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In CO2-EOR (Enhanced Oil Recovery) and storage projects, there is a high risk of CO2 leakage into groundwater, which will not only affect storage effectiveness, but also cause a variety of environmental consequences. A monitoring system of CO2 leakage is essential to the safety of CO2-EOR and storage projects. Previous monitoring systems have been proposed through theoretical analysis, field test and indoor experiment. In this study, a modeling approach based on simulation of CO2 migration coupled with water-rock interactions in groundwater is proposed to support monitoring system development for CO2-EOR and storage projects. The simulation is undertaken using TOUGHREACT and applied to a case study in the Ordos Basin in China. The case study results indicate that the developed monitoring system has the advantage of offering a precise, timely and comprehensive monitoring scheme based on the dynamics of CO2 leakage and its effects on groundwater composition. [ABSTRACT FROM AUTHOR]

Summary: We assessed two electronic search tools that screen medical records for documented fractures. Both programs reliably identified patients with any fracture but missed individuals with minimal trauma fracture to different degrees. A hybrid tool combining the methodology of both tools is likely to improve the identification of those with osteoporosis. Purpose: Most patients who suffer a minimal trauma fracture remain undiagnosed, placing them at high risk of refracture. Case finding can be improved by electronic search tools that screen medical records for documented fractures. Here, we assessed the efficacy of two new programs, AES and XRAIT, in identifying patients with minimal trauma fracture. Methods: Each tool was applied to search the electronic medical record and/or radiology reports at two tertiary hospitals in Sydney, Australia, from 1 July to 31 December 2018. Samples of the extracted reports were then manually reviewed to determine the sensitivity of each program in detecting minimal trauma fractures. Results: At the two centers, AES detected 872 and 1364 cases, whereas XRAIT identified 1414 and 2180 patients with fractures, respectively. The true positive rate for "any fracture" was similar for both instruments (77–88%). However, the ability to detect "minimal trauma fractures" differed between programs and centers (53–75% accuracy), with each tool identifying separate subsets of patients. Concordance between both tools was less than half of the combined total number of minimal trauma fractures (43–45%). Considering the total number of minimal trauma fractures detected by both tools combined, AES correctly identified 52–55% of cases while XRAIT identified 88–93% of cases. Conclusion: Both programs reliably identified patients with any fracture but missed individuals with minimal trauma fracture to different degrees. Hybrid tools combining the methodology of XRAIT and AES are likely to improve the identification of patients who require investigation and treatment for osteoporosis. [ABSTRACT FROM AUTHOR]

Doping is a well-known strategy to enhance the electrochemical energy storage performance of layered cathode materials. Many studies on various dopants have been reported; however, a general relationship between the dopants and their effect on the stability of the positive electrode upon prolonged cell cycling has yet to be established. Here, we explore the impact of the oxidation states of various dopants (i.e., Mg2+, Al3+, Ti4+, Ta5+, and Mo6+) on the electrochemical, morphological, and structural properties of a Ni-rich cathode material (i.e., Li[Ni0.91Co0.09]O2). Galvanostatic cycling measurements in pouch-type Li-ion full cells show that cathodes featuring dopants with high oxidation states significantly outperform their undoped counterparts and the dopants with low oxidation states. In particular, Li-ion pouch cells with Ta5+- and Mo6+-doped Li[Ni0.91Co0.09]O2 cathodes retain about 81.5% of their initial specific capacity after 3000 cycles at 200 mA g−1. Furthermore, physicochemical measurements and analyses suggest substantial differences in the grain geometries and crystal lattice structures of the various cathode materials, which contribute to their widely different battery performances and correlate with the oxidation states of their dopants. Long-term efficient cycling stability is of paramount importance for the development of high-energy Li-ion batteries. Here, the authors investigate the effect of transition metal dopants on the electrochemical, morphological, and structural properties of Ni-rich cathode active materials. [ABSTRACT FROM AUTHOR]

Objective: We examined the associations of handgrip strength, upper arm circumference, and waist circumference with dementia among Singapore older adults. Design: Cross-sectional epidemiological study. Setting: Residential homes, day care centres, nursing homes and institutions. Participants: 2,565 men and women aged 60 years and above who participated in the Well-being of the Singapore Elderly (WiSE) study in 2013. Measurements: Socio-demographic correlates, dietary habits, health behaviours, grip strength, upper arm circumference, and waist circumference were collected. Grip strength was measured using a hand dynamometer with the dominant hand. Upper arm circumference was measured using a measuring tape around the thickest part of the upper arm while waist circumference measured in centimetres was measured at the narrowest part of the body between the chest and hips for women, and measured at the level of the umbilicus for men. Dementia was diagnosed using the 10/66 dementia diagnostic criteria. Results: Mean grip strength was 13.07 kg (SE=0.60) for people with dementia and 21.98 kg (SE=0.26) for people without dementia. After adjusting for all factors, grip strength remained significantly associated with dementia (p <0.0001). Upper arm circumference was associated with dementia (p <0.0001) but this association was only significant in the univariate analysis. Waist circumference was not significantly associated with dementia. Conclusions: Lower grip strength was independently associated with dementia in the older adult population in Singapore. Further research needs to be done to ascertain whether this association exists for specific types of dementia and look into the relationship of other anthropometric measurements with dementia in Singapore. [ABSTRACT FROM AUTHOR]

