First-passage process in degree space for the time-dependent Erdos-Rényi and Watts-Strogatz models.

In this work, we investigate the temporal evolution of the degree of a given vertex in a network by mapping the dynamics into a random walk problem in degree space. We analyze when the degree approximates a preestablished value through a parallel with the first-passage problem of random walks. The method is illustrated on the time-dependent versions of the Erdos-Rényi and Watts-Strogatz models, which were originally formulated as static networks. We have succeeded in obtaining an analytic form for the first and the second moments of the first-passage time and showing how they depend on the size of the network. The dominant contribution for large networks with N vertices indicates that these quantities scale on the ratio N/p, where p is the linking probability.

Efficacy of dimethyl fumarate in Japanese multiple sclerosis patients: interim analysis of randomized, double-blind APEX study and its open-label extension.

BACKGROUND: Current data for the use of dimethyl fumarate (DMF) in Japanese patients with relapsing-remitting multiple sclerosis (RRMS) is limited. OBJECTIVES: To assess the efficacy of DMF in Japanese patients with RRMS. METHODS: The phase 3, multinational APEX study (ClinicalTrials.gov identifier: NCT01838668) consisted of two parts: a 24-week double-blind part where subjects were randomized to receive DMF 240 mg or placebo twice daily in East Asian and Eastern European countries, and an open-label extension part where all subjects received DMF. The primary endpoint was the total number of new gadolinium-enhancing lesions in Weeks 12-24. In this interim analysis, we report efficacy data in the Japanese subgroup (DMF n = 56; placebo n = 58) over 72 weeks, including an extension phase. RESULTS: DMF reduced the total number of new gadolinium-enhancing lesions in Weeks 12-24 by 85% versus placebo (p < 0.0001). At Week 24, the annualized relapse rate was also reduced by 48% with DMF, versus placebo. DMF reduced the probability of relapse from Week 8 and was sustained. The number of gadolinium-enhancing lesions was maintained through 72 weeks. CONCLUSIONS: DMF demonstrated sustained efficacy in this Japanese subgroup. The results were consistent with those observed in studies of DMF enrolling primarily Caucasian patients.

Carotid artery disease in post-stroke survivors and effects of enriched environment on stroke pathology in a mouse model of carotid artery stenosis.

AIMS: Carotid artery disease (CAD) is an important risk factor for stroke. We first evaluated CAD and stroke pathology in elderly post-stroke survivors. To simulate CAD, we assessed long-term consequences of bilateral common carotid artery stenosis (BCAS) in mice and exposed them to environmental enrichment (EE). METHODS: Histopathological methods were used to determine degrees of CAD (% area stenosis), brain infarct types, sizes and distribution in post-stroke survivors and BCAS mice. Adult male C57BL/6J mice after BCAS or sham surgery were randomly assigned to standard housing (Std) or limited (3 h) or full-time (Full) exposure to EE per day for 12 weeks. RESULTS: High frequencies of moderate carotid artery stenosis (51-75%) were evident in post-stroke survivors whereas those with severe CAD (>75% stenosis) exhibited greater numbers of cortical rather than subcortical infarcts and, were at higher risk of developing dementia. BCAS in mice reduced cerebral blood flow by 52% (P < 0.01) and thickened carotid artery walls, regardless of EE duration. Remarkably, the total and cortical infarcts declined by >50% in BCAS mice exposed to EE compared with BCAS-Std (P < 0.01). Frontal lobe and cortical strokes were associated with worsening working memory tested in a radial maze paradigm. Proteomic analysis revealed EE, both BCAS-3 h and BCAS-Full attenuated coagulation cascade factors including fibrinogen and von Willebrand factor, markers of blood-brain barrier damage. CONCLUSION: Small cortical and subcortical infarcts were evident in both post-stroke survivors with CAD and BCAS mice. Experimental evidence suggested that moderate exposure to EE is sufficient to reduce subsequent stroke lesions.

Random walk in degree space and the time-dependent Watts-Strogatz model.

In this work, we propose a scheme that provides an analytical estimate for the time-dependent degree distribution of some networks. This scheme maps the problem into a random walk in degree space, and then we choose the paths that are responsible for the dominant contributions. The method is illustrated on the dynamical versions of the Erdos-Rényi and Watts-Strogatz graphs, which were introduced as static models in the original formulation. We have succeeded in obtaining an analytical form for the dynamics Watts-Strogatz model, which is asymptotically exact for some regimes.

Aging and fluctuation-dissipation ratio in a nonequilibrium q-state lattice model.

A generalized version of the nonequilibrium linear Glauber model with q states in d dimensions is introduced and analyzed. The model is fully symmetric, its dynamics being invariant under all permutations of the q states. Exact expressions for the two-time autocorrelation and response functions on a d-dimensional lattice are obtained. In the stationary regime, the fluctuation-dissipation theorem holds, while in the transient the aging is observed with the fluctuation-dissipation ratio leading to the value predicted for the linear Glauber model.

