Frequency-domain interferometry for the determination of time delay between two extreme-ultraviolet wave packets generated by a tandem undulator.

Synchrotron radiation, emitted by relativistic electrons traveling in a magnetic field, has poor temporal coherence. However, recent research has proved that time-domain interferometry experiments, which were thought to be enabled by only lasers of excellent temporal coherence, can be implemented with synchrotron radiation using a tandem undulator. The radiation generated by the tandem undulator comprises pairs of light wave packets, and the longitudinal coherence within a light wave packet pair is used to achieve time-domain interferometry. The time delay between two light wave packets, formed by a chicane for the electron trajectory, can be adjusted in the femtosecond range by a standard synchrotron technology. In this study, we show that frequency-domain spectra of the tandem undulator radiation exhibit fringe structures from which the time delay between a light wave packet pair can be determined with accuracy on the order of attoseconds. The feasibility and limitations of the frequency-domain interferometric determination of the time delay are examined.

Changes in the blood level, efficacy, and safety of tacrolimus in pregnancy and the lactation period in patients with systemic lupus erythematosus.

OBJECTIVES: We investigated the efficacy and safety of tacrolimus (TAC) by monitoring its serum concentration for mothers and infants in pregnant patients with systemic lupus erythematosus (SLE). METHODS: We measured trough concentrations of TAC in 25 pregnant patients with SLE to assess influence of TAC on the disease activity. Additionally, we measured the concentrations of TAC in umbilical arterial blood, breast milk, and breastfed infants to investigate the safety of TAC for the mothers and infants. RESULTS: The trough concentrations of TAC in the mothers significantly decreased in the second trimester as compared with those before pregnancy. However, the decrease in the trough concentrations of TAC did not lead to the deterioration of SLE. When examined, the doses of TAC were significantly lower in the second trimester and postpartum in the deteriorating group than those in the non-deteriorating group. There were no adverse events by TAC in mothers and fetuses. The concentrations of TAC in the umbilical cord blood were lower than those in the maternal blood. The relative infant dose in breastfed infants of TAC was < 1%. The level of TAC in infant bloods was below detectable limits. CONCLUSION: These findings suggest that TAC is one of the most effective and safest immunosuppressive drugs for use in pregnant patients with SLE.

Nitrogen Concentrations and Isotopic Compositions of Seafloor-Altered Terrestrial Basaltic Glass: Implications for Astrobiology.

Observed enrichments of N (and the δ15N of this N) in volcanic glasses altered on Earth's modern and ancient seafloor are relevant in considerations of modern global N subduction fluxes and ancient life on Earth, and similarly altered glasses on Mars and other extraterrestrial bodies could serve as valuable tracers of biogeochemical processes. Palagonitized glasses and whole-rock samples of volcanic rocks on the modern seafloor (ODP Site 1256D) contain 3-18 ppm N with δ15Nair values of up to +4.5‰. Variably altered glasses from Mesozoic ophiolites (Troodos, Cyprus; Stonyford volcanics, USA) contain 2-53 ppm N with δ15N of -6.3 to +7‰. All of the more altered glasses have N concentrations higher than those of fresh volcanic glass (for MORB, <2 ppm N), reflecting significant N enrichment, and most of the altered glasses have δ15N considerably higher than that of their unaltered glass equivalents (for MORB, -5 ± 2‰). Circulation of hydrothermal fluids, in part induced by nearby spreading-center magmatism, could have leached NH4+ from sediments then fixed this NH4+ in altering volcanic glasses. Glasses from each site contain possible textural evidence for microbial activity in the form of microtubules, but any role of microbes in producing the N enrichments and elevated δ15N remains uncertain. Petrographic analysis, and imaging and chemical analyses by scanning electron microscopy and scanning transmission electron microscopy, indicate the presence of phyllosilicates (smectite, illite) in both the palagonitized cracks and the microtubules. These phyllosilicates (particularly illite), and possibly also zeolites, are the likely hosts for N in these glasses. Key Words: Nitrogen-Nitrogen isotope-Palagonite-Volcanic glass-Mars. Astrobiology 18, 330-342.

Anatomical study of the inferior patellar pole and patellar tendon.