Objective: Dopamine transporter (DAT) imaging shows age-related decline of ligand binding in the normal striatum, a decline attributed to regulatory changes. We investigated if similar changes occur in the striatum of Parkinson's disease (PD) patients, using PET and [(18)F]FP-CIT, a ligand for DAT. Methods: We performed [(18)F]FP-CIT PET in 39 drug-naïve, de novo PD patients (age 56.0 ± 11.6 years, mean ± SD) and 34 healthy control subjects (age 52.3 ± 17.8). Parkinsonism was assessed by UPDRS III and Purdue pegboard. Binding ratios of [(18)F]FP-CIT were obtained in the putamen and caudate using the occipital cortex as reference. Results: Mean [(18)F]FP-CIT binding ratios in PD were 3.76 ± 0.74 (mean ± SD) in the putamen and 6.80 ± 1.05 in the caudate nucleus, significantly smaller than those in the healthy control (9.20 ± 1.38, 8.66 ± 1.12, respectively; p < 0.001 vs. healthy control for both). Regression analysis of [(18)F]FP-CIT binding ratios on age in healthy subjects showed significant correlations in the putamen (p < 0.001) and caudate nucleus (p < 0.001). Similar analysis in PD patients also showed significant correlations in the putamen (p = 0.015) and caudate nucleus (p = 0.018). The slope of regression in the putamen was -0.061 in the healthy control and -0.017 in PD, with significant differences between the two groups (p = 0.0003). In contrast, the regression slope in the caudate nucleus was -0.040 in the healthy control group, and -0.032 in the PD group with no significant differences between the two groups. Conclusions: Striatal [(18)F]FP-CIT binding showed significant age affects in patients with de novo PD after standardization for the severity of disease. The age effects were significantly smaller in PD patients than those in healthy subjects, but only in the putamen, not in the caudate nucleus. Given that age-related attrition of DA neurons is even in normal striatum, the uneven age effects in the parkinsonian striatum are likely to reflect the superimposition of disease-driven compensation on the aging effect. [ABSTRACT FROM AUTHOR]

The differentiation of and myelination by oligodendrocytes (OLs) are exquisitely regulated by a series of intrinsic and extrinsic mechanisms. As each OL can make differing numbers of myelin segments with variable lengths along similar axon tracts, myelination can be viewed as a graded process shaped by inhibitory/inductive cues during development. Myelination by OLs is a prime example of an adaptive process determined by the microenvironment and architecture of the central nervous system (CNS). in this review, we discuss how myelin formation by OLs may be controlled by the heterogeneous microenvironment of the CNS. Then we address recent findings demonstrating that neighboring OLs may compete for available axon space, and highlight our current understanding of myelin-based inhibitors of axonal regeneration that are potentially responsible for the reciprocal dialogue between OLs and determine the numbers and lengths of myelin internodes. Understanding the mechanisms that control the spatiotemporal regulation of myelinogenic potential during development may provide valuable insight into therapeutic strategies for promoting remyelination in an inhibitory microenvironment. [ABSTRACT FROM AUTHOR]

Current methods for studying central nervous system myelination necessitate permissive axonal substrates conducive to myelin wrapping by oligodendrocytes. We have developed a neuron-free culture system in which electron-spun nanofibers of varying sizes substitute for axons as a substrate for oligodendrocyte myelination, thereby allowing manipulation of the biophysical elements of axonal-oligodendroglial interactions. To investigate axonal regulation of myelination, this system effectively uncouples the role of molecular (inductive) cues from that of biophysical properties of the axon. We use this method to uncover the causation and sufficiency of fiber diameter in the initiation of concentric wrapping by rat oligodendrocytes. We also show that oligodendrocyte precursor cells display sensitivity to the biophysical properties of fiber diameter and initiate membrane ensheathment before differentiation. The use of nanofiber scaffolds will enable screening for potential therapeutic agents that promote oligodendrocyte differentiation and myelination and will also provide valuable insight into the processes involved in remyelination. [ABSTRACT FROM AUTHOR]

The human ABCB1 protein, (P-glycoprotein or MDR1) is a membrane-bound glycoprotein that harnesses the energy of ATP hydrolysis to drive the unidirectional transport of substrates from the cytoplasm to the extracellular space. As a large range of therapeutic agents are known substrates of ABCB1 protein, its role in the onset of multidrug resistance has been the focus of much research. This role has been of particular interest in the field of pharmacogenomics where genetic variation within the ABCB1 gene, particularly in the form of single nucleotide polymorphisms (SNPs), is believed to contribute to inter-individual variation in ABCB1 function and drug response. In this review we provide an update on the influence of coding region SNPs within the ABCB1 gene on drug pharmacokinetics. By utilizing the crystal structure of the mouse ABCB1 homolog (Abcb1a), which is 87% homologous to the human sequence, we accompany this discussion with a graphical representation of residue location for amino acids corresponding to human ABCB1 coding region SNPs. Also, an assessment of residue conservation, which is calculated following multiple sequence alignment of 11 confirmed sequences of ABCB1 homologs, is presented and discussed. Superimposing a 'heat map' of residue homology to the Abcb1a crystal structure has permitted additional insights into both the conservation of individual residues and the conservation of their immediate surroundings. Such graphical representation of residue location and conservation supplements this update of ABCB1 pharmacogenetics to help clarify the often confounding reports on the influence of ABCB1 polymorphisms on drug pharmacokinetics and response. [ABSTRACT FROM AUTHOR]