Manipulation of cell-sized phospholipid-coated microdroplets and their use as biochemical microreactors.

Cell-sized water droplets coated by a phospholipid layer mimicking the inner surface of living cells were manipulated by laser tweezers and used as biochemical microreactors. The cell-sized phospholipid-coated microdroplets (CPMDs) consisted of a water droplet in mineral oil with a diameter of 1-100 microm and coated by 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine. We monitored the time development of biochemical reactions in a single CPMD obtained after the controlled fusion of two CPMDs containing a substrate and an enzyme, respectively. We present results on two enzymatic reactions: calcein production in the presence of esterase and green fluorescence protein expression.

Fluctuation-dissipation theorem and the linear Glauber model.

We obtain exact expressions for the two-time autocorrelation and response functions of the -dimensional linear Glauber model. Although this linear model does not obey detailed balance in dimensions d > or = 2, we show that the usual form of the fluctuation-dissipation ratio still holds in the stationary regime. In the transient regime, we show the occurrence of aging, with a special limit of the fluctuation-dissipation ratio, x(infinity) = 1/2, for a quench at the critical point.

Lower haemoglobin level and subsequent decline in kidney function in type 2 diabetic adults without clinical albuminuria.

AIMS/HYPOTHESIS: Anaemia has been suggested to be an independent risk factor for subsequent progression of advanced diabetic nephropathy; however, the relationship between haemoglobin levels and progression of nephropathy in patients without clinical albuminuria is unknown. METHODS: We conducted this prospective hospital-based cohort study of 464 type 2 diabetic patients (149 women and 315 men, 55+/-13 [mean+/-SD] years of age) with serum creatinine <177 micromol/l (2.00 mg/dl) and urinary albumin : creatinine ratio <300 mg/g creatinine. GFR was estimated using the equation formulated by the Modification of Diet in Renal Disease Study group, refitted for Japanese individuals. Most patients had haemoglobin concentrations in the normal range (144+/-15 g/l), only modest renal impairment (GFR: 74.8+/-14.5 ml min(-1) 1.73 m(-2)), and normal urinary albumin levels (81.5/18.5% with normo-/microalbuminuria). The primary outcome measurement was the rate of change in GFR determined by regression analysis with GFR as a function of time. Patients were followed up for a mean observation period of 5.0+/-0.9 (range: 2.5 to 6.2) years. RESULTS: Univariate and multiple regression analyses yielded a significant association between the rate of change in GFR and baseline haemoglobin concentration. After adjusting for covariates, the rate of decline in GFR was significantly greater in patients in the lowest haemoglobin quartile (-3.27 ml min(-1) 1.73 m(-2) year(-1)) than in the third (-2.71 ml min(-1) 1.73 m(-2) year(-1), p = 0.024) and highest quartiles (-2.78 ml min(-1) 1.73 m(-2) year(-1), p = 0.046). CONCLUSIONS/INTERPRETATION: Lower haemoglobin concentrations in type 2 diabetic patients without clinical albuminuria may be a significant predictor of subsequent decline in GFR.

Structural transition of actin filament in a cell-sized water droplet with a phospholipid membrane.

Actin filament, F-actin, is a semiflexible polymer with a negative charge, and is one of the main constituents of cell membranes. To clarify the effect of cross talk between a phospholipid membrane and actin filaments in cells, we conducted microscopic observations on the structural changes in actin filaments in a cell-sized (several tens of micrometers in diameter) water droplet coated with a phospholipid membrane such as phosphatidylserine (PS; negatively charged head group) or phosphatidylethanolamine (PE; neutral head group) as a simple model of a living cell membrane. With PS, actin filaments are distributed uniformly in the water phase without adsorption onto the membrane surface between 2 and 6 mM Mg2+, while between 6 and 12 mM Mg2+, actin filaments are adsorbed onto the inner membrane surface. With PE, the actin filaments are uniformly adsorbed onto the inner membrane surface between 2 and 12 mM Mg2+. With both PS and PE membranes, at Mg2+ concentrations higher than 12 mM, thick bundles are formed in the bulk water droplet accompanied by the dissolution of actin filaments from the membrane surface. The attraction between actin filaments and membrane is attributable to an increase in the translational entropy of counterions accompanied by the adsorption of actin filaments onto the membrane surface. These results suggest that a microscopic water droplet coated with phospholipid can serve as an easy-to-handle model of cell membranes.

Severe paradoxical intracranial embolism and pulmonary emboli during hip hemiarthroplasty.

