bluuebunny/crossref_metadata_2025 huggingface dataset:
Impulse Propagation along Thalamocortical Fibers Can Be Detected Magnetically outside the Human Brain
Authors: Kimura Tomoaki , Ozaki Isamu , Hashimoto Isao
Published: November 2008

Orchestrating cortical network activity with synchronous oscillations of neurons across distant regions of the brain underlies information processing in humans (Knight, 2007) and monkeys (Saalmann et al., 2007; Womelsdorf et al., 2007). Frequencies of oscillatory activities depend, to a considerable extent, on the length and conduction velocity of the tracts connecting the neural areas that participate in oscillations (Buzsáki, 2006). However, the impulse propagation along the fiber tracts in the white matter has never been visualized in humans. Here, we show, by recording magnetoencephalogram (MEG) following median nerve stimulation, that a magnetic field component, we labeled “M15,” changes dynamically within 1.6–1.8 ms before the onset of magnetic M20 response generated from the primary somatosensory cortex. This new M15 component corresponds to the intracellular depolarizing action current in the thalamocortical fibers propagating with the mean conduction velocity of 29 m/s. The findings challenge the traditional view that MEG is blind to the activity of deep subcortical structures. We argue that the MEG technique holds the promise of providing novel information in impulse transmissions along not only the thalamocortical pathway but also other fiber tracts connecting distant brain areas in humans.
Optical Reporters for the Conformation of α-Synuclein Reveal a Specific Interaction with Mitochondria
Authors: Nakamura Ken , Nemani Venu M. , Wallender Erika K. , Kaehlcke Katrin , Ott Melanie , Edwards Robert H.
Published: November 2008

The aggregation of abnormally folded proteins is a defining feature of neurodegenerative disease, but it has not previously been possible to assess the conformation of these proteins in a physiologically relevant context, before they form morphologically recognizable aggregates. We now describe FRET-based reporters for the conformation of α-synuclein, a protein central to the pathogenesis of Parkinson's disease (PD). Characterizationin vitroshows that α-synuclein adopts a relatively “closed” conformation in solution that converts to “open” on membrane binding. In living cells, the closed conformation predominates. In neurons, however, cell bodies contain a much larger proportion of the open conformation than synaptic boutons. To account for these differences, we also used the reporters to characterize the interaction with native membranes. We find that the conformation of α-synuclein responds selectively to mitochondria, indicating a direct link between α-synuclein and an organelle strongly implicated in the pathogenesis of PD.
MicroRNA-338 Regulates Local CytochromecOxidase IV mRNA Levels and Oxidative Phosphorylation in the Axons of Sympathetic Neurons
Authors: Aschrafi Armaz , Schwechter Azik D. , Mameza Marie G. , Natera-Naranjo Orlangie , Gioio Anthony E. , Kaplan Barry B.
Published: November 2008

MicroRNAs (miRs) are evolutionarily conserved, noncoding RNA molecules of ∼21 nt that regulate the expression of genes that are involved in various biological processes, such as cell proliferation and differentiation. Previously, we reported the presence of a heterogeneous population of mRNAs present in the axons and nerve terminals of primary sympathetic neurons to include the nuclear-encoded mitochondrial mRNA coding for COXIV. Sequence analysis of the 3′UTR of this mRNA revealed the presence of a putative binding site for miR-338, a brain-specific microRNA. Transfection of precursor miR-338 into the axons of primary sympathetic neurons decreases COXIV mRNA and protein levels and results in a decrease in mitochondrial activity, as measured by the reduction of ATP levels. Conversely, the transfection of synthetic anti-miR oligonucleotides that inhibit miR-338 increases COXIV levels, and results in a significant increase in oxidative phosphorylation and also norepinephrine uptake in the axons. Our results point to a molecular mechanism by which this microRNA participates in the regulation of axonal respiration and function by modulating the levels of COXIV, a protein which plays a key role in the assembly of the mitochondrial cytochromecoxidase complex IV.
Neural Correlates of Decisions and Their Outcomes in the Ventral Premotor Cortex
Authors: Pardo-Vazquez Jose L. , Leboran Victor , Acuña Carlos
Published: November 2008