Mixed lineage leukemia 5 (MLL5) has been implicated in multiple aspects of cell physiology, such as hematopoiesis, cell cycle control and chromatin regulatory network. In this study, we present evidence that MLL5 is involved in the camptothecin (CPT)-induced p53 activation. CPT promoted the degradation of MLL5 protein in a time- and dose-dependent manner in actively replicating cells. The downregulation of MLL5 led to phosphorylation of p53 at Ser392, which was abrogated by exogenous overexpression of MLL5. In MLL5-knockdown cells, p53 protein was stabilized and bound to DNA with higher affinity, leading to activation of downstream genes. Co-immunoprecipitation showed that MLL5 preferentially interacted with the tetramerized form of p53, and knockdown of MLL5 promoted chromatin accumulation of p53 tetramers, suggesting that the association of MLL5 with p53 may prevent the p53 tetramers from binding to the chromatin target sites. The role of MLL5 in CPT-induced p53 activation was conserved in developing zebrafish, where CPT downregulated zebrafish Mll5 protein, and the microinjection of zebrafish mll5 mRNA substantially blocked the CPT-induced apoptosis. In summary, our study proposed MLL5 as a novel component in the regulation of p53 homeostasis and a new cellular determinant of CPT. [ABSTRACT FROM AUTHOR]

Polycrystalline SrNdFeAsF samples at various Nd-doping levels have been prepared by conventional solid-state synthesis close to ambient pressure. Susceptibility and resistivity were studied down to 4 K showing superconductivity competing with a low-temperature magnetic ordering and probably the coexistence of both, well into the superconducting region. The temperature dependence of the resistivity of all the Nd-doped samples clearly show the presence of this transition below 15 K, most likely originating from the magnetic ordering of Nd moments. This transition is gradually attenuated but not completely suppressed even at optimum-doping region at x≈0.54. The spin-density wave anomaly at 175 K survives up to 0.35 Nd-doping, while superconductivity occurs only above x=0.40. The maximum onset transition temperature, T, reaches as high as 54.3 K for x=0.70, but superconductivity disappears beyond that. The estimated upper critical fields, H, are high, with values exceeding 98 Tesla obtained from two samples of different doping level. [ABSTRACT FROM AUTHOR]

This retrospective analysis studied the impact of natural killer (NK) alloreactivity based on the missing ligand model, for a cohort of recipients undergoing haemopoietic stem cell transplant without T-cell depletion from HLA full-matched sibling donors. All patients received a uniform myeloablative conditioning regimen and prophylaxis for GVHD. A total of 151 patients were studied, including 62 patients with AML or myelodysplastic syndrome, 42 patients with ALL and 47 patients with CML. We found that 81% of patients had at least one missing KIR-ligand (KIR-L), and HLA-C1 allogroup homozygosity is present in 70% of patients. From multivariate analysis, we observed that the only consistently significant factor that was associated with superior survival was disease stage. Missing KIR-L, whether considering HLA-Bw and HLA-C alleles, without or with HLA-A ligands or narrowing to only HLA-C alleles alone to classify the number of missing KIR-L, did not have any impact on OS or relapse-free survival. This negative finding implies that as the KIR-L composition of recipient is not important in this matched non-T-depleted setting, further immunotherapeutic measures involving adoptive NK cell infusions have to be explored to exploit the benefit of NK alloreactivity for such transplants. [ABSTRACT FROM AUTHOR]

Topiramate is known to be efficacious in migraine prophylaxis, but its optimal dose has not been systematically studied in the Asian population. Here, we show that a fixed low dose of topiramate 25 mg/day is efficacious in migraine prophylaxis and also attest to advantages in terms of medication cost savings and more favourable side effect profile. [ABSTRACT FROM AUTHOR]

Execution of rapid ballistic movement is characterized by triphasic, alternating electromyographic bursts in agonist (AG) and antagonist (ANT) muscles. The ability to rapidly initiate movement and cancel ongoing action is a basic requirement for efficient control of motor function. Normal functioning of the cerebellum is necessary for the generation of AG and ANT muscle activity that should be both of appropriate magnitude and timing to control the dynamic phase of arm movements. We studied AG, ANT reaction time (RT), and RT differences in both motor activation (MA) and motor cancellation (MC) tasks, in response to an auditory stimulus. The results showed that right cerebellar transcranial magnetic stimulation (TMS) with a horizontally applied focal coil resulted in decreased AG RT and increased latency difference between AG RT and ANT RT (DIFF) in the ipsilateral upper limb during MC. No effect was apparent during sham stimulation, MA tasks, left upper limb recording, and other coil orientations. While the high correlation between AG and ANT RT suggests a close relationship in both MA and MC, significant DIFF changes point to an alteration of this relationship by TMS during MC. Although TMS resulted in significantly increased DIFF during MC tasks, this was not due to delayed ANT RT. This suggests that the short ANT burst observed invariably during MC may not be a cerebellum-generated response, but is derived from the cortical or subcortical level. The focal nature of our TMS coil and the horizontally effective orientation supports the hypothesis of interference with the parallel fiber system. Our findings contribute to the understanding of cerebellar neural networks involvement in movements, in particular, those pertaining to cessation of an ongoing action not previously addressed. [ABSTRACT FROM AUTHOR]

