Glycaemic management in a child with ornithine transcarbamylase deficiency undergoing cardiac surgery with hypothermic cardiopulmonary bypass.

There is a lack of evidence regarding the optimal intra-operative glycaemic level of patients with ornithine transcarbamylase deficiency to prevent cerebral oedema due to protein catabolism and hyperammonemia. We describe a case of a two-year-old girl with ornithine transcarbamylase deficiency who underwent cardiac surgery requiring cardiopulmonary bypass. A high-dose dextrose infusion to prevent protein catabolism was given throughout surgery, which caused uncontrollable hyperglycaemia unresponsive to high-dose insulin administration. Factors contributing to the hyperglycaemia may have included surgical stress, steroid administration and hypothermia. During invasive surgery, anaesthetists should carefully adjust the rates of dextrose and insulin infusions, guided by close monitoring of blood ammonia, glucose and lactate.

Enhancement of the spin polarization of an Fe3O4(100) surface by nitric oxide adsorption.

The geometric, electronic and magnetic properties of a nitric oxide (NO) adsorbed Fe3O4(100) surface have been investigated using density functional theory (DFT) calculations. NO molecules preferentially bond with surface Fe(B) atoms via their N atoms. The generalized gradient approximation (GGA) is not recommended to be used in such a strongly correlated system since it provides not only an overestimation of the adsorption energy and an underestimation of the Fe(B)-N bond length, but also magnetic quenching of the adsorbate and the bonded Fe(B) atoms. In contrast, a tilted geometry and magnetization of the adsorbate and the bonded Fe(B) atom are obtained after including the strong on-site Coulomb interactions through a Hubbard term (GGA+U). The spin-down 2π* states of the NO molecule are filled and broadened due to the adsorbate-substrate interaction and the molecule-molecule interaction. The surface spin polarization close to the Fermi level is expected to be greatly enhanced by the NO adsorption which has significance for interface design in spintronic devices.

Reversible switching of the spin state in a manganese phthalocyanine molecule by atomic nitrogen.

Reversible control of the spin state of an organic molecule is significant for the development of molecular spintronic devices. Here, density functional theory calculations have been performed to study the adsorption of atomic nitrogen on a single manganese phthalocyanine (MnPc) molecule, three-layered MnPc, and MnPc on an Fe(100) surface. For all three cases, the N atom strongly adsorbs on top of the Mn atom and induces a significant variation of the geometric, electronic and magnetic properties. After N adsorption, an energy gap appears and the electronic states become unpolarized. Different functionals including three hybrid functionals are used in these calculations, and all yield a switchable spin state.

Half-metallicity induced by boron adsorption on an Fe3O4(100) surface.

The spin polarization of magnetite Fe3O4 is significantly reduced at its surfaces, which is unfavorable for the development of spintronic devices based on this material. In order to enhance the surface spin polarization, the Fe3O4(100) surface is modified here through the adsorption of boron (B) atoms and investigated using density functional theory (DFT) calculations. We find for the bulk-terminated and cation-redistributed surfaces that a band gap is opened in the spin-up electronic states due to the formation of a strong bond between the B atom and a surface oxygen atom, i.e., B adsorption induces half-metallicity at the Fe3O4(100) surface. Besides the surface Fe and O atoms, the adsorbed B atoms have a considerable density of -100% spin-polarized electronic states at the Fermi level, which might provide a means of improving the efficiency of spin injection into spintronic devices.

Predictors of delayed wound healing after endovascular therapy of isolated infrapopliteal lesions underlying critical limb ischemia in patients with high prevalence of diabetes mellitus and hemodialysis.