In this study, detailed investigations into the shape of the inferior patellar pole, the site of the patellar tendon attachment, and the length and course of the patellar tendon were performed with the aim of examining the anatomical factors involved in the developmental mechanism of patellar tendinitis. The investigation examined 100 legs from 50 cadavers. The inferior patellar pole was classified into three types: pointed, intermediate, and blunt. The attachment of the patellar tendon to the inferior patellar pole was classified into two types: an anterior and a posterior. The length of the patellar tendon was measured from the tibial tuberosity to the inferior patellar pole. The pointed type was seen in 57% of legs, the intermediate type in 21%, and the blunt type in 22%. Twenty-one legs were the pointed type, as well as the anterior type. The patellar tendon was significantly shorter with the posterior type than with the anterior type. The blunt type also had a significantly shorter patellar tendon than the pointed type. In legs that were both the pointed type and the anterior type, the inferior patellar pole and the proximal posterior surface of the patellar tendon impinged during knee flexion due to the posterior tilt of the patella, suggesting the possibility that this may induce damage. With the posterior type and blunt type, on the other hand, the possibility of strong tensile stress on the tendon fibers of the posterior facet of the inferior patellar pole was suggested.

MRI T1ρ and T2 mapping for the assessment of articular cartilage changes in patients with medial knee osteoarthritis after hemicallotasis osteotomy.

OBJECTIVES: The purpose of this study was to clarify the appearance of the reparative tissue on the articular surface and to analyse the properties of the reparative tissue after hemicallotasis osteotomy (HCO) using MRI T1ρ and T2 mapping. METHODS: Coronal T1ρ and T2 mapping and three-dimensional gradient-echo images were obtained from 20 subjects with medial knee osteoarthritis. We set the regions of interest (ROIs) on the full-thickness cartilage of the medial femoral condyle (MFC) and medial tibial plateau (MTP) of the knee and measured the cartilage thickness (mm) and T1ρ and T2 relaxation times (ms). Statistical analysis of time-dependent changes in the cartilage thickness and the T1ρ and T2 relaxation times was performed using one-way analysis of variance, and Scheffe's test was employed for post hoc multiple comparison. RESULTS: The cartilage-like repair tissue appeared on the cartilage surface of the medial compartment post-operatively, and the cartilage thickness showed a significant increase between the pre-operative and one-year post-operative time points (MFC; p = 0.003, MTP; p < 0.001). The T1ρ values of the cartilage-like repair tissue showed no difference over time, however, the T2 values showed a significant decrease between the pre-operative and one-year post-operative time points (MFC; p = 0.004, MTP; p = 0.040). CONCLUSION: This study clarified that the fibrocartilage-like repair tissue appeared on the articular surface of the medial compartment after HCO as evidenced by MRI T1ρ and T2 mapping.Cite this article: H. Nishioka, E. Nakamura, J. Hirose, N. Okamoto, S. Yamabe, H. Mizuta. MRI T1ρ and T2 mapping for the assessment of articular cartilage changes in patients with medial knee osteoarthritis after hemicallotasis osteotomy. Bone Joint Res 2016;5:294-300. DOI: 10.1302/2046-3758.57.BJR-2016-0057.R1.

The structured diagnostic interview for sleep patterns and disorders: rationale and initial evaluation.

OBJECTIVES: We aimed to describe and report the initial validity of a newly developed structured interview for sleep disorders (Diagnostic Interview for Sleep Patterns and Disorders [DISP]) administered by trained lay interviewers. METHODS: A total of 225 patients with various sleep disorders were recruited from two nationally recognized sleep centers in the United States. The International Classification of Sleep Disorders, second edition (ICSD-2) criteria, were used to classify sleep disorders (e.g., delayed sleep phase disorder, hypersomnia, narcolepsy with cataplexy [NC], restless legs syndrome [RLS], periodic limb movement disorder [PLMD], insomnia, rapid eye movement sleep behavior disorder [RBD], and obstructive sleep apnea [OSA]). Interview diagnoses were compared with final diagnoses by sleep specialists (reference diagnosis based on clinical history, examination, and polysomnography [PSG] when indicated). RESULTS: DISP diagnoses had fair to substantial concordance with clinician diagnoses for various sleep disorders, with area under the receiver operator characteristic curves (AUC) ranging from 0.65 to 0.84. Participants classified by the clinician as having a sleep disorder were moderately well-detected (sensitivity ranging from 0.50 for RBD disorder to 0.87 for insomnia). Substantial specificity (>0.8) also was seen for five of the eight sleep disorders (i.e., delayed sleep phase, hypersomnia, NC, PLMD, and RBD). Interviews were more likely than clinicians to detect disorders secondary to the primary sleep problem. CONCLUSIONS: The DISP provides an important tool for the detection of a wide range of sleep disorders in clinical settings and is particularly valuable in the detection of secondary disorders that were not the primary referral diagnosis.