Selection of the appropriate action in a changing environment involves a chain of events that goes from perception through decision to action and evaluation of the outcomes. What and where in the brain are the correlates of these events? The ventral premotor cortex (PMv) is a candidate because (1) it is involved in sensory transformations for visually guided actions and in perceptual decisions, and (2) it is connected with sensory, motor, and high-level cognitive areas related to performance monitoring. Therefore, we hypothesized that it would be the site for representing sensory perception for action and for evaluating the decision consequences. Trained monkeys were required to discriminate the orientation of two lines showed in sequence and separated by a delay. Monkeys compared the orientation of the second line with the memory trace of the first and communicated whether the second was to the left or to the right of the first. Here we show that the activity of PMv neurons reflected (1) the first stimuli and its memory trace during the delay and comparison periods, (2) its comparison with the second stimuli, including the strength of the evidence, and (3) the result of the discrimination (choice). After the monkeys reported the choice, there were neurons that only encoded the choices, others only the outcomes, and others the choices and outcomes together. The representation of task cues, decision variables, and their outcomes suggest a role of PMv as part of a supervisory network involved in shaping future behavior and in learning.
A Structural MRI Study of Human Brain Development from Birth to 2 Years
Authors: Knickmeyer Rebecca C. , Gouttard Sylvain , Kang Chaeryon , Evans Dianne , Wilber Kathy , Smith J. Keith , Hamer Robert M. , Lin Weili , Gerig Guido , Gilmore John H.
Published: November 2008

Brain development in the first 2 years after birth is extremely dynamic and likely plays an important role in neurodevelopmental disorders, including autism and schizophrenia. Knowledge regarding this period is currently quite limited. We studied structural brain development in healthy subjects from birth to 2. Ninety-eight children received structural MRI scans on a Siemens head-only 3T scanner with magnetization prepared rapid gradient echo T1-weighted, and turbo spin echo, dual-echo (proton density and T2 weighted) sequences: 84 children at 2–4 weeks, 35 at 1 year and 26 at 2 years of age. Tissue segmentation was accomplished using a novel automated approach. Lateral ventricle, caudate, and hippocampal volumes were also determined. Total brain volume increased 101% in the first year, with a 15% increase in the second. The majority of hemispheric growth was accounted for by gray matter, which increased 149% in the first year; hemispheric white matter volume increased by only 11%. Cerebellum volume increased 240% in the first year. Lateral ventricle volume increased 280% in the first year, with a small decrease in the second. The caudate increased 19% and the hippocampus 13% from age 1 to age 2. There was robust growth of the human brain in the first two years of life, driven mainly by gray matter growth. In contrast, white matter growth was much slower. Cerebellum volume also increased substantially in the first year of life. These results suggest the structural underpinnings of cognitive and motor development in early childhood, as well as the potential pathogenesis of neurodevelopmental disorders.
Monomeric IgG Is Neuroprotective via Enhancing Microglial Recycling Endocytosis and TNF-α
Authors: Hulse Raymond E. , Swenson Wade G. , Kunkler Phillip E. , White David M. , Kraig Richard P.
Published: November 2008

In brain, monomeric immunoglobin G (IgG) is regarded as quiescent and only poised to initiate potentially injurious inflammatory reactions via immune complex formation associated with phagocytosis and tumor necrosis factor α (TNF-α) production in response to disease. Using rat hippocampal slice and microglial cultures, here we show instead that physiological levels (i.e., 0.2–20 μg/ml) of monomeric IgG unassociated with disease triggered benign low-level proinflammatory signaling that was neuroprotective against CA1 area excitotoxicity and followed a U-shaped or hormetic dose–response. The data indicate that physiological IgG levels activated microglia by enhancing recycling endocytosis plus TNF-α release from these cells to produce the neuroprotection. Minocycline, known for its anti-inflammatory and neuroprotective effects when given after disease onset, abrogated IgG-mediated neuroprotection and related microglial effects when given before injury. In contrast, E-prostanoid receptor subtype 2 (EP2) activation, which served as an exemplary paracrine stimulus like the one expected from neuronal activity, amplified IgG-mediated increased microglial recycling endocytosis and TNF-α production. Furthermore, like monomeric IgG these EP2 related effects took days to be effective, suggesting both were adaptive anabolic effects consistent with those seen from other long-term preconditioning stimuli requiringde novoprotein synthesis. The data provide the first evidence that brain monomeric IgG at physiological levels can have signaling function via enhanced recycling endocytosis/TNF-α production from microglia unassociated with disease and that these IgG-mediated changes may be a means by which paracrine signaling from neuronal activity influences microglia to evoke neuroprotection. The data provide further support that low-level proinflammatory neural immune signaling unassociated with disease enhances brain function.
Specific Glial Populations Regulate Hippocampal Morphogenesis
Authors: Barry Guy , Piper Michael , Lindwall Charlotta , Moldrich Randal , Mason Sharon , Little Erica , Sarkar Anindita , Tole Shubha , Gronostajski Richard M. , Richards Linda J.
Published: November 2008