OBJECTIVES: Acceptable limb salvage rates underlie the widespread use of endovascular therapy (EVT) for patients with critical limb ischemia (CLI) secondary to isolated infrapopliteal lesions; however, post-EVT delayed wound healing remains a challenge. Predictors of delayed wound healing and their use in risk stratification of EVT in patients with CLI due to isolated infrapopliteal lesions are explored. METHODS: This was a retrospective multicenter study. 871 consecutive critically ischemic limbs were studied. There was tissue loss in 734 patients (age: 71 ± 10 years old; 71% male) who had undergone EVT between April 2004 and December 2012. The wound healing rate after EVT was estimated by the Kaplan-Meier method. The association between baseline characteristics and delayed wound healing was assessed by the Cox proportional hazard model. RESULTS: Diabetes mellitus and regular dialysis were present in 75% (553/734) and 64% (476/734) of patients, respectively; 67% of limbs (585/871) had Rutherford class 5 CLI; 8% (67/871) of wounds were located in the heel only; 25% (219/871) of limbs had Rutherford 6 (involving not only the heel); and 42% (354/871) of wounds were complicated by infection. The rate of freedom from major amputation at 1 year reached 88%, whereas the wound healing rate was 67%. Median time to wound healing was 146 days. By multivariate analysis, non-ambulatory status (hazard ratio [HR], 1.58; 95% confidence interval [CI] 1.31-1.91) serum albumin <3 g/dL (HR 1.42; 95% CI 1.08-1.86), Rutherford 6 (not only heel) (HR 1.68; 95% CI 1.33-2.14), wound infection (HR 1.24; 95% CI 1.03-1.50), EVT not based on angiosome concept (HR 1.28; 95% CI 1.06-1.55), and below the ankle (BTA) 0 vessel runoff after EVT (HR 1.45; 95% CI 1.14-1.86) were independent predictors of delayed wound healing. CONCLUSIONS: Non-ambulatory status, low albumin level, Rutherford 6 (not only heel), wound infection, indirect intervention, and poor BTA runoff were independent predictors for delayed wound healing after EVT in patients with CLI secondary to infrapopliteal lesions, and their use in risk stratification allows estimation of the wound healing rate.

Factors that predict in-hospital mortality in eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic small-vessel vasculitis associated with asthma, eosinophilia, and necrotizing vasculitis. EGPA is potentially life-threatening and often involves peripheral neuropathies, peptic ulcers, cerebral vessel disease, and cardiovascular disease. However, there is limited understanding of the prognostics factors for patients with EGPA. We investigated the clinical features and factors affecting patients' in-hospital mortality, using a national inpatient database in Japan. METHODS: We retrospectively collected data of EGPA patients who required hospitalization between July 2010 and March 2013, using the Diagnosis Procedure Combination database. We evaluated EGPA patients' characteristics and performed multivariate logistic regression analyses to assess the factors associated with in-hospital mortality. RESULTS: A total of 2195 EGPA patients were identified. The mean age was 61.9 years, 42.1% (924/2195) were male, and 41.6% (914/2195) had emergent admission. In-hospital deaths occurred in 97/2195 patients (4.4%). Higher in-hospital mortality was associated with age older than 65 years, disturbance of consciousness on admission, unscheduled admission, respiratory disease, cardio-cerebrovascular disease, renal disease, sepsis, and malignant disease on admission. Lower mortality was associated with female gender and peripheral neuropathies. CONCLUSIONS: Our study revealed the clinical features of EGPA patients who required hospitalization and the factors associated with their mortality. These results may be useful for physicians when assessing disease severity or treatments for hospitalized EGPA patients.

Complex relationship of body mass index with mortality in patients with critical limb ischemia undergoing endovascular treatment.

OBJECTIVE: To investigate the relationship between body mass index (BMI) and long-term outcomes of patients with CLI after endovascular treatment (EVT). DESIGN: Retrospective multicenter study. SUBJECTS: 1088 consecutive patients (1306 limbs, mean age 72 ± 10 years) with CLI who underwent EVT for isolated infrapopliteal artery lesions were evaluated. These subjects were identified in the J-BEAT III registry. METHODS: The patients were divided into groups based on BMI <18.5 kg/m2 (underweight, n = 188; 219 limbs), 18.5 to 24.9 kg/m2 (normal weight, n = 718; 868 limbs), and >25.0 kg/m2 (overweight/obese, n = 182; 219 limbs). The endpoints were overall survival and freedom from major adverse limb events (MALE). RESULTS: The median follow up period was 1.5 years (range: 1 month-8.7 years). The 3 year overall survival rates were 33.3%, 61.2%, and 69.8% in underweight, normal, and overweight/obese patients, respectively. The survival rate was significantly lower in underweight patients and significantly higher in overweight/obese patients compared with patients of normal weight (both p < .0001). The 3 year rates of freedom from MALE did not differ significantly among the three groups (36.4%, 45.4%, and 52.3%, respectively, p = .32). Age, BMI <18.5 kg/m2, heart failure, aortic valve stenosis, renal failure, triglyceride levels, serum albumin <3.0 g/dL, anticoagulant treatment, non-ambulatory status, and Rutherford 6 classification all were significantly associated with overall survival. CONCLUSIONS: BMI has a complex correlation with mortality in patients with CLI after EVT for isolated infrapopliteal artery lesions. Underweight patients with CLI have an extremely poor prognosis. Such patients have many other factors associated with mortality, but low BMI was identified as an independent predictor of a poor prognosis in patients with CLI. Similarly, normal weight patients had a small but significant increase in mortality compared with overweight/obese patients.