The time to neutrophil engraftment for adult patients after myeloablative double unit umbilical cord blood (UCB) transplantation is 23 days when the two units are given i.v. We hypothesized that the intra-BM injection (IBMI) of one of the two UCB units would reduce systemic loss of hematopoietic progenitors and shorten time to neutrophil recovery after myeloablation. Ten patients with a median age of 35 years were transplanted. The unit to be given by IBMI was randomly assigned; the other unit was given i.v. The median infused graft total nucleated cell dose was 3.7 × 107/kg with no difference between i.v. and IBMI units. All patients tolerated the procedure well, and there was no severe adverse event related to IBMI. The median time to neutrophil engraftment and plt recovery >50 000/μl was 21 and 69 days, respectively. In all, 9 of 10 patients engrafted, 5 with the i.v. unit and 4 with the IBMI unit; 7 of 8 evaluable patients developed acute GVHD and 5 of 10 patients died from treatment-related causes. Survival was 47% at 1 year. Despite safety of administration, IBMI of one of two UCB units did not shorten the time to neutrophil engraftment and offers no advantage over conventional double unit transplantation.Bone Marrow Transplantation (2009) 43, 935–940; doi:10.1038/bmt.2008.417; published online 12 January 2009 [ABSTRACT FROM AUTHOR]

The thalamus, a key information processing centre in facilitating sensory discrimination and cognitive processes, has been implicated in schizophrenia due to the increasing evidence showing structural and functional thalamic abnormalities. Glutamatergic abnormalities, in particular, have been examined since glutamate is one of the main neurotransmitters found in the thalamus. We aimed to review the existing literature (1978 till 2007) on post-mortem and in vivo studies of the various components of glutamatergic neurotransmission as well as studies of the glutamate receptor genes within the thalamus in schizophrenia. The literature search was done using multiple databases including Scopus, Web of Science, EBSCO host, Pubmed and ScienceDirect. Keywords used were “glutamate”, “thalamus”, “schizophrenia”, “abnormalities”, and “glutamatergic”. Further searches were made using the bibliographies in the main journals and related papers were obtained. The extant data suggest that abnormalities of the glutamate receptors as well as other molecules involved in glutamatergic neurotransmission (including glutamate transporters and associated proteins, N-methyl D-aspartate (NMDA) receptor-associated intracellular signaling proteins, and glutamatergic enzymes) are found within the thalamus in schizophrenia. There is a pressing need for more rapid replication of findings from post mortem and genetic studies as well as the promotion of multi-component or multi-modality assessments of glutamatergic anomalies within the thalamus in order to allow a better appreciation of disruptions in these molecular networks in schizophrenia. These and future findings may represent potential novel targets for antipsychotic drugs to ameliorate the symptoms of schizophrenia. [ABSTRACT FROM AUTHOR]

Evidence of LRRK2 haplotypes associated with Parkinson’s disease (PD) risk was recently found in the Chinese population from Singapore, and a common LRRK2 missense variant, Gly2385Arg, was independently detected as a putative risk factor for PD in the Chinese population from Taiwan. To test the association between the Gly2385Arg variant in a large case-control sample of Chinese ethnicity from Singapore, and to perform functional studies of the wild type and Gly2385Arg LRRK2 protein in human cell lines. In a case-control study involving 989 Chinese subjects, the frequency of the heterozygous Gly2385Arg genotype was higher in PD compared to controls (7.3 vs. 3.6%, odds ratio = 2.1, 95% CI: 1.1–3.9, P = 0.014); these values yield an estimated population attributable risk (PAR) of ∼4%. In a multivariate logistic regression analysis with the disease group (PD vs. controls) as the dependent variable and the genotype as an independent factor with adjustments made for the effect of age and gender, the heterozygous Gly2385Arg genotype remained associated with an increased risk of PD compared to wild type genotype (odds ratio = 2.67, 95% CI: 1.43–4.99, P = 0.002). The glycine at position 2385 is a candidate site for N-myristoylation, and the Gly2385Arg variant replaces the hydrophobic glycine with the hydrophilic arginine, and increases the net positive charge of the LRRK2 WD40 domain. In transfection studies, we demonstrated that both the wild type and Gly2385Arg variant LRRK2 protein localize to the cytoplasm and form aggregates. However, under condition of oxidative stress, the Gly2385Arg variant was more toxic and associated with a higher rate of apoptosis. Our study lends support to the contention that the Gly2385Arg is a common risk factor for PD in the Chinese population. Our bioinformatics and in-vitro studies also suggest that the Gly2385Arg variant is biologically relevant and it might act through pro-apoptotic mechanisms. [ABSTRACT FROM AUTHOR]

