Risk of developing Parkinson's disease among patients with asthma: a nationwide longitudinal study.

BACKGROUND: A cross-sectional retrospective study suggested a link between allergic diseases and Parkinson's disease. However, the temporal association between asthma and Parkinson's disease remains unknown. METHODS: From the Taiwan National Health Insurance Research Database, 10 455 patients who were diagnosed with asthma between 1998 and 2008 and aged ≥45 years and 41 820 age- and sex-matched controls were selected for our study and observed until the end of 2011. Those who developed Parkinson's disease during the follow-up period were identified. We also examined the asthma severity, as indicated by the frequency of admission (times per year) for asthma exacerbation, and the risk of subsequent Parkinson's disease. RESULTS: Patients with asthma had an increased risk of developing Parkinson's disease (hazard ratio [HR]: 3.10, 95% confidence interval [CI]: 2.20-4.36) after we adjusted for demographic data, health system use, medical comorbidities, and medication use. Sensitivity tests yielded consistent findings after we excluded observations on the first year (HR: 2.90, 95% CI: 2.04-4.13) and first 3 years (HR: 2.46, 95% CI: 1.64-3.69). Patients with asthma who had more frequent admissions (times per year) during the follow-up period exhibited a greater risk of subsequent Parkinson's disease (>2: HR: 16.42, 95% CI: 5.88-45.91; 1-2: 12.69, 95% CI: 5.03-31.71; 0-1: HR: 2.92, 95% CI: 1.91-4.49). CONCLUSION: Patients with asthma had an elevated risk of developing Parkinson's disease later in life, and we observed a dose-dependent relationship between greater asthma severity and a higher risk of subsequent Parkinson's disease.

Site- and energy-selective intramolecular manipulation of polychlorinated biphenyl (PCB) molecules.

We demonstrate the conversion of an adsorbed precursor state of polychlorinated biphenyl (PCB) molecules on the Si(111)-7 × 7 surface at room temperature into a more stable configuration via site- and energy-selective atomic manipulation in the scanning tunneling microscope (STM). Whereas molecular desorption is maximized by electron injection into the chemisorbed molecular ring at low voltage, injection into the physisorbed molecular ring above a threshold voltage (2.5 V) favors the reconfiguration of the bonding. The results clearly demonstrate both intramolecular charge localization and intramolecular charge transportation as key ingredients in the atomic manipulation of individual polyatomic molecules.

Streamflow calculation for medium-to-small rivers in data scarce inland areas.

Inland streamflow estimation is essential in global water supply and environment protection. In data-scarce areas a highly efficient way of estimating streamflow is through remote sensing methods. However, high requirement of most previous methods on ground-measured data hinder their wide use in data-scarce areas. Therefore, this paper presented a new framework for estimation of streamflow in medium-to-small rivers with few ground measurements by using high-resolution unmanned aerial vehicle (UAV) imagery. A new Virtual Hydraulic Radius (VHR) method was proposed to complement AMHG (at-many-stations hydraulic geometry), a method not requiring any ground measurements when global parameters are used (global-AMHG) in large-scaled rivers but yielding great uncertainties in smaller scaled rivers, thus creating a VHR-AMHG method for medium-to-small rivers. The accuracy verification of the proposed method was performed by comparing it to field measurement data and the global parameters of the original AMHG (global-AMHG). Results showed that the root mean square error calculated from VHR-AMHG was 32.15 m3/s, while that from global-AMHG was 305.65 m3/s, indicating that the VHR-AHRG method yields a significantly higher accuracy for streamflow estimation for medium-to-small rivers. We found that regardless of the size of the river, AMHG is not applicable for rivers having excessively small b values in the equation w = aQb (low-b rivers). For medium-to-small rivers with b < 0.25, AMHG is not recommended. The accuracy of the original AMHG method is limited by the initial value of the model parameters and the condition that the congruent discharge (Qc) has to be within the range of observational discharge. The initial value setting of the model parameters significantly impacts the calculation accuracy. The VHR-AMHG method is able to overcome the deficiencies of the original AMHG, i.e. being overly dependent on the initial value setting with long-series known discharge data. It also eliminates the limitation of the Qc condition, as it achieves a higher accuracy for rivers in which Qc does not satisfy the condition compared to using global-AMHG on rivers that actually meet the condition, thus greatly expanding its usage scope. Thus VHR-AMHG method can provide detailed data on the spatial and temporal distribution of regional and national streamflow for governments and stakeholders, and offer scientific data support for wisely making water supply polices and sustainably protecting eco-environment.

