Association of Muscle Strength and Gait Speed with Cross-Sectional Muscle Area Determined by Mid-Thigh Computed Tomography - A Comparison with Skeletal Muscle Mass Measured by Dual-Energy X-Ray Absorptiometry.

BACKGROUND: Muscle mass is often mentioned not to reflect muscle strength. For muscle mass assessment skeletal muscle index (SMI) is often used. We have reported that dual-energy X-ray absorptiometry (DXA)-derived SMI does not change with age in women, whereas the cross-sectional muscle area (CSMA) derived from computed tomography (CT) does. OBJECTIVES: The present study aimed to compare CT and DXA for the assessment of muscle tissue. DESIGN AND SETTING: Cross-sectional study in the local residents. PARTICIPANTS: A total of 1818 subjects (age 40-89 years) randomly selected from community dwellers underwent CT examination of the right mid-thigh to measure the cross-sectional muscle area (CSMA). Skeletal muscle mass (SMM) was measured by DXA. The subjects performed physical function tests such as grip strength, knee extension strength, leg extension strength, and gait speed. The correlation between CT-derived CSMA and DXA-derived SMM along with their association with physical function was examined. RESULTS: After controlling for related factors, the partial correlation coefficient of muscle cross-sectional area (CSA) with physical function was larger than that of DXA-derived SMM for gait speed in men (p=0.002) and knee extension strength in women (p=0.03). The partial correlation coefficient of quadriceps (Qc) CSA with physical function was larger than that of DXA-derived SMM for leg extension power in both sexes (p=0.01), gait speed in men (p<0.001), and knee extension strength in women (p<0.001). CONCLUSION: Mid-thigh CT-derived CSMA, especially Qc CSA, showed significant associations with grip strength, knee extension strength, and leg extension power, which were equal to or stronger than those of DXA-derived SMM in community-dwelling middle-aged and older Japanese people. The mid-thigh CSMA may be a predictor of mobility disability, and is considered to be useful in the diagnosis of sarcopenia.

Roles of histone H3.5 in human spermatogenesis and spermatogenic disorders.

Histone H3.5 (H3.5) is a newly identified histone variant highly expressed in the human testis. We have reported the crystal structure, instability of the H3.5 nucleosome and accumulation around transcription start sites, mainly in primary spermatocytes, but its role in human spermatogenesis remains poorly understood. Testicular biopsy specimens from 30 men (mean age: 35 years) with non-obstructive azoospermia (NOA) who underwent microdissection testicular sperm extraction and 23 men with obstructive azoospermia (OA) were included. An H3.5-specific mouse monoclonal antibody recognizing an H3.5-specific synthetic peptide was generated, and immunohistological staining for H3.5 and proliferating cell nuclear antigen (PCNA) was performed on Bouin's solution-fixed sections. Expression and localization of H3.5 were compared with patient background, germinal stage, and PCNA expression. In testes of patients with normal spermatogenesis, differentially expressed H3.5 was specifically localized in either spermatogonia or preleptotene/leptotene-stage primary spermatocytes, especially during germinal stages VI-X. In NOA testes, mRNA expression of H3.5 (H3F3C) was significantly reduced compared with other H3 histone family members, and expression of H3.5 was significantly lower than that in OA. Additionally, the number of H3.5-positive germ cells was higher in hypospermatogenesis or late maturation arrest than in early maturation arrest in NOA testes (p < 0.01). A significant positive correlation was observed between H3.5 and PCNA expression (p < 0.05) but not TUNEL-positive cells, and expression of H3.5 was enhanced after hCG-based salvage hormonal therapy. Different from other testis-specific histones, which are often expressed during the histone-to-protamine transition during meiosis, H3.5 was expressed mainly in immature germ cells. H3.5 may play roles in DNA synthesis, but not apoptosis, and its expression is regulated by gonadotropins, indicating that such epigenetic regulations are important in normal spermatogenesis and spermatogenic disorders.

Effect of low-temperature degradation on the mechanical and microstructural properties of tooth-colored 3Y-TZP ceramics.