Isolated oral clefts, including cleft lip with/without cleft palate (CL/P) and cleft palate (CP), have a complex and heterogeneous etiology. Case-parent trios from three populations were used to study genes spanning chromosome 2, where single nucleotide polymorphic (SNP) markers were analyzed individually and as haplotypes. Case-parent trios from three populations (74 from Maryland, 64 from Singapore and 95 from Taiwan) were genotyped for 962 SNPs in 104 genes on chromosome 2, including two well-recognized candidate genes: TGFA and SATB2. Individual SNPs and haplotypes (in sliding windows of 2–5 SNPs) were used to test for linkage and disequilibrium separately in CL/P and CP trios. A novel candidate gene (ZNF533) showed consistent evidence of linkage and disequilibrium in all three populations for both CL/P and CP. SNPs in key regions of ZNF533 showed considerable variability in estimated genotypic odds ratios and their significance, suggesting allelic heterogeneity. Haplotype frequencies for regions of ZNF533 were estimated and used to partition genetic variance into among-and within-population components. Wright’s fixation index, a measure of genetic diversity, showed little difference between Singapore and Taiwan compared with Maryland. The tensin-1 gene (TNS1) also showed evidence of linkage and disequilibrium among both CL/P and CP trios in all three populations, albeit at a lower level of significance. Additional genes (VAX2, GLI2, ZHFX1B on 2p; WNT6–WNT10A and COL4A3–COL4A4 on 2q) showed consistent evidence of linkage and disequilibrium only among CL/P trios in all three populations, and TGFA showed significant evidence in two of three populations. [ABSTRACT FROM AUTHOR]

Ipsilateral motor evoked potentials (MEPs) in spinal cord surgery intraoperative monitoring is not well studied. We show that ipsilateral MEPs have significantly larger amplitudes and were elicited with lower stimulation intensities than contralateral MEPs. The possible underlying mechanisms are discussed based on current knowledge of corticospinal pathways. Ipsilateral MEPs may provide additional information on the integrity of descending motor tracts during spinal surgery monitoring. [ABSTRACT FROM AUTHOR]

PurposeTo compare the visual fields (VFs) and optic nerve head changes between obstructive sleep apnoea (OSA) in normotensive patients and an age-matched non-OSA population.DesignCase–control study.ParticipantsA total of 41 ethnic Chinese patients diagnosed with moderate to severe OSA referred from the Sleep Laboratory, ENT Department, Tuen Mun Hospital. A total of 35 age–matched non-OSA subjects recruited from the Ophthalmology Department, North District Hospital.MethodsComprehensive ophthalmological and systemic history, complete ophthalmological examination, including central-30 computerized perimetry for all studied patients.Main outcome measuresPolysomnographic data, VF indices, optic disc changesResultsIn the OSA arm, VF indices were significantly subnormal and the incidence of suspicious glaucomatous disc changes was four times higher than that of the control arm. None of the studied patients suffered from any form of anterior segment complications.ConclusionsModerate to severe OSA is associated with a higher incidence of VF defect and glaucomatous optic nerve changes.Eye (2006) 20, 38–42. doi:10.1038/sj.eye.6701785; published online 14 January 2005 [ABSTRACT FROM AUTHOR]

We provided data to show that the transcriptional activity of wildtype −258T in the parkin promoter region was significantly higher than the −258G variant in human cell lines. The transcriptional activity of wildtype −258T was significantly increased under oxidative stress by hydrogen peroxide, but this was not observed for the −258G variant. The transcriptional upregulation was significantly higher for wildtype −258T compared to −258G variant at 0.1, 0.2 and 0.4 mM of hydrogen peroxide. Similar results were obtained when the cells were treated with a proteasome inhibitor, MG132. Furthermore, in a case control study involving 753 subjects, we demonstrated that the parkin promoter −258G variant was associated with an increased risk of sporadic Parkinson’s disease (PD) in the elderly ethnic Chinese population. Our clinical and laboratory data provide corroborative evidence that some older individuals who have the −258G variant may have a higher risk of developing PD. [ABSTRACT FROM AUTHOR]

Background: Altered splicing of parkin under cellular stress could lead to changes in gene expression and altered protein activity. The causative role of parkin in sporadic Parkinson's disease (PD) is unknown. Objectives: We described a parkin splice variant (SV) in the substantia nigra and leukocytes of sporadic PD patients. Using a case control methodology, we investigated the exon 4 SV (E4SV) and wild-type parkin expression in the leukocytes of sporadic PD patients and healthy individuals. Methods/Results: We identified a parkin E4SV in the substantia nigra and leukocytes of sporadic PD patients and controls by reverse transcriptase-polymerase chain reaction (PCR). The exon 4 (122 bp) deletion resulted in a reading frame shift over the junction of exons 3–5 and a stop codon (tga) 17 bp downstream from exon 3. The translated truncated protein was associated with a total loss of the two-RING finger functional domain. Utilizing TaqMan real-time PCR with probes located across the junction of exons 3–4 or 3–5, we demonstrated an overexpression of E4SV/wild-type parkin ratio in the leukocytes of sporadic PD patients compared to age-, gender-, and race-matched controls (p«0.0005). A multivariate regression analysis demonstrated that the ratio of E4SV/wildtype parkin expression increased with age in PD patients, but this was not observed in the controls (p« 0.0005). Conclusion: The relative expression of E4SV/wild type parkin was increased in sporadic PD compared to healthy controls. Based on our observations, further functional studies to determine the pathophysiologic role of E4SV in sporadic PD patients will be of importance. [ABSTRACT FROM AUTHOR]