The long-term outcome of open-wedge osteotomy of the proximal tibia with hemicallotasis.

We report the long-term outcome of 33 patients (37 knees) who underwent proximal tibial open-wedge osteotomy with hemicallotasis (HCO) for medial osteoarthritis of the knee between 1995 and 2000. Among these, 29 patients with unilateral HCO were enrolled and 19 were available for review at a mean of 14.2 years (10 to 15.7) post-operatively. For these 19 patients, the mean Hospital for Special Surgery knee score was 60 (57 to 62) pre-operatively and 85 (82 to 87) at final follow-up (p < 0.001; paired t-test). The femorotibial angle and tibial inclination angle (IA) were measured at short-term follow-up, one to four years post-operatively, and showed no significant subsequent changes. The clinical scores and radiological measurements showed little change over time. One patient required conversion to total knee replacement during this time. These results suggest that the coronal angle achieved at operation is maintained at long-term follow up after HCO without alteration of the IA, providing a good long-term clinical outcome.

Independence of familial transmission of mania and depression: results of the NIMH family study of affective spectrum disorders.

The goal of this study is to investigate the familial transmission of the spectrum of bipolar disorder in a nonclinical sample of probands with a broad range of manifestations of mood disorders. The sample included a total of 447 probands recruited from a clinically enriched community screening and their 2082 adult living and deceased first-degree relatives. A best estimate diagnostic procedure that was based on either direct semistructured interview or structured family history information from multiple informants regarding non-interviewed relatives was employed. Results revealed that there was specificity of familial aggregation of bipolar I (BP I; odds ratio (OR)=8.40; 3.27-20.97; h2=0.83) and major depressive disorder (OR=2.26; 1.58-3.22; h2=0.20), but not BP II. The familial aggregation of BP I was primarily attributable to the familial specificity of manic episodes after adjusting for both proband and relative comorbid anxiety and substance use disorders. There was no significant cross-aggregation between mood disorder subtypes suggesting that the familial transmission of manic and major depressive episodes is independent despite the high magnitude of comorbidity between these mood states. These findings confirm those of earlier studies of the familial aggregation of bipolar disorder and major depression in the first nonclinical sample, and the largest family study of bipolar disorder in the USA using contemporary nonhierarchical diagnostic criteria for mood and anxiety disorders. The results suggest that these major components of bipolar disorder may represent distinct underlying pathways rather than increasingly severe manifestations of a common underlying diathesis. Therefore, dissection of the broad bipolar phenotype in genetic studies could actually generate new findings that could index novel biologic pathways underlying bipolar disorder.

Downregulation of Ral GTPase-activating protein promotes tumor invasion and metastasis of bladder cancer.

The small GTPase Ral is known to be highly activated in several human cancers, such as bladder, colon and pancreas cancers. It is reported that activated Ral is involved in cell proliferation, migration and metastasis of bladder cancer. This protein is activated by Ral guanine nucleotide exchange factors (RalGEFs) and inactivated by Ral GTPase-activating proteins (RalGAPs), the latter of which consist of heterodimers containing a catalytic α1 or α2 subunit and a common ß subunit. In Ras-driven cancers, such as pancreas and colon cancers, constitutively active Ras mutant activates Ral through interaction with RalGEFs, which contain the Ras association domain. However, little is known with regard to the mechanism that governs aberrant activation of Ral in bladder cancer, in which Ras mutations are relatively infrequent. Here, we show that Ral was highly activated in invasive bladder cancer cells due to reduced expression of RalGAPα2, the dominant catalytic subunit in bladder, rather than increased expression of RalGEFs. Exogenous expression of wild-type RalGAPα2 in KU7 bladder cancer cells with invasive phenotype, but not mutant RalGAPα2-N1742K lacking RalGAP activity, resulted in attenuated cell migration in vitro and lung metastasis in vivo. Furthermore, genetic ablation of Ralgapa2 promoted tumor invasion in a chemically-induced murine bladder cancer model. Importantly, immunohistochemical analysis of human bladder cancer specimens revealed that lower expression of RalGAPα2 was associated with advanced clinical stage and poor survival of patients. Collectively, these results are highly indicative that attenuated expression of RalGAPα2 leads to disease progression of bladder cancer through enhancement of Ral activity.