The aim of the present study was to evaluate the effects of low-temperature degradation (LTD) induced by autoclaving on the mechanical and microstructural properties of tooth-colored 3 mol% yttria-stabilized tetragonal zirconia polycrystals (3Y-TZP). In total, 162 disc-shaped 3Y-TZP specimens were prepared. Two-thirds of the specimens were shaded by either the infiltration or powder mixing methods while the remaining specimens were used without coloring. The specimens were autoclaved at 134 °C for 0, 10, and 100 h to induce LTD (n=18 for each group). Chemical compositions were analyzed with X-ray fluorescence spectroscopy. Biaxial flexural strength was measured using a piston-on-three-ball test. The surface fraction and penetration depth of the monoclinic phase were examined using X-ray diffraction and scanning electron microscopy, respectively. The tooth-colored 3Y-TZP specimens contained Fe2O3 and Er2O3 (infiltration technique), and Fe2O3 (powder mixing method) at concentrations of<0.5 wt%. The tooth-colored 3Y-TZP had higher strength than the non-colored material after 100 h of autoclaving. In terms of surface fraction and penetration depth, the generation of monoclinic phase was significantly lower in the tooth-colored 3Y-TZP than in the non-colored material. The tooth-colored 3Y-TZP possessed equivalent biaxial flexural strength to that of the non-colored material and higher resistance to LTD regardless of the coloring technique (infiltration technique or powder mixing method) when the coloring pigments were contained at concentrations used in the present study.

The influence of low-temperature degradation and cyclic loading on the fracture resistance of monolithic zirconia molar crowns.

The present study analyzed the kinetics of low-temperature degradation (LTD) in zirconia, and evaluated the influence of LTD and cyclic loading on the fracture resistance of monolithic zirconia molar crowns. Bar-shaped zirconia specimens were divided into nine groups and autoclaved at 134°C for 0-200h to induce LTD. The surface fraction and penetration depth of the monoclinic phase were examined using X-ray diffraction and scanning electron microscopy. Monolithic zirconia molar crowns were prepared for crown fracture testing. The crowns were autoclaved for 0-100h (n=6) and cemented to dies. Six crown-die samples that were not autoclaved and six samples that were autoclaved for 100h were subjected to cyclic loading with a load of 300N for 240,000 cycles. All samples were tested in a load-to-failure test. The monoclinic fraction on the surface increased with autoclaving time and reached a plateau after 50h. The depth of the monoclinic phase increased without reaching a plateau. The fracture load of the crowns significantly decreased from 5683N (SD: 342) to 3975N (SD: 194) after 100h of autoclaving. Cyclic loading did not significantly affect the fracture resistance of the crowns in all cases. Kinetic analysis showed no linear correlation between the surface fraction and depth of the monoclinic phase after 50h of autoclaving. Even though LTD increased the monoclinic phase, resulting in lower strength, the fracture resistance of the monolithic zirconia crowns was still sufficient to withstand the loading conditions in the molar regions.

Classification of women with and without hip fracture based on quantitative computed tomography and finite element analysis.

UNLABELLED: We used quantitative computed tomography and finite element analysis to classify women with and without hip fracture. Highly accurate classifications were achieved indicating the potential for these methods to be used for subject-specific assessment of fracture risk. INTRODUCTION: Areal bone mineral density (aBMD) is the current clinical diagnostic standard for assessing fracture risk; however, many fractures occur in people not defined as osteoporotic by aBMD. Finite element (FE) analysis based on quantitative computed tomography (QCT) images takes into account both bone material and structural properties to provide subject-specific estimates of bone strength. Thus, our objective was to determine if FE estimates of bone strength could classify women with and without hip fracture. METHODS: Twenty women with femoral neck fracture and 15 women with trochanteric fractures along with 35 age-matched controls were scanned with QCT at the hip. Since it is unknown how a specific subject will fall, FE analysis was used to estimate bone stiffness and bone failure load under loading configurations with femoral neck internal rotation angles ranging from -30° to 45° with 15° intervals. Support vector machine (SVM) models and a tenfold cross-validation scheme were used to classify the subjects with and without fracture. RESULTS: High accuracy was achieved when using only FE analysis for classifying the women with and without fracture both when the fracture types were pooled (82.9 %) and when analyzed separately by femoral neck fracture (87.5 %) and trochanteric fracture (80.0 %). The accuracy was further increased when FE analysis was combined with volumetric BMD (pooled fractures accuracy, 91.4 %) CONCLUSIONS: While larger prospective studies are needed, these results demonstrate that FE analysis using multiple loading configurations together with SVM models can accurately classify individuals with previous hip fracture.

A New Grip Strength Measuring Device for Detailed Evaluation of Muscle Contraction among the Elderly.