Objective: Many processes that are involved in cellular invasion, including blastocyst implantation, placental development, and rapidly growing tumors, occur in reduced oxygen environments. It has been surmised that oxygen tension could regulate the cytotrophoblast ability to differentiate and, as a consequence, to express proteins that are critical for placentation. The objective of the current investigation was therefore to test the hypothesis that placental tissues and trophoblast cells in culture, under low oxygen tension, release angiogenic factors that could affect vascular behavior and invasive potential, thus providing a link between abnormal placentation and maternal vascular abnormality.Methods: Functionally active term placental explant culture and trophoblast cultures were used to demonstrate the secretion profiles of angiogenin and vascular cell adhesion molecule-1 (VCAM-1), and the real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique was employed to demonstrate the mRNA expression under both normoxic and hypoxic conditions.Results:A significant increase in the secretion (P <.01) and mRNA expression (P <.01) of angiogenin and a signficant decrease in the secretion (P <.04) and mRNA expression (P <.03) of VCAM-1 from both term placental explants and trophoblast cultures subjected to hypoxia in vitro were observed.Conclusion: Because the primary defect in uteroplacental insufficiency is placental maldevelopment probably associated with hypoxia in situ, this study provides molecular evidence to indicate that the differential expression and secretion of angiogenic factors may play an important role in these pathologic conditions. [ABSTRACT FROM PUBLISHER]

The inhibitory motor control mechanisms in human singing and vocalization are not well understood. Using transcranial magnetic stimulation (TMS), we show that singing resulted in right-sided prolongation of ipsilateral silent period and bilateral reduction in contralateral silent period. Reading led to reduced contralateral silent period duration with right-sided TMS only, but no significant inhibitory changes, both ipsilateral and contralateral, were evident with humming. The findings support the presence of enhanced interhemispheric inhibitory motor interaction during singing, as opposed to reading tasks, in dynamic word generation coupled with production of melody. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only known curative therapy for patients with chronic myeloid leukemia (CML), but is associated with significant morbidity and mortality. The recent introduction of imatinib mesylate (STI-571) and reduced intensity transplant regimens has made the choice of primary treatment for patients with CML increasingly difficult. We have evaluated the outcome of 53 patients who have received allogeneic HSCT from human leukocyte antigen (HLA)-identical sibling donors between October 1985 and March 2002, determined the variables affecting the outcome, and tried to define indications for this aggressive approach. Successful engraftment occurred in 49 (98%) of evaluable patients. Acute graft-versus-host disease (GVHD) of grade II to IV severity was observed in 63% of the evaluable patients whereas the incidence of chronic GVHD was 57.5%. The Kaplan-Meier estimate of survival at 10 years was 54% [95% confidence interval (CI): 38–70%] and 31% (95% CI: 6–56%) for patients with first chronic phase and more advanced diseases, respectively. Multivariate analysis showed that younger age, absence of grade III-IV GVHD, the use of busulphan and cyclophosphamide (BuCy) as preparative regimen, and transplantation performed after January 1992 were factors associated with improved survival. Patients who were 30 years of age or younger who had transplantation done within 1 year after diagnosis during their first chronic phase of disease had a particularly good prognosis, with a probability of surviving 10 years of 72% (95% CI: 52–92%). We conclude that allogeneic HSCT remains a feasible option for Asian patients with CML. The most favorable outcome is observed in younger patients with early phase of the disease. [ABSTRACT FROM AUTHOR]

NZB mice develop an age-related malignant expansion of a subset of B cells, B-1 cells, with autocrine production of IL-10. IL-10, a pleiotropic cytokine with anti-inflammatory properties, is a potent growth and survival factor for malignant B cells. To further examine the in vivo requirement for IL-10 in the development and expansion of malignant B-1 clones in NZB mice, we developed a strain of homozygous IL-10 knockout (KO) mice on an NZB background. The NZB IL-10 KO mice develop peritoneal B-1 cells with approximately the same frequency as heterozygous and wild-type littermates. In contrast, the development of malignant B-1 cells in the peripheral blood and spleen, observed in wild-type NZB, rarely occurred in the NZB IL-10 KO. Phenotypic analysis of surface marker expression in splenic B cells indicated that, in contrast to the NZB with malignant B-1 splenic lymphoma, the surface marker expression of NZB IL-10 KO splenic B cells indicated that the majority of the B cells were typical B-2 cells. In the absence of IL-10, spontaneously activated B cells and antiapoptotic gene expression were reduced and lymphoma incidence was decreased. These results indicate that IL-10 is a critical factor for the progression of this B-cell malignant disease.Leukemia (2004) 18, 597-606. doi:10.1038/sj.leu.2403244 Published online 8 January 2004 [ABSTRACT FROM AUTHOR]