Increasing testicular temperature by exposure to elevated ambient temperatures restores spermatogenesis in adult Utp14b (jsd) mutant (jsd) mice.

Because mutations in the human UTP14C gene are associated with male infertility, we sought to develop a method for fertility restoration in azoospermic mice with a mutation in the orthologous Utp14b(jsd) (jsd) gene that have spermatogonial arrest. The method is based on our observation that elevation of testicular temperatures restores spermatogonial differentiation in jsd mutant mice. To non-surgically raise intrascrotal temperatures we placed these mice in incubators at different elevated ambient temperatures. Exposure of jsd/jsd mice to ambient temperatures of 34.5 °C or 35.5 °C for 24 days increased the proportion of tubules with spermatocytes from 0% in untreated controls to over 80%. As those higher temperatures interfere with spermatid differentiation, the mice were then transferred to incubators at 32-32.5 °C for the next 24 days. These environments allowed differentiation to progress, resulting in up to 42% of tubules having late spermatids and about half of the mutant mice having spermatozoa in testicular suspensions. When these spermatozoa were used in intracytoplasmic sperm injection, all gave rise to viable healthy offspring with normal weight gain and fertility. The successful restoration of fertility in Utp14b mutant mice suggests that transient testicular warming might also be useful for spermatogenesis recovery in infertile men with UTP14C gene mutations.

Ultrahigh vacuum and low-temperature cleaning of oxide surfaces using a low-concentration ozone beam.

We present a novel method of delivering a low-concentration (<15%) ozone beam to an ultra-high vacuum environment for the purpose of cleaning and dosing experimental samples through oxidation processing. The system described is safe, low-cost, and practical and overcomes the limitations of ozone transport in the molecular flow environment of high or ultrahigh vacuum whilst circumventing the use of pure ozone gas which is potentially highly explosive. The effectiveness of this method in removing surface contamination is demonstrated through comparison of high-temperature annealing of a simple oxide (MgO) in ozone and oxygen environments as monitored using quadrupole mass spectroscopy and Auger electron spectroscopy. Additionally, we demonstrate the potential of ozone for obtaining clean complex oxide surfaces without the need for high-temperature annealing which may significantly alter surface structure.

Magnetic moment enhancement and spin polarization switch of the manganese phthalocyanine molecule on an IrMn(100) surface.

The geometric, electronic, and magnetic structures of a manganese phthalocyanine (MnPc) molecule on an antiferromagnetic IrMn(100) surface are studied by density functional theory calculations. Two kinds of orientation of the adsorbed MnPc molecule are predicted to coexist due to molecular self-assembly on the surface-a top-site geometry with the Mn-N bonds aligned along the ⟨100⟩ direction, and a hollow-site orientation in which the Mn-N bonds are parallel to the ⟨110⟩ direction. The MnPc molecule is antiferromagnetically coupled to the substrate at the top site with a slight reduction in the magnetic moment of the Mn atom of the MnPc molecule (Mnmol). In contrast, the magnetic moment of the Mnmol is enhanced to 4.28 µB at the hollow site, a value larger than that in the free MnPc molecule (3.51 µB). Molecular distortion induced by adsorption is revealed to be responsible for the enhancement of the magnetic moment. Furthermore, the spin polarization of the Mnmol atom at around the Fermi level is found to change from negative to positive through an elongation of the Mn-N bonds of the MnPc. We propose that a reversible switch of the low/high magnetic moment and negative/positive spin polarization might be realized through some mechanical engineering methods.

Perioperative complications after aorto-iliac stenting: associated factors and impact on follow-up cardiovascular prognosis.