Both paradoxical intracranial embolism, an intracranial arterial embolism caused by venous embolic material that has passed through a right-to-left shunt, and pulmonary arterial embolism are life-threatening complications of joint arthroplasty. We report a case of severe paradoxical intracranial embolism and pulmonary embolism that occurred during hip hemiarthroplasty.

Adhesions in the temporomandibular joint: formation and significance.

BACKGROUND: Adhesions are frequently seen in the deranged temporomandibular joint (TMJ). In the early stage of the degenerative process the adhesion does not seem to be a significant factor in reduced mandibular movement. This is reversed in advanced degenerative joint disease where the adhesion requires release to achieve a satisfactory clinical result. Correlation of clinical history and findings within the joint should increase understanding of limited jaw movement. METHODS: Arthroscopic examination of deranged TMJs was performed on 75 patients with limited jaw opening and correlated with the history of the derangement. RESULTS: A progressive maturation of adhesion formation was observed with longer standing symptoms. A different adhesion pattern was noted with derangement caused by direct trauma on the joint. CONCLUSIONS: Internal derangement of the TMJ is associated with formation of intra-articular adhesions. These are unlikely to be associated with reduced condyle movement in the early phase of the derangement. Later stage adhesions are more substantial and require release to achieve a satisfactory clinical outcome.

Amino acid substitutions of coiled-coil protein Tpr abrogate anchorage to the nuclear pore complex but not parallel, in-register homodimerization.

Tpr is a protein component of nuclear pore complex (NPC)-attached intranuclear filaments. Secondary structure predictions suggest a bipartite structure, with a large N-terminal domain dominated by heptad repeats (HRs) typical for coiled-coil--forming proteins. Proposed functions for Tpr have included roles as a homo- or heteropolymeric architectural element of the nuclear interior. To gain insight into Tpr's ultrastructural properties, we have studied recombinant Tpr segments by circular dichroism spectroscopy, chemical cross-linking, and rotary shadowing electron microscopy. We show that polypeptides of the N-terminal domain homodimerize in vitro and represent alpha-helical molecules of extended rod-like shape. With the use of a yeast two-hybrid approach, arrangement of the coiled-coil is found to be in parallel and in register. To clarify whether Tpr can self-assemble further into homopolymeric filaments, the full-length protein and deletion mutants were overexpressed in human cells and then analyzed by confocal immunofluorescence microscopy, cell fractionation, and immuno-electron microscopy. Surplus Tpr, which does not bind to the NPC, remains in a soluble state of approximately 7.5 S and occasionally forms aggregates of entangled molecules but neither self-assembles into extended linear filaments nor stably binds to other intranuclear structures. Binding to the NPC is shown to depend on the integrity of individual HRs; amino acid substitutions within these HRs abrogate NPC binding and render the protein soluble but do not abolish Tpr's general ability to homodimerize. Possible contributions of Tpr to the structural organization of the nuclear periphery in somatic cells are discussed.

Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial Infarction Investigations in Japan.

OBJECTIVES: To determine the clinical features of a novel heart syndrome with transient left ventricular (LV) apical ballooning, but without coronary artery stenosis, that mimics acute myocardial infarction, we performed a multicenter retrospective enrollment study. BACKGROUND: Only several case presentations have been reported with regard to this syndrome. METHODS: We analyzed 88 patients (12 men and 76 women), aged 67 +/- 13 years, who fulfilled the following criteria: 1) transient LV apical ballooning, 2) no significant angiographic stenosis, and 3) no known cardiomyopathies. RESULTS: Thirt-eight (43%) patients had preceding aggravation of underlying disorders (cerebrovascular accident [n = 3], epilepsy [n = 3], exacerbated bronchial asthma [n = 3], acute abdomen [n = 7]) and noncardiac surgery or medical procedure (n = 11) at the onset. Twenty-four (27%) patients had emotional and physical problems (sudden accident [n = 2], death/funeral of a family member [n = 7], inexperience with exercise [n = 6], quarreling or excessive alcohol consumption [n = 5] and vigorous excitation [n = 4]). Chest symptoms (67%), electrocardiographic changes (ST elevation [90%], Q-wave formation [27%] and T-wave inversion [97%]) and elevated creatine kinase (56%) were found. After treatment of pulmonary edema (22%), cardiogenic shock (15%) and ventricular tachycardia/fibrillation (9%), 85 patients had class I New York Heart Association function on discharge. The LV ejection fraction improved from 41 +/- 11% to 64 +/- 10%. Transient intraventricular pressure gradient and provocative vasospasm were documented in 13/72 (18%) and 10/48 (21%) of the patients, respectively. During follow-up for 13 +/- 14 months, two patients showed recurrence, and one died suddenly. CONCLUSIONS: A novel cardiomyopathy with transient apical ballooning was reported. Emotional or physical stress might play a key role in this cardiomyopathy, but the precise etiologic basis still remains unclear.