JunB promotes cell invasion and angiogenesis in VHL-defective renal cell carcinoma.

Inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene causes both hereditary and sporadic clear-cell renal-cell carcinoma (ccRCC). Although the best-characterized function of the VHL protein (pVHL) is regulation of hypoxia-inducible factor-α (HIFα), pVHL also controls the development of pheochromocytoma through HIF-independent pathways by regulating JunB. However, it is largely unknown how these pathways contribute to the development and progression of ccRCC. In the present study, we confirmed that JunB was upregulated in VHL-defective ccRCC specimens by immunostaining. Short-hairpin RNA (shRNA)-mediated knockdown of JunB in 786-O and A498 VHL null ccRCC cells suppressed their invasiveness. In addition, JunB knockdown significantly repressed tumor growth and microvessel density in xenograft tumor assays. Conversely, forced expression of wild-type, but not dimerization-defective, JunB in a VHL-restored 786-O subclone promoted invasion in vitro and tumor growth and vessel formation in vivo. Quantitative PCR array analysis revealed that JunB regulated multiple genes relating to tumor invasion and angiogenesis such as matrix metalloproteinase-2 (MMP-2), MMP-9 and chemokine (C-C motif) ligand-2 (CCL2) in 786-O cells. JunB knockdown in these cells reduced the proteolytic activity of both MMPs in gelatin zymography and the amount of CCL2 in the culture supernatant. Moreover, shRNA-mediated knockdown of MMP-2 or inhibition of CCL2 activity with a neutralizing antibody repressed xenograft tumor growth and angiogenesis. Collectively, these results suggest that JunB promotes tumor invasiveness and enhances angiogenesis in VHL-defective ccRCCs.

Dioxins in ascites and serum of women with endometriosis: a pilot study.

BACKGROUND: Animal studies and laboratory experiments have demonstrated that exposure to dioxins may be involved in the pathophysiology of endometriosis. However, recent epidemiological investigations have shown conflicting results. Although peritoneal fluid is a specific microenvironment playing a pivotal role in the development of endometriosis, to our knowledge, there is no published study evaluating the concentrations of dioxins in serum and peritoneal fluid simultaneously. The present study explores the possible correlation between the local peritoneal fluid levels of dioxins and concurrent endometriosis. METHODS: There were 17 infertile women enrolled in the present study. After the diagnostic laparoscopic examination, the women were divided into two groups: endometriosis (n = 10) and controls (n = 7). We measured 29 dioxins simultaneously in serum and peritoneal fluid samples: 7 polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), and 12 polychlorinated biphenyls (dioxin-like PCBs). A dioxin toxic equivalency (TEQ) system was utilized to calculate the dioxin concentration in each sample. RESULTS: Serum concentrations of itemized components of 29 dioxins were similar in the endometriosis patients compared with the controls. Higher concentrations of PCDFs and dioxin-like PCBs were observed in peritoneal fluid than in serum, whereas the reverse was shown for PCDDs. Statistical analysis showed that higher levels of dioxin TEQ (PCDDs and PCDFs) in peritoneal fluid were significantly associated with an increased risk of endometriosis (OR: 2.5; 95% CI: 1.17-5.34; P = 0.035). CONCLUSIONS: This is the first report suggesting that higher concentrations of dioxins (PCDDs and PCDFs) in peritoneal fluid are linked to endometriosis. More detail and epidemiological research is warranted to further explore this link.

Inframalleolar bypass grafts for limb salvage.

OBJECTIVE: To report our experience of long-term results of inframalleolar bypass. DESIGN: Retrospective analysis. MATERIALS AND METHODS: We analysed 122 inframalleolar bypasses performed between January 1991 and June 2005 in 116 patients. Most patients were treated for critical ischaemia (97%). The indication for the use of podalic arteries was a lack of tibial arteries with run-off to the foot. The dorsalis pedis was predominantly used for distal anastomoses (62.3%) and the greater saphenous vein (84.4%) as the conduit. The follow-up periods ranged from 1 to 60 months. The endpoints analysed were graft patency, limb salvage, preservation of deambulation and survival rate. RESULTS: The cumulative patency was 58.2% at 3 years and 53.4% at 5 years. The best results were achieved with the devalvulated greater saphenous veins. Limb salvage was 70.0% at 3 years and 50.4% at 5 years, with preserved deambulation rates of 57.3% and 47.1%, respectively. There were 36 major and 45 minor amputations. At 3 years, the survival rate was 50.2% and the surgical mortality 13%. Female sex was associated with worse results for cumulative patency and limb salvage (P<0.01). CONCLUSIONS: In the long term, inframalleolar bypass is a satisfactory option for limb salvage.