The hippocampus plays an integral role in spatial navigation, learning and memory, and is a major site for adult neurogenesis. Critical to these functions is the proper organization of the hippocampus during development. Radial glia are known to regulate hippocampal formation, but their precise function in this process is yet to be defined. We find that in Nuclear Factor I b (Nfib)-deficient mice, a subpopulation of glia from the ammonic neuroepithelium of the hippocampus fail to develop. This results in severe morphological defects, including a failure of the hippocampal fissure, and subsequently the dentate gyrus, to form. As in wild-type mice, immature nestin-positive glia, which encompass all types of radial glia, populate the hippocampus inNfib-deficient mice at embryonic day 15. However, these fail to mature into GLAST- and GFAP-positive glia, and the supragranular glial bundle is absent. In contrast, the fimbrial glial bundle forms, but alone is insufficient for proper hippocampal morphogenesis. Dentate granule neurons are present in the mutant hippocampus but their migration is aberrant, likely resulting from the lack of the complete radial glial scaffold usually provided by both glial bundles. These data demonstrate a role forNfibin hippocampal fissure and dentate gyrus formation, and that distinct glial bundles are critical for correct hippocampal morphogenesis.
Neuronal Death Resulting from Targeted Disruption of the Snf2 Protein ATRX Is Mediated by p53
Authors: Seah Claudia , Levy Michael A. , Jiang Yan , Mokhtarzada Sulayman , Higgs Douglas R. , Gibbons Richard J. , Bérubé Nathalie G.
Published: November 2008

ATRX, a chromatin remodeling protein of the Snf2 family, participates in diverse cellular functions including regulation of gene expression and chromosome alignment during mitosis and meiosis. Mutations in the human gene cause alpha thalassemia mental retardation, X-linked (ATR-X) syndrome, a rare disorder characterized by severe cognitive deficits, microcephaly and epileptic seizures. Conditional inactivation of theAtrxgene in the mouse forebrain leads to neonatal lethality and defective neurogenesis manifested by increased cell death and reduced cellularity in the developing neocortex and hippocampus. Here, we show thatAtrx-null forebrains do not generate dentate granule cells due to a reduction in precursor cell number and abnormal migration of differentiating granule cells. In addition, fewer GABA-producing interneurons are generated that migrate from the ventral telencephalon to the cortex and hippocampus. Staining for cleaved caspase 3 demonstrated increased apoptosis in both the hippocampal hem and basal telencephalon concurrent with p53 pathway activation. Elimination of the tumor suppressor protein p53 in double knock-out mice rescued cell death in the embryonic telencephalon but only partially ameliorated theAtrx-null phenotypes at birth. Together, these findings show that ATRX deficiency leads to p53-dependent neuronal apoptosis which is responsible for some but not all of the phenotypic consequences of ATRX deficiency in the forebrain.
Kalirin-7 Is Required for Synaptic Structure and Function
Authors: Ma Xin-Ming , Kiraly Drew D. , Gaier Eric D. , Wang Yanping , Kim Eun-Ji , Levine Eric S. , Eipper Betty A. , Mains Richard E.
Published: November 2008

Rho GTPases activated by GDP/GTP exchange factors (GEFs) play key roles in the developing and adult nervous system. Kalirin-7 (Kal7), the predominant adult splice form of the multifunctional Kalirin RhoGEF, includes a PDZ [postsynaptic density-95 (PSD-95)/Discs large (Dlg)/zona occludens-1 (ZO-1)] binding domain and localizes to the postsynaptic side of excitatory synapses.In vitrostudies demonstrated that overexpression of Kal7 increased dendritic spine density, whereas reduced expression of endogenous Kal7 decreased spine density. To evaluate the role of Kal7in vivo, mice lacking the terminal exon unique to Kal7 were created. Mice lacking both copies of the Kal7 exon (Kal7KO) grew and reproduced normally. Golgi impregnation and electron microscopy revealed decreased hippocampal spine density in Kal7KOmice. Behaviorally, Kal7KOmice showed decreased anxiety-like behavior in the elevated zero maze and impaired acquisition of a passive avoidance task, but normal behavior in open field, object recognition, and radial arm maze tasks. Kal7KOmice were deficient in hippocampal long-term potentiation. Western blot analysis confirmed the absence of Kal7 and revealed compensatory increases in larger Kalirin isoforms. PSDs purified from the cortices of Kal7KOmice showed a deficit in Cdk5, a kinase known to phosphorylate Kal7 and play an essential role in synaptic function. The early stages of excitatory synaptic development proceeded normally in cortical neurons prepared from Kal7KOmice, with decreased excitatory synapses apparent only after 21 d invitro. Expression of exogenous Kal7 in Kal7KOneurons rescued this deficit. Kal7 plays an essential role in synaptic structure and function, affecting a subset of cognitive processes.
Expression of Atp8b3 in murine testis and its characterization as a testis specific P-type ATPase
Authors: Gong Eun-Yeung , Park Eunsook , Lee Hyun Joo , Lee Keesook
Published: November 2008