Atomically resolved real-space imaging of hot electron dynamics.

The dynamics of hot electrons are central to understanding the properties of many electronic devices. But their ultra-short lifetime, typically 100 fs or less, and correspondingly short transport length-scale in the nanometre range constrain real-space investigations. Here we report variable temperature and voltage measurements of the nonlocal manipulation of adsorbed molecules on the Si(111)-7 × 7 surface in the scanning tunnelling microscope. The range of the nonlocal effect increases with temperature and, at constant temperature, is invariant over a wide range of electron energies. The measurements probe, in real space, the underlying hot electron dynamics on the 10 nm scale and are well described by a two-dimensional diffusive model with a single decay channel, consistent with 2-photon photo-emission (2PPE) measurements of the real time dynamics.

Depression of prothymosin alpha production in murine thymus correlates with staphylococcal enterotoxin-B-induced immunosuppression [corrected].

Prothymosin alpha [corrected] (ProT alpha) and thymosin beta 4 [corrected] (T beta 4) were isolated from murine thymus and characterized by microsequence analysis. Murine T beta 4 has an identical sequence to bovine T beta 4, whereas murine ProT alpha is highly homologous to rat Pro T alpha. Murine Pro T alpha differs from rat Pro T alpha at two positions, Glu100 and Asp108 of the rat sequence are substituted by aspartic and glutamic acid, respectively, in murine Pro T alpha. The amount of Pro T alpha in murine thymus was found to be reduced after in vivo treatment with staphylococcal enterotoxin B [corrected] (SEB), a superantigen which stimulates T cells bearing specific V beta receptors. Results from the anti-SRBC (sheep erythrocyte) plaque-forming cell assay showed that the antibody response of the spleen cells from these animals was also suppressed. On the other hand, the amount of T beta 4 was not changed significantly. Our studies suggest that the suppression of SEB on antibody response correlates with the depression of Pro T alpha production in the thymus.

Telomerase activity in rat liver allografts.

BACKGROUND: Telomerase activity in grafts may be involved in the alteration of cellular senescence after transplantation or its relevant immunological events. METHODS: At the age of 20 weeks, donor livers harvested from DA (RT1a) were orthotopically transplanted into PVG (RT1c) or LEW (RT1(1)) rats. Rats having undergone orthotopic liver transplantation (OLT; DA-PVG) naturally overcome rejection, whereas all OLT (DA-LEW) rats die from acute rejection within 14 days. Telomerase activity in liver allografts was measured at various intervals post OLT. RESULTS: At day 7 when the most severe rejection episode was observed in OLT (DA-LEW) and OLT (DA-PVG), the telomerase activity was significantly higher than in syngeneic OLT (DA-DA) rats, in which no rejection occurred. Telomerase activity in tolerogenic OLT (DA-PVG) livers remained elevated for at least 2 months. CONCLUSION: These results suggest that telomerase activity in allogeneic OLT livers may reflect regenerating hepatocytes or activation of lymphocytes and/or hematopoietic stem cells associated with rejection or tolerance.

Assessment of donor fatty livers for liver transplantation.

AIM: The effect of fatty liver on graft survival, especially with reference to macrovesicular and microvesicular steatosis, is still uncertain. This preliminarily study was designed to create a noninvasive method for the quantification of the hepatic fat content in vivo and to establish provisional criteria for the assessment of fatty donor livers before liver transplantation among transplant surgeons, radiologists, and pathologists. METHODS AND MATERIALS: Different degrees of rat fatty liver model were established by feeding rats a diet deficient in choline and methionine for different periods of time. Computed tomography (CT) with test tubes containing variable percentages of fat equivalent substance were used to assess the severity of fatty change of the rat liver. This was then correlated with the histological classification, level of hepatic enzymes, and graft survival. RESULTS: Linear correlation between the fat volume fraction added to the test tubes and CT density were found. The process of producing a fatty liver via diet alteration peaked at week 3. At this time hepatic enzymes, radiological fat content, and posttransplantation survival were worse (P=0.013), compared with other time points. Radiological assessment of fatty liver correlated well with survival and serum glutamic oxaloacetic transaminase and glutamic pyruvate transaminase levels. CONCLUSION: Severe microvesicular steatosis does not influence recipient survival, however, macrovesicular steatosis affects graft survival. Caliber CT is a practical and simple method that allows an accurate noninvasive quantitative assessment of hepatic fatty infiltration. It has potential to be a useful parameter for the assessment of donor livers for clinical liver transplantation.