Isothermal transformation from austenite in an Fe-9.14 pct Ni alloy has been studied by optical metallography and examination by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In the temperature range 565 °C and 545 °C, massive ferrite ( α q ) forms first at prior austenite grain boundaries, followed by Widmanstätten ferrite ( α W ) growing from this grain boundary ferrite. Between 495 °C and 535 °C, Widmanstätten ferrite is thought to grow directly from the austenite grain boundaries. Both these transformations do not go to completion and reasons for this are discussed. These composition invariant transformations occur below T 0 in the two-phase field ( α+ γ). Previous work on the same alloy showed that transformation occurred to α q > and α W on furnace cooling, while analytical TEM showed an increase of Ni at the massive ferrite grain boundaries, indicating local partitioning of Ni at the transformation interface. An Fe-3.47 pct Ni alloy transformed to equiaxed ferrite at 707 °C ±5 °C inside the single-phase field on air cooling. This is in agreement with data from other sources, although equiaxed ferrite in Fe-C alloys forms in the two-phase region. The application of theories of growth of two types of massive transformation by Hillert and his colleagues are discussed. [ABSTRACT FROM AUTHOR]

The crystallographic normal mode refinements of myoglobin at a wide range of temperature from 40 K to 300 K were carried out to study the temperature dependence of the internal atomic fluctuations. The refinement method decomposes the mean square displacement from the average position, <Δr[sup 2] >, into the contributions from the internal degrees of freedom and those from the external degrees of freedom. The internal displacements show linear temperature dependence as <Δr[sup 2] >=αT+β, throughout the temperature range measured here, and exhibit no obvious change in the slope α at the dynamical transition temperature (T[sub c] =ca. 180 K). The slope α is practically the same as the value predicted theoretically by normal mode analysis. Such linear dependence is considered to be due to the following reason. The crystallographic Debye-Waller factor represents the static distribution caused by convolution of temperature-dependent normal mode motions and a temperature-independent set of the conformational substates. In contrast, Mössbauer absorption spectroscopy shows a clear increase in the gradient α at T[sub c] . This difference from X-ray diffraction originates from the incoherent nature of the Mössbauer effect together with its high-energy resolution, which yields the self-correlation, and the temporal behavior of individual Fe atoms in the myoglobin crystal. [ABSTRACT FROM AUTHOR]

IL-10 is overexpressed in human chronic lymphocytic leukemia (CLL), and is an autocrine growth factor involved in the development of malignant B1 clones in NZB mice, a murine model for CLL. Antisense IL-10 oligonucleotide treatment induces apoptosis and cell cycle disruption in these cells both in vitro and in vivo. In addition, NZB IL-10 knock-out mice fail to develop the B-1 clones. Dampening of IL-10 protein production via antisense IL-10 oligonucleotide treatment is correlated with decreased p27/Kipl protein expression which results in increased cyclin D2, cyclin E and cyclin A associated kinase activity. The action of the antisense oligonucleotides is through alterations in cell cycle regulation, resulting in accelerated cell cycle progression, a G2/M block which culminates in apoptosis induction in the malignant cells. This implies that the role of IL-10 as an autocrine growth factor in malignant B-1 cells lies in its ability to inhibit apoptosis induction through the maintenance of sustainable cell cycle progression in malignant cells. Genes and Immunity (2001 ) 2, 239-247. [ABSTRACT FROM AUTHOR]

Our aim was to determine the relative merits of short and long echo times (TE) with single-shot echo-planar imaging for imaging cerebral lesions such as multiple sclerosis. We examined seven patients with clinically definite multiple sclerosis were imaged at 1.5 T. Patients were scanned with spin-echo, single-shot echo-planar imaging, using TEs of 45, 75, 105, and 135 ms. Region of interest (ROI) measurements were performed on 36 lesions at or above the level of the corona radiata. The mean image contrast (IC) was highest (231.1) for a TE of 45 ms, followed by 75 ms (218.9), 105 ms (217.9), and 135 ms (191.6). When mean contrast-to-noise ratios (C/N) were compared, the value was again highest (29.7) for TE 45 ms, followed by 75 ms (28.9), 105 ms (28.5), and 135 ms (26.3). In a lesion-by-lesion comparison, TE 45 ms had the highest IC and C/N in the largest number of cases (50 % and 47.2 %, respectively). IC and C/N for TE 45 ms were superior to those of 75 ms in 64 % and 58 %, respectively. These results support the use of relatively short TEs for single-shot echo-planar imaging in the setting of cerebral lesions such as multiple sclerosis. [ABSTRACT FROM AUTHOR]

