderly, and presence of the primary caregiver, favored home discharge. The relation between a patient's status (cognitive status and incontinence) and a caregiver has an important effect on the home discharge. However, medication characteristics appeared to have little effect on recuperation destination.

Quantitative investigation of the impact of P-glycoprotein inhibition on drug transport across blood-brain barrier in rats.

The magnitude of P-glycoprotein [(P-gp)/multidrug resistance protein 1 (MDR1)]-mediated drug-drug interaction (DDI) at the blood-brain barrier (BBB) in rats was estimated by in vitro-in vivo correlation (IVIVC). In in vitro studies, rat Mdr1a-expressing LLC-PK1 cells were examined for the evaluation of P-gp inhibitory activity using digoxin as a P-gp probe substrate. The in vitro K(i) value was calculated using a modified corrected flux ratio that reflects the P-gp function. In in vivo studies, digoxin with or without P-gp inhibitors was administered to rats by constant intravenous infusion to evaluate the effect of P-gp inhibition on digoxin transport to the brain under steady-state conditions. In the presence of elacridar, the brain-to-plasma concentration ratio (K(p,brain)) of digoxin was approximately 14 times the control value. However, no significant change in the K(p,brain) was observed in the presence of clinically used P-gp inhibitors, with the exception of cyclosporine A. A positive correlation was found between the in vivo K(p,brain) of digoxin and [I(,unbound)/K(i)] (where I(,unbound) is the unbound plasma concentration of P-gp inhibitors). Compounds with [I(,unbound)/K(i)] values of >1 increased K(p,brain) of digoxin in rats. In summary, we used a quantitative approach to evaluate the impact of P-gp-mediated DDI at the rat BBB. We successfully established the IVIVC, which indicated the potential DDI in the presence of potent P-gp inhibitors. On the basis of the IVIVC in rats and K(i) values in human MDR1, we speculated that clinically used P-gp inhibitors do not cause DDI at the human BBB, because none of the compounds studied showed [I(,unbound)/K(i)] values of >1 at therapeutic doses.

Oseltamivir-resistant influenza a viruses circulating in Japan.

Surveillance studies of the influenza viruses circulating in Europe and other countries in 2007 and 2008 have revealed rates of resistance to oseltamivir of up to 67% among H1N1 viruses. In the present study, we examined 202 clinical samples obtained from patients infected with H1N1 virus in Japan in 2007 and 2008 for oseltamivir resistance and found that three were oseltamivir resistant (1.5%). The 50% inhibitory concentrations (IC(50)s), as measured by a sialidase inhibition assay with these drug-resistant viruses, were >100-fold higher than those of the nonresistant viruses (median IC(50), 12.6 nmol/liter). The His274Tyr (strain N2 numbering) mutation of the neuraminidase protein, which is known to confer oseltamivir resistance, was detected in these three isolates. Phylogenetic analysis showed that one virus belonged to a lineage that is composed of drug-resistant viruses isolated in Europe and North America and that the other two viruses independently emerged in Japan. Continued surveillance studies are necessary to observe whether these viruses will persist.

Asymmetric intestinal first-pass metabolism causes minimal oral bioavailability of midazolam in cynomolgus monkey.

Oral bioavailability of some drugs is substantially lower in cynomolgus monkeys than in various other species, including humans. In the present study, midazolam was used as a model drug to investigate the reason for the lower bioavailability in these monkeys. The bioavailability of midazolam after oral administration was minimal in monkeys and rats, being only 2.1 and 1.1%, respectively. In monkeys, this low bioavailability could not be explained simply in terms of a hepatic first-pass effect. To examine the roles of intestinal metabolism and transport, we evaluated apical-to-basal and basal-to-apical transport of midazolam, and the formation of metabolites in small intestinal tissues using an Ussing-type chamber. The values of mucosal extraction ratio were estimated to be 0.97, 0.93, and 0.89 during apical-to-basal transport in the upper, middle, and lower small intestine of monkeys, respectively, whereas the corresponding values for rats were close to zero, indicating that extensive metabolism of midazolam occurs, particularly in the upper region of the small intestine in monkeys, but not rats. Interestingly, formation of the metabolites was much greater during transport in the apical-to-basal direction than in the basal-to-apical direction, and this could be well explained by a mathematical model based on the assumption that extensive metabolism is associated with the uptake process of midazolam from the apical cell surface. Thus, we conclude that an asymmetric distribution of metabolic activity in the small intestine, leading to extensive metabolism during uptake from the apical cell surface, accounts for the minimal oral bioavailability of midazolam in cynomolgus monkeys.

Crystal structure of the translocation ATPase SecA from Thermus thermophilus reveals a parallel, head-to-head dimer.

The mechanism of pre-protein export through the bacterial cytoplasmic membrane, in which the SecA ATPase plays a crucial role as an "energy supplier", is poorly understood. In particular, biochemical and structural studies provide contradictory data as to the oligomeric state of SecA when it is integrated into the active trans-membrane translocase. Here, we report the 2.8 A resolution crystal structure of the Thermus thermophilus SecA protein (TtSecA). Whereas the structure of the TtSecA monomer closely resembles that from other bacteria, the oligomeric state of TtSecA is strikingly distinct. In contrast to the antiparallel (head-to-tail) dimerization reported previously for the other bacterial systems, TtSecA forms parallel (head-to-head) dimers that are reminiscent of open scissors. The dimer interface is abundant in bulky Arg and Lys side-chains from both subunits, which stack on one another to form an unusual "basic zipper" that is highly conserved, as revealed by homology modeling and sequence analysis. The basic zipper is sealed on both ends by two pairs of the salt bridges formed between the basic side-chains from the zipper and two invariant acidic residues. The organization of the dimers, in which the two pre-protein binding domains are located proximal to each other at the tip of the "scissors", might allow a concerted mode of substrate recognition while the opening/closing of the scissors might facilitate translocation.

Fluorescence resonance energy transfer analysis of protein translocase. SecYE from Thermus thermophilus HB8 forms a constitutive oligomer in membranes.

SecY and SecE are the two principal translocase subunits that create a channel-like pathway for the transit of preprotein across the bacterial cytoplasmic membrane. Here we report the cloning, expression, and purification of the SecYE complex (TSecYE) from a thermophilic bacterium, Thermus thermophilus HB8. Purified TSecYE can be reconstituted into proteoliposomes that function in T. thermophilus SecA (TSecA) dependent preprotein translocation. After the mixing of TSecYE derivatives labeled with either a donor or an acceptor fluorophore during reconstitution, fluorescence resonance energy transfer experiments demonstrated that 2 or more units of TSecYE in the lipid bilayer associate to form a largely non-exchangeable oligomeric structure.