A transient increase in endogeneous erythropoietin levels after paediatric liver transplantation.

We investigated whether liver transplantation affects endogeneous erythropoietin (EPO) synthesis. Serum EPO levels were measured before transplantation and during the peri-transplant period in ten consecutive paediatric patients who had received a liver allograft without recombinant EPO therapy. All patients were anaemic on post-operative day 1 (POD 1); however, the haemoglobin levels of three patients gradually increased and required phlebotomy on POD 5-9. The serum levels of EPO in all patients were within the normal range before surgery, but six of the ten patients had a transient increased level of EPO at 1248 h after transplantation. A transient increase of endogeneous EPO following paediatric liver transplantation may be associated with extramedullary erythropoiesis in human liver grafts.

Clusterin may be involved in rat liver allograft tolerance.

Little is known about the possible role of complement inhibitors on tolerance induced by liver allografts. Clusterin, which is a plasma glycoprotein, inhibits cytolytic membrane attack complex (MAC) of complement by binding to soluble C5b-7 complex. The role of clusterin in relation to the naturally achieved tolerance in a rat orthotopic liver transplantation (OLT) has not been investigated before. Here we determined the kinetics of clusterin expression at different post-transplantation time points in a tolerogenic model (DA-PVG) where rejection was naturally overcome without any immunosuppressive drugs in comparison with the syngenic OLT model (DA-DA). Peripheral blood and liver tissues were taken from OLT at various post-operative time points. A strong expression of soluble clusterin was observed on post-transplantation day 7, which occurred at the peak of the rejection in this tolerogenic OLT model. The expression of clusterin remained strong even after tolerance was achieved. The intensity of clusterin expression was much stronger when compared with the syngenic OLT (DA-DA) model after OLT. A strong expression of clusterin mRNA was also observed in the tolerogenic model on post-OLT day (POD) 7 and the expression persisted when compared with the syngenic model on post-OLT day 60. Our data have shown that the strongest levels of clusterin during the reaction phase in tolerogenic OLT may be involved in tolerance induction.

Identification of the indoleamine 2,3-dioxygenase nucleotide sequence in a rat liver transplant model.

A tryptophan catabolizer, indoleamine 2,3-dioxygenase (IDO) is highly expressed in the placenta and plays an essential role in maternal tolerance. Recent data have shown that the administration of an IDO inhibitor blocked not only maternal tolerance but also liver allograft tolerance. However, little is known about the induction of IDO in liver allografts, although a gene specific for tryptophan 2,3-dioxygenase (TDO) is believed to be expressed in the liver. In the present study, we investigated whether IDO is induced in liver allografts. Synthetic oligonucleotide primers based on the mouse IDO cDNA sequence were used to amplify RNA derived from livers of donor, syngeneic or allogeneic OLT rats. RNA encoding IDO was induced in the rat allogeneic liver after orthotopic liver transplantation (OLT), but not in syngeneic OLT. The rat nucleotide sequence of the RT-PCR products obtained from OLT livers revealed identities of 89% homology to the mouse IDO and of 68% to the human IDO. This study demonstrated the presence of RNA encoding IDO in allogeneic OLT livers, which may be involved in the immune response after liver transplantation.

Repeated hypotensive episodes due to hepatic outflow obstruction during liver transplantation in adult patients.

We report two cases of unusual repeated hypotension, decreased cardiac output, decreased mixed venous oxygen saturation, decreased central venous pressure, pulmonary artery pressure, and pulmonary wedge pressure after the completion of all vascular anastamoses of liver transplantation. These unstable hemodynamics appear to reflect a clinically relevant picture of hypovolemia. However, the real cause was partial hepatic outflow obstruction. The obstruction was suspected because hypotension was alleviated by elevating the full-sized liver graft ventrally and to the left. Doppler ultrasound examination confirmed that the flow velocity of the hepatic vein outflow was insufficient when the liver fell to its resting position in the right hepatic fossa. An additional side-to-side cavo-caval anastomosis resolved the problem in one patient, whereas the other required not only the additional anastomosis, but also application of a tissue expander filled with 770 mL normal saline beneath the liver to eliminate the obstruction. We emphasize that obstruction of the hepatic outflow causes only temporal hypovolemia because of a decrease of venous return and that treatment of this complication should be surgical intervention to relieve the obstruction. Blind resuscitation with fluids will not solve the problem and, in fact, may result in fluid overload with subsequent complications.