Acute graft-versus-host disease (aGVHD) remains a major barrier to a wider application of allogeneic bone marrow transplantation (BMT). Although this complication is mainly dependent on donor-derived T lymphocytes, very little information is available concerning the mechanism of lethality. In this study, we investigated both the expression of Fas/Fas-ligand (FasL) and lymphocyte subset reconstitution in patients who underwent HLA-matched related allogeneic BMT (n = 16) and normal donors (n = 10), and several distinct features were observed. First, the reconstitutions of CD3+ and CD56+ cells were different between the aGVHD+ and aGVHD- group. In particular, the percentage of CD3-CD56+ cells was significantly decreased in patients with aGVHD (P < 0.01). second, the expansion of cd8+ (P = 0.01) and CD8+ CD28- T cells (P = 0.03) was a characteristic finding in patients with aGVHD. Finally, we found that the percentages of Fas+CD8+, Fas+HLA-DR+ and FasL+ CD8+ cells were significantly increased. Fas antigen was highly coexpressed on most of the lymphocyte subsets, especially on CD8+ cells (P < 0.01), and also, significantly higher coexpression of fasl on cd8+ cells was found in patients with aGVHD (P < 0.01). in summary, an increase in the percentage of cd8+ cells which express Fas and its ligand in patients with aGVHD after BMT points to a possible role for the Fas/FasL pathway in the effector phase of aGVHD. [ABSTRACT FROM AUTHOR]

The morphological changes occurring in Blastocystis hominis at different time points following in vitro encystment were studied by electron microscopy. The following stages of the parasite were sequentially seen: (a) the amoebic form, which was irregular in shape, with a majority of the organelles being concentrated at the condensed cytoplasmic region; (b) the pre-cystic form, which was rounded and had an electron-dense material forming a homogeneous wall around the central body; and (c) the cystic form, which had a very prominent, thick osmiophilic electron-dense wall, within which there were many inclusions and possibly reproductive granules. The amoebic form appeared to be an intermediate stage between the vacuolar form and the pre-cystic form, as this stage allowed the parasite to ingest bacteria to enhance encystment. The pre-cystic stage had previously been shown in experimental infection to be infective. The role of the cystic stage in producing infection is currently being investigated. [ABSTRACT FROM AUTHOR]

Fertilized medaka ( Oryzias latipes) eggs were cytoplasmically injected with the chloramphenicol acetyltransferase (CAT) gene encompassed in supercoiled and linear plasmid DNA, as well as in intact recombinant phage particles and DNA isolated from the phage. Expression for the CAT plasmid DNA was highest at the gastrula/neurula stage, while for the DNA of the phage, it peaked in the 1-week old embryo; then expression declined but was still detectable in early adulthood (4 weeks post injection). Following the fate of exogenous DNA, an extensive replication was observed in early embryogenesis, and DNA was still found 4 weeks after injection, suggesting a possibility of integration. The system is useful as a transient expression system for the analysis of early developmental genes in particular, but also as a test system for the analysis of cloned genes of interest for the farming of economically important fish species. The fact that DNA transferred in intact phage particles or its DNA is functionally active opens the possibility to introduce larger DNA pieces (20 kb), e.g., for the functional test of larger and more distant control regions. [ABSTRACT FROM AUTHOR]

Eperythrozoon coccoides has been found in laboratory mice in Brisbane. Its presence can be a source of confusion in attempts to isolate infective agents in mice. Observations were made on the course of the experimental infection in unsplenectomized mice. The infection is characterized by splenomegaly, which is well marked from 7 to 28 days after inoculation. Histologically, the spleen shows hyperplasia of the lymphatic tissue and congestion of the red pulp. At 14 days after inoculation, a high titre (10-6 to 10-8) of infectivity was found in the blood, although eperythrozoa are rarely seen in blood smears of infected unsplenectomized mice. No concentration of infectivity was found in other organs or tissues. The infection appears to be self-limited and to terminate naturally after about 12 to 21 weeks. An attempt failed to reinfect four mice ten months after their original inoculation. [ABSTRACT FROM AUTHOR]

We have described the familial occurrence of hyperphosphataemia in 2 Irish sisters. There was evidence of ectopic calcification in the vertebral discs, large arteries leading to premature peripheral vascular ischaemia, placenta and the soft tissue of the thigh and the history of renal stone formation. The clinical findings do not fit easily into any previously described disorder and may be a distinct entity. The heredity is uncertain but may be a recessive sex linked pattern. We also report experience with acetazolamide acutely and chronically over 2 yr in an attempt to mobilise the phosphate by increasing its renal excretion. [ABSTRACT FROM AUTHOR]

We showed that the frequency of a LRRK2 variant (c.4883G > C, R1628P) was higher in Parkinson’s disease (PD) compared to controls (8.4 vs. 3.4%, P = 0.046, OR 2.5, 95% CI 1.1–5.6). In the multivariate logistic regression (with adjustments made for the effect of age, age of onset, and gender), the heterozygous R1628P genotype was associated with an increased risk of PD compared to controls (OR 3.3, 95% CI 1.4– 7.9, P = 0.007). We provided an independent confirmation that the R1628P variant increases the risk of PD among Chinese. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) has been known to increase diagnostic accuracy in differentiating benign and malignant lung lesions and to improve identification of lymph node and extrathoracic metastasis in pulmonary neoplasms. In this review, the authors describe the spectrum of integrated PET/CT findings on neuroendocrine (NE) tumors of the lung. We also demonstrate the usefulness of this imaging modality in patients with known or suspected NE tumors of the lung.