OBJECTIVES: To investigate factors associated with 30-day perioperative complications (POC) after aorto-iliac (AI) stenting, and to compare follow-up cardiovascular prognosis between patients with and without POC. MATERIALS AND METHODS: This was a retrospective multicenter study. We used a multicenter database of 2012 consecutive patients who successfully underwent AI stenting for peripheral arterial disease in 18 centers in Japan from January 2005 to December 2009 to analyze independent predictors of POC and impact of POC on prognosis by logistic regression and a Cox proportional hazard regression model, respectively. RESULTS: Mean age was 71 ± 9 years (median: 72 years; range: 37-98 years), and 1,636 patients (81%) were men. POC occurred in 126 patients (6.3%). In multivariate logistic regression analysis, old age (≥80 years), critical limb ischemia (CLI), and Trans Atlantic Inter-Societal Consensus (TASC) II class C/D were independently associated with POC with adjusted odds ratios and 95% confidence intervals (CI) of 1.9 (1.3-2.9), 2.3 (1.5-3.4), and 2.4 (1.6-3.4), respectively. Out of 2012 patients, 1995 were followed up for more than 30 days (mean: 2.6 ± 1.5 years; range: 2-2,393 days). In a Cox hazard regression model adjusted for baseline clinical characteristics, POC was positively and independently associated with follow-up major adverse cardiac events (adjusted hazard ratio [HR]: 1.9; 95% CI: 1.3-2.8; p = .002), but not with major adverse limb events and target lesion revascularization (adjusted HR: 1.4; 95% CI: 0.7-2.7; p = .25; and adjusted HR: 1.2; 95% CI 0.6-2.6; p = .568), respectively. CONCLUSIONS: Age >80 years, CLI, and TASC C/D lesion were positively associated with POC after AI stenting. Occurrence of POC appears to adversely affect follow-up cardiovascular, but not limb and vessel prognosis.

Significant variation of surface spin polarization through group IV atom (C, Si, Ge, Sn) adsorption on Fe3O4(100).

The adsorption of group IV atoms (C, Si, Ge, Sn) on the magnetite Fe3O4(100) surface is investigated by density functional theory calculations. All these atoms prefer to bond to the surface oxygen atom which has no tetrahedral Fe(A) neighbor. The spin-up surface states of clean Fe3O4(100) are completely removed and half-metallicity is recovered by C adsorption. The spin-up band gap of the C-adsorbed Fe3O4(100) surface is wider than that of the H-adsorbed one and closer to the value of bulk Fe3O4. For the adsorption of other group IV atoms, the adsorbate-substrate interaction decreases and the adsorbate-adsorbate interaction increases with the increase of atomic number Z. As a consequence, the spin polarization varies from -99.4% (C adsorption) to +44.2% (Sn adsorption) for the electronic states of the adsorbed atom integrated from -0.5 eV to the Fermi level. The ability to tune the surface spin polarization by the choice of adsorbate is of significance for magnetite-based spintronic devices.

Worse limb prognosis for indirect versus direct endovascular revascularization only in patients with critical limb ischemia complicated with wound infection and diabetes mellitus.

OBJECTIVES: To investigate factors in patients with critical limb ischemia (CLI) and isolated infrapopliteal lesions that adversely affect outcomes of endovascular therapy (EVT) with or without angiosome-oriented revascularization. METHODS: This was a retrospective multicenter study. We used a database of 718 consecutive CLI patients (70 ± 11 years, 75% diabetics, 68% on hemodialysis, 24% Rutherford class 6) with ischemic tissue loss due to isolated infrapopliteal lesions undergoing primary EVT. Primary outcome was MALE (major adverse limb event). Association between indirect EVT (recanalization of a non-angiosome-based artery) and outcome was assessed by Cox proportional hazard regression model. RESULTS: C-reactive protein (CRP) level was >3 mg/dL in 32% of cases. Indirect EVT (in 307 CLI patients, 43%), was associated with MALE (p = .04, hazard ratio [95% confidence interval] 1.25 [1.01, 1.55]), and interacted with CRP >3 mg/dL (p < .004) but not with other baseline characteristics. Indirect EVT with CRP >3 mg/dL had higher MALE risk (HR 2.08), and interacted with diabetes mellitus (DM) presence. Indirect EVT with CRP >3 mg/dL and DM had higher MALE risk (HR 2.17). CONCLUSION: Limb prognosis was equivalent for direct and indirect endovascular revascularization except in the presence of both diabetes and wound infection, when indirect revascularization has a poorer outcome.

Retinoic acids up-regulate functional eosinophil-driving receptor CCR3.

Eotaxins and their receptor CCR3 have a definitive role for tissue accumulation of eosinophils both under homeostatic and pathologic conditions. However, physiological stimuli that can up-regulate CCR3 in blood-derived human eosinophils have not been recognized. As a prior gene microarray study revealed up-regulation of CCR3 in eosinophils stimulated with retinoic acids (RAs), the expression of functional CCR3 was examined. We found that 9-cis RA and all-trans RA (ATRA) significantly induced surface CCR3 expression regardless of the presence of IL-3 or IL-5. Pharmacological manipulations with receptor-specific agonists and antagonists indicated that retinoic acid receptor-α activation is critical for CCR3 up-regulation. RA-induced CCR3 was associated with its functional capacity, in terms of the calcium mobilization and chemotactic response to eotaxin-1 (CCL11). Our study suggests an important role of vitamin A derivatives in the tissue accumulation of eosinophils.