BACKGROUND: We developed a new grip strength measuring device, which considers the time axis, for evaluating muscle contraction in detail in elderly people. OBJECTIVES: To present the novel device and preliminary results concerning agility in gripping. DESIGN: Cross-sectional analysis. PARTICIPANTS: One hundred and twenty-one older persons (48 men and 73 women, mean age 74.4 years) referring for memory disorders to the outpatient clinic of our institute. MEASUREMENTS: A novel device taking advantage of an industrial force-gauge was developed for measuring gripping performance. The instrument graphically described participants' strength production. Nine indices were derived from four points identified by the graph: 1) starting point ("Go signal"), 2) time when gripping starts, 3) turning point (TP) when the inclination of the curve depicting strength production changes, and 4) peak of strength production. Results obtained from the study sample of older persons were compared (as ratios) to a control group of 30 healthy young adults in their thirties in order to calculate age-related decline rates. Differences between right and left side were compared. RESULTS: A significant difference was observed between right and left hands concerning the time to reach peak of strength, and time from TP to strength peak in both men and women. For women, the following indices were also significantly different: time to reach TP, strength at TP, time from TP to strength peak, curve inclination from TP to strength peak, and ratio of TP strength divided by peak strength. CONCLUSION: Declines in several indices of gripping agility were measured. The parameters which were more closely related to time than strength itself showed significant differences between right and left hands, especially in women.

Occurrence of selected pharmaceuticals in river water in Japan and assessment of their environmental risk.

The existence of pharmaceuticals in the water environment is thought to be a potential problem for aquatic organisms. In this study, we conducted a nationwide survey to clarify the occurrence of 24 selected pharmaceuticals in major Japanese rivers and evaluated their environmental risk to aquatic organisms. We found a total of 22 substances in river waters at concentrations from several nanograms per liter to several micrograms per liter. We found the highest, which was 2.4 µg/L of caffeine, followed by 1.5 µg/L of crotamiton and 1.4 µg/L of sulpiride. We conducted an environmental risk assessment of the 22 pharmaceuticals detected in river water, for which predicted no-effect concentration (PNEC) values for crustacea and algae had been obtained. The measured environmental concentration/PNEC values of four substances, caffeine, carbamazepine, clarithromycin, and ketoprofen, exceeded 0.1 with the maximum value of 9.0 for clarithromycin. As clarithromycin exhibits a high environmental risk to aquatic organisms, particular attention is required.

[Resection of malignant fibrous histiocytoma through a combined thoracic and abdominal wall approach].

We report a case of resection of malignant fibrous histiocytoma (MFH) via combined thoracic and abdominal wall incision reconstructed using GORE DUALMESH. A 60-year-old woman underwent resection of a left lower chest wall tumor. Since the tumor infiltrated into the diaphragm, a part of the left diaphragm and left upper abdominal wall were resected together. The left chest was closed by suturing the diaphragm to the ribs. The resected area of the thoracic and abdominal wall was 12×12 cm and was reconstructed with GORE DUALMESH. She received adjuvant radiotherapy as the tumor cells were detected in the surgical margin of the diaphragm. The patient has remained well without signs of recurrence for 10 months after the operation.

Insecticidal activity of Piper essential oils from the Amazon against the fire ant Solenopsis saevissima (Smith) (Hymenoptera: Formicidae).

Pepper plants in the genus Piper (Piperales: Piperaceae) are common in the Brazilian Amazon and many produce compounds with biological activity against insect pests. We evaluated the insecticidal effect of essential oils from Piper aduncum, Piper marginatum (chemotypes A and B), Piper divaricatum and Piper callosum against workers of the fire ant Solenopsis saevissima (Smith) (Hymenoptera: Formicidae), as well as their chemical composition by gas chromatography and gas chromatography-mass spectrometry. The lowest median lethal concentration (LC50) in 48 h was obtained with the oil of P. aduncum (58.4 mg/L), followed by the oils of P. marginatum types A (122.4 mg/L) and B (167.0 mg/L), P. divaricatum (301.7 mg/L), and P. callosum (312.6 mg/L). The major chemical constituents were dillapiole (64.4%) in the oil of P. aduncum; p-mentha-1(7),8-diene (39.0%), 3,4-methylenedioxypropiophenone (19.0%), and (E)-ß-ocimene (9.8%) in P. marginatum chemotype A and (E)-isoosmorhizole (32.2%), (E)-anethole (26.4%), isoosmorhizole (11.2%), and (Z)-anethole (6.0%) in P. marginatum chemotype B; methyleugenol (69.2%) and eugenol (16.2%) in P. divaricatum; and safrole (69.2%), methyleugenol (8.6%), and ß-pinene (6.2%) in P. callosum. These chemical constituents have been previously known to possess insecticidal properties.