[Giant left atrial myxoma with ossification on having a fever; report of a case].

A 37-year-old female with a fever had a medical examination, and was pointed out cardiac murmur. She was referred to our hospital for a further examination. Blood cultures were positive for Streptococcus milleri group. Thoracic echocardiogram demonstrated a giant left atrial tumor, arising from the portion of the interatrial septum, and mitral insufficiency. We removed the tumor completely and performed mitral annuloplasty. The tumor was diagnosed as myxoma with ossification by histopathological examination. She discharged from our hospital 25 days after the operation without complication and does not recur for 3 years. We consider our case as extremely rare, because it revealed giant left atrial myxoma with ossification and mitral insufficiency at the same time.

[Thoracoabdominal aorta replacement for penetrating atherosclerotic ulcers of suprarenal abdominal aorta].

A 58-year-old man with a complaint of a feeling of fullness and constipation was admitted to our hospital. Enhanced computed tomography (CT) images demonstrated sacral aneurysm with multiple penetrating atherosclerotic ulcer (PAU) at the abdominal aorta above the renal artery. The aneurysm was expanded for 2 weeks progressively. An urgent thracoabdominal aorta replacement was performed. Pathological findings showed that the media of aorta was destroyed and dissected, and intramural hematoma was found. The postoperative course was good. He has been from any aortic events 12 months after surgery.

Comparative evaluation of absorption, distribution, and excretion of YM758, a novel If channel inhibitor, between albino and non-albino rats.

1. YM758 is a novel If channel inhibitor for the treatment of stable angina and atrial fibrillation. The absorption, distribution, and excretion of YM758 have been investigated in albino and non-albino rats after a single oral administration of (14)C-YM758 monophosphate. 2. YM758 was well absorbed from all segments of the gastrointestinal tract except for the stomach. After oral administration, the ratio of AUC(0-1 h) between the plasma concentrations of radioactivity and the unchanged drug was estimated to be 17.7%, which suggests metabolism. 3. The distribution of the radioactivity derived from (14)C-YM758 in tissues was evaluated both in albino and non-albino rats. The radioactivity concentrations in most tissues were higher than those in plasma, which indicates that the radioactivity is well distributed to tissues. Extensive accumulation and slower elimination of radioactivity were noted in the thoracic aorta of albino and non-albino rats as well as in the eyeballs of non-albino rats. The recovery rates of radioactivity in urine and bile after oral dosing to bile duct-cannulated albino rats were 17.8% and 57.3%, respectively. 4. These results suggest that YM758 was extensively absorbed, subjected to metabolism, and excreted mainly into the bile after oral administration to rats, and extensive accumulation of the unchanged drug and/or metabolites into tissues such as the thoracic aorta and eyeballs was observed.

The chondrogenic repair response of undifferentiated mesenchymal cells in rat full-thickness articular cartilage defects.

OBJECTIVE: The aim of this study is to develop a rat model of full-thickness articular cartilage defects that is suitable for detailed molecular analyses of the regenerative repair of cartilage. MATERIALS AND METHODS: The V-shaped full-thickness defects (width: 0.7 mm; depth: 0.8 mm; and length: 4mm) were created in the femoral patellar groove of 6 weeks old male rats using a custom-built twin-blade device. Prior to starting the repair experiments, our device was examined for its accuracy and reliability in generating defects. Then, the time course of the repair response in these cartilage defects was examined using a semi-quantitative histological grading scale. The expression of chondrogenic differentiation markers in the reparative regions was examined with immunohistochemistry and in situ hybridization. RESULTS: Our device creates full-thickness articular cartilage defects uniformly. In these defects, undifferentiated mesenchymal cells filled the defect cavities (4 days) and initiated chondrogenic differentiation at the center of the defect (7 days). Cartilage formation was observed in the same region (2 weeks). Finally, hyaline-like articular cartilage and subchondral bone layers were reconstituted in their appropriate locations (4 weeks). CONCLUSIONS: We have successfully developed a rat model containing identically sized full-thickness defects of articular cartilage that can undergo chondrogenic repair in a reproducible fashion.