Does primary stenting preserve cardiac function in myocardial infarction? A case-control study. NORTH-981 investigators. Network of revascularisation therapy in Hokkaido.

OBJECTIVE: To investigate whether coronary stenting limits myocardial injury and preserves left ventricular function. DESIGN AND SETTING: Prospective multicentre case-control study of primary percutaneous transluminal coronary angioplasty (PTCA) with and without stenting, performed in seven cardiovascular centres. SUBJECTS AND METHODS: 45 consecutive patients with acute myocardial infarction who were treated with successful primary stenting (Stent group) and did not have restenosis were paired with 45 matched control subjects with acute myocardial infarction treated by successful primary PTCA without stenting, also with no restenosis (POBA group). RESULTS: In comparison with the POBA group, the Stent group-especially those patients with a left anterior descending coronary artery lesion-had a smaller hypokinesis area (mean (SD): 15. 1 (20.0) v 34.4 (24.3) chords), reduced hypokinesis area/risk area (25.2 (31.9)% v 58.8 (40.1)%), and a larger ejection fraction (63.3 (10.2)% v 51.7 (11.7)%) evaluated by quantitative left ventriculography using the centerline method. In the Stent group, the correlation between risk area and hypokinesis area was significantly shifted downward. Multiple logistic regression analysis on infarct size limitation (hypokinesis area/risk area < 50%) identified preinfarction angina in all subjects and preinfarction angina and stenting in patients with left anterior descending coronary artery lesions as explanatory factors. CONCLUSIONS: Primary PTCA using a coronary stent is effective in preventing myocardial injury and restoring left ventricular function in patients with anterior acute myocardial infarction.

Intrauterine and intravaginal insemination with frozen canine semen using an extender consisting of orvus ES paste-supplemented egg yolk tris-fructose citrate.

Our previous report indicated that addition of Orvus ES Paste (OEP) to the extender of frozen canine semen protected acrosomes and maintained sperm motility after thawing. In this study, artificial insemination (AI) using the frozen semen was carried out. The frozen semen was prepared using egg yolk Tris-fructose citrate, and the final concentrations of glycerol and OEP were 7% (v/v) and 0.75% (v/v), respectively. AI was performed during the optimal mating period predicted from the peripheral plasma progesterone level. In intrauterine insemination (IUI), the bitches were laparotomized and 1 x 10(8) spermatozoa were infused into one of the uterine horns. In insemination of non-OEP supplemented semen, 3 x 10(8) spermatozoa were inseminated. In intravaginal insemination (IVI), 10-40 x 10(8) spermatozoa were inseminated. Conception was obtained in nine of 10 bitches (90.0%) that underwent IUI. The number of newborns was from 1 to 7 (mean 3.6 +/- 0.9). The mean ratio of the number of puppies to the number of ovulations in the inseminated uterine horn was 71.8%. The number of puppies did not exceed the number of ovulation in the inseminated uterine horn. Conception using non-OEP supplemented frozen semen was unsuccessful in all four bitches. In IVI, conception was not obtained in any of the six bitches that received insemination of 10 x 10(8) or 40 x 10(8) spermatozoa, but two of three bitches that received insemination of 20 x 10(8) spermatozoa were fertilized. It was shown that a high conception rate can be obtained by IUI using OEP-supplemented frozen canine semen. Developmenmt of a non-surgical method of IUI and a method of freezing canine sperm applicable to IVI is necessary.

Cystic hamartoma of the renal pelvis: imaging features.

We report a case of a 50-year-old woman with histologically proven cystic hamartoma of the renal pelvis, focusing on the imaging findings and pathologic features. A large multicystic tumor with solid components in the left kidney was enhanced on both contrast-enhanced CT and gadolinium-enhanced MR images. Angiographic images showed irregular tumor vessels with moderate tumor stain.

Effects of orvus ES paste on canine spermatozoal longevity after freezing and thawing.

Because of weak resistance of canine sperm to freezing, an applicable method of preparing canine frozen semen has not yet been established. We added various concentrations of Orvus ES Paste (OEP) to egg yolk Tris-fructose citrate, and investigated its effectiveness on survival of spermatozoa. Addition of 0.5-1.0% OEP to the extender for freezing canine semen was effective in prolonging post-thaw survival of spermatozoa.

Effect of addition of Orvus ES paste to frozen canine semen extender on sperm acrosomes.

Using the triple-stain technique, we investigated whether sperm acrosomes in frozen canine semen were protected during freezing and thawing by addition of a surfactant, Orvus ES Paste (OEP), to the extender. Acrosomes were clearly shown to be protected by the addition of OEP to the entender when compared with those in sperm frozen without OEP addition (p<0.05).