[Negative pressure wound therapy was useful in treating empyema with bronchopleural fistula].

We report a case for whom negative pressure wound therapy (NPWT) was applied for empyema with bronchopleural fistula. The patient was a 64-year-old man with a history of gastric resection and diabetes visited our hospital with chief complaints of fever and respiratory failure. In spite of conservative treatment after being diagnosed as empyema, bronchopleural fistula developed. In order to manage the pyothorax, the bronchopleural fistula was closed with endobronchial Watanabe spigot, and fenestration was subsequently performed, however the infection control and obliteration of the empyema cavity could not be achieved. NPWT with continuous irrigation was therefore chosen, and the methicillin-resistant Staphylococcus aureus (MRSA) disappeared and a marked obliteration of the empyema cavity was observed in 3 weeks after initiation of NPWT. Although the patient died of another illness, NPWT with continuous irrigation was useful in treating empyema with bronchopleural fistula.

A novel nonsecosteroidal VDR agonist (CH5036249) exhibits efficacy in a spontaneous benign prostatic hyperplasia beagle model.

To date, there have been no reports showing the efficacy of nonsecosteroidal vitamin D receptor (VDR) agonists in a benign prostatic hyperplasia (BPH) animal model. To examine the efficacy of CH5036249, a novel nonsecosteroidal VDR agonist, we orally administered the compound at 0.03 microg/kg to a beagle model with spontaneous BPH. Prostate volume was checked by rectal ultrasonic probe periodically during 11 months of administration and the prostate tissues histologically examined. CH5036249 inhibited prostate growth in two out of three dogs compared with vehicle-treated dogs. In the prostate specimens, substantial atrophy of the epithelium was observed in all dogs administered CH5036249. At the dose given, serum calcium levels slightly increased in the CH5036249-treated dogs but stayed within a normal range. We next examined the cell growth inhibition of CH5036249 using human prostate stromal cells and found the cell growth inhibitory activity of CH5036249 to be comparable to that of 1alpha,25(OH)2D3. The bioavailability from oral administration in rats was 95.1% with a t1/2 of 17.6 h. Both micro-AMES and micronucleus tests were negative. Although the results are still preliminary, we consider the novel nonsecosteroidal VDR agonist CH5036249 to be a possible new drug candidate for the treatment of BPH in humans.

Quasi-two-dimensional Fermi surfaces and coherent interlayer transport in KFe2As2.

We report the results of the angular-dependent magnetoresistance oscillations (AMROs), which can determine the shape of bulk Fermi surfaces (FSs) in quasi-two-dimensional (Q2D) systems, in a highly hole-doped Fe-based superconductor KFe2As2 with Tc ≈ 3.7 K. From the AMROs, we determined the two Q2D FSs with rounded-square cross sections, correspond to 12% and 17% of the first Brillouin zone. The rounded-squared shape of the FS cross section is also confirmed by the analyses of the interlayer transport under in-plane fields. From the obtained FS shape, we infer the character of the 3d orbitals that contribute to the FSs.

Raloxifene enhances spontaneous microaggregation of platelets through upregulation of p44/p42 MAP kinase: a case report.

UNLABELLED: A 60-year-old postmenopausal woman diagnosed as primary osteoporosis began to take raloxifene. The spontaneous microaggregates of platelets induced by shear stress were accelerated after the treatment, concomitant with the significant upregulation of p44/p42 mitogen-activated protein (MAP) kinase induced by adenosine diphosphate (ADP). After the cessation of raloxifene, the spontaneous microaggregates of platelets and the acceleration of ADP-induced p44/p42 MAP kinase phosphorylation was diminished. We concluded that raloxifene caused platelet hyperaggregability to shear stress and p44/p42 MAP kinase was involved in the pathological state. INTRODUCTION: A 60-year-old postmenopausal woman suffering from severe lumbago was diagnosed as primary osteoporosis with combined vertebral fractures. After the acute phase, she began to take 60 mg daily of oral raloxifene. The spontaneous microaggregates of platelets induced by shear stress were accelerated significantly after 8 weeks from the beginning of raloxifene treatment and observed at 12 weeks. RESULTS: The platelet aggregation induced by ADP was little changed; however, low doses (0.3 and 1 microM) of ADP significantly induced the phosphorylation of p44/p42 MAP kinase in the platelets obtained at 12 weeks. Although there were few subjective complaints except for paroxysmal headache, the medication was stopped with her consent to avoid any adverse effects. The spontaneous microaggregates of platelets gradually decreased after the cessation of medication. At 12 weeks after the cessation, the phosphorylation of p44/p42 MAP kinase induced by low doses of ADP was no more observed. CONCLUSION: These results strongly suggest that raloxifene caused platelet hyperaggregability to shear stress and subclinical thrombus formation in this case and that p44/p42 MAP kinase was involved in the pathological state.