Neurotransmitters, psychotropic drugs and microglia: clinical implications for psychiatry.

Psychiatric disorders have long and dominantly been regarded to be induced by disturbances of neuronal networks including synapses and neurotransmitters. Thus, the effects of psychotropic drugs such as antipsychotics and antidepressants have been understood to modulate synaptic regulation via receptors and transporters of neurotransmitters such as dopamine and serotonin. Recently, microglia, immunological/inflammatory cells in the brain, have been indicated to have positive links to psychiatric disorders. Positron emission tomography (PET) imaging and postmortem studies have revealed microglial activation in the brain of neuropsychiatric disorders such as schizophrenia, depression and autism. Animal models of neuropsychiatric disorders have revealed the underlying microglial pathologies. In addition, various psychotropic drugs have been suggested to have direct effects on microglia. Until now, the relationship between microglia, neurotransmitters and psychiatric disorders has not been well understood. Therefore, in this review, at first, we summarize recent findings of interaction between microglia and neurotransmitters such as dopamine, serotonin, norepinephrine, acetylcholine and glutamate. Next, we introduce up-to-date knowledge of the effects of psychotropic drugs such as antipsychotics, antidepressants and antiepileptics on microglial modulation. Finally, we propose the possibility that modulating microglia may be a key target in the treatment of various psychiatric disorders. Further investigations and clinical trials should be conducted to clarify this perspective, using animal in vivo studies and imaging studies with human subjects.

Epidemiological survey of the hoof wall cavity ('Gidoh' in Japanese) in racehorses.

In October 2001, a survey was conducted about cavities formed within the hoof wall (called GIDOH in Japanese) of racehorses at the Ritto and Miho Training Centres, which are managed by the Japan Racing Association (JRA). Gidoh is defined as a progressive cavity within the deep layers between the stratum medium and stratum internum. A total of 148 out of 5386 surveyed horses (2.75 per cent) were affected. Out of 244 affected feet, fore hooves (84.02 per cent) were more susceptible than hind hooves, and the site most affected was midline dead centre of the toe (59.62 per cent) which tends to place extra stress at the break-over point in a straight-line exercise. Logistic regression analysis revealed that prevalence was significantly related with horse affiliation (OR 0.65, 95 per cent CI 0.46 to 0.91) and age (OR 1.43 per one year, 95 per cent CI 1.27 to 1.61). We hypothesised that the primary cause of Gidoh development in JRA stables was mechanical deformation of the hoof wall during exercise, and secondary exciting causes can subsequently lead to the spread of the lesion over the entire hoof wall.

Anatomical predictors of major adverse limb events after infrapopliteal angioplasty for patients with critical limb ischaemia due to pure isolated infrapopliteal lesions.

OBJECTIVE: To identify anatomical factors associated with major adverse limb events (MALE) after angioplasty as the basis for a novel morphology-driven classification of infrapopliteal lesions. DESIGN: Retrospective-multicenter study. MATERIALS AND METHODS: Between March 2004 and October 2010, 1057 limbs from 884 patients with CLI due to isolated infrapopliteal lesions were studied. Freedom-from MALE, defined as major amputation or any reintervention, was assessed out to 2 years by the Kaplan-Meier methods. Anatomical predictors and risk stratification for MALE were analyzed by multivariate analysis. RESULTS: Freedom-from MALE was 47 ± 1% at 2 years. Lesion calcification, target vessel diameter<3.0 mm, lesion length>300 mm and no below-the-ankle (BA) run-off were positively associated with MALE by multivariate-analysis. The total number of risk factors was used to calculate the risk score for each limbs for subsequent categorization into 3 groups with 0 or 1 (low-risk), 2 (moderate-risk) and 3 or 4 (high-risk) factors. Freedom-from MALE at 2 year-rates was 59% in low-risk, 46% in moderate-risk, and 29% in high-risk, respectively. CONCLUSION: Target vessel diameter <3.0 mm, lesion calcification, lesion length > 300 mm and no-BA run-off were associated with MALE after infrapopliteal angioplasty. Risk stratification based on these predictors allows estimation of future incidence of MALE in CLI with isolated infrapopliteal lesions.