Pulmonary capillary embolism caused by cryptococcemia in a hemodialysis patient.

In this report, we describe a patient who contracted fatal cryptococcosis after the induction of hemodialysis. A 76-year-old man was hospitalized to initiate hemodialysis. On admission, clinical findings showed no signs of any infections, and hemodialysis was inducted favorably. On the 6th hospital day he suddenly had a dyspnea and died from acute respiratory failure having a dyspnea for only 6 h. By microscopic examination at autopsy, we detected microemboli in the pulmonary capillary arteries caused by Cryptococcus and that the embolic source was a multiple-abscessed spleen. To the best of our knowledge, this is the first reported case of pulmonary capillary microembolism caused by cryptococcemia.

Tetracycline-inducible promoter-based conditionally replicative adenoviruses for the control of viral replication.

The use of conditionally replicative adenoviruses (CRAds) as a promising strategy for cancer gene therapy has been developed to overcome inefficient transduction of solid tumor masses by replication-deficient adenoviruses. Many modifications have been made to CRAds to enlarge tropism, increase selectivity and lytic ability, and improve safety. However, safety is still a concern in the context of future clinical application of CRAds. Particularly, after injection into the body, viral replication cannot be controlled externally. Therefore, we constructed a novel CRAd using a tetracycline-inducible promoter system to realize external pharmacological control of its replication. The effect of this CRAd in vitro was measured at the levels of viral DNA replication, cell death and progeny production. We showed that CRAd replication was tightly controlled by the presence or absence of doxycycline (Dox). Moreover, this system showed a significant gene expression in vivo, in which the viral replication was controlled by the oral administration of Dox. This strategy may help improve the safety of cancer gene therapy.

Reconstruction of carbon atoms around a point defect of a graphene: a hybrid quantum/classical molecular-dynamics simulation.

We have investigated the rearrangement of carbon atoms around a point defect of a graphene using a hybrid ab initio/classical molecular-dynamics (MD) simulation method, in which 36 carbon atoms surrounding a point defect are treated by the ab initio MD method and the other 475 carbon atoms relatively far from the point defect are treated by the classical MD method. We have confirmed a formation of a 5-1DB defect (a pentagon and a dangling bond) from the time dependence of atomic configurations and electron density distributions obtained by our simulation. We have found that the pentagon is formed in two different positions around the point defect, and that the two positions appear alternately during the simulation, the frequency of which increases with increasing temperature.

(-)-Epigallocatechin gallate inhibits basic fibroblast growth factor-stimulated interleukin-6 synthesis in osteoblasts.

We previously showed that basic fibroblast growth factor (FGF-2) activates the mitogen-activated protein (MAP) kinase superfamily in osteoblast-like MC3T3-E1 cells and that p38 MAP kinase functions as a positive regulator in the FGF-2-stimulated synthesis of interleukin-6 (IL-6), a potent bone-resorptive agent, in these cells. In the present study, we investigated the exact mechanism of IL-6 and the effects of (-)-epi-gallocatechin gallate (EGCG), one of the major green tea flavonoids, on the synthesis of IL-6. PD98059, an inhibitor of MEK, but not SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase, suppressed FGF-2-stimulated IL-6 synthesis. EGCG significantly reduced the IL-6 synthesis stimulated by FGF-2 in a dose-dependent manner. EGCG attenuated the FGF-2-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase. These results strongly suggest that EGCG inhibits the FGF-2-stimulated synthesis of IL-6 at least partly via suppression of the p44/p42 MAP kinase pathway and the p38 MAP kinase pathway in osteoblasts.