Spermatogenesis is a complex process that produces haploid motile sperms from diploid spermatogonia through dramatic morphological and biochemical changes. P-type ATPases, which support a variety of cellular processes, have been shown to play a role in the functioning of sperm. In this study, we isolated one putative androgen-regulated gene, which is the previously reported sperm-specific aminophospholipid transporter (Atp8b3, previously known asSaplt), and explored its expression pattern in murine testis and its biochemical characteristics as a P-type ATPase.Atp8b3is exclusively expressed in the testis and its expression is developmentally regulated during testicular development. Immunohistochemistry of the testis reveals thatAtp8b3is expressed only in germ cells, especially haploid spermatids, and the protein is localized in developing acrosomes. As expected, from its primary amino acid sequence, ATP8B3 has an ATPase activity and is phosphorylated by an ATP-producing acylphosphate intermediate, which is a signature property of the P-Type ATPases. Together, ATP8B3 may play a role in acrosome development and/or in sperm function during fertilization.
Molecular characterization of egg envelope glycoprotein ZPD in the ovary of Japanese quail (Coturnix japonica)
Authors: Sato Tsukasa , Kinoshita Mihoko , Kansaku Norio , Tahara Kenichi , Tsukada Akira , Ono Hiroko , Yoshimura Takashi , Dohra Hideo , Sasanami Tomohiro
Published: November 2008

The egg envelope surrounding avian oocytes exhibits a three-dimensional network of coarse fibers between the granulosa cells and the oocyte. Our previous studies have demonstrated that one of the matrix's components, ZP3, is synthesized in the ovarian granulosa cells. Another component, ZP1, which is critically involved in triggering the sperm acrosome reaction, is synthesized in the liver. We have previously isolated cDNAs encoding quailZP3andZP1, and we now report the isolation of cDNA encoding quailZPD. By RNase protection assay andin situhybridization, we have demonstrated that ZPD transcripts are restricted to the granulosa cells of preovulatory follicles. The expression level ofZPDincreased progressively during follicular development, and the highest expression was observed in the largest follicles. Western blot analyses using the specific antibody against ZPD indicate that the 40 kDa protein is the authentic ZPD, and the contents of ZPD protein also increased during follicular development. Moreover, we found that the addition of FSH to the culture media enhances the ZPD secretion in the cultured granulosa cells. Two-dimensional gel electrophoresis revealed the presence of several ZPD isoforms with different pI values ranging from 5.5 to 7. Immunohistochemical analyses indicate that the materials recognized with anti-quail ZPD antibody were accumulated in the egg envelope of large yellow follicles. These results demonstrate the presence of ZPD protein in the egg envelope, and that the amount of ZPD in the egg envelope as well as the mRNA in the cells increases at the latter stages of folliculogenesis.
Analysis of gene transcription alterations at the blastocyst stage related to the long-term consequences of in vitro culture in mice
Authors: Fernández-González Raúl , de Dios Hourcade Juan , López-Vidriero Irene , Benguría Alberto , De Fonseca Fernando Rodríguez , Gutiérrez-Adán Alfonso
Published: November 2008

We have reported thatin vitroculture (IVC) of preimplantation mouse embryos in the presence of FCS produces long-term effects (LTE) on development, growth and behaviour of the offspring at adult age. To analyse the mechanisms underlying this phenomenon, we have examined development and global alterations in gene expression in the mouse blastocysts produced in the presence of FCS, conditions known to be suboptimal and that generate LTE. Embryos culturedin vitroin KSOM and in KSOM+FCS had a reduced number of cells in the inner cell mass at the blastocyst stage compared within vivoderived embryos; however, only culture in KSOM+FCS leads to a reduction in the number of trophoblast cells. Gene expression levels were measured by comparison among three groups of blastocysts (in vivo, IVC in KSOM and IVC in KSOM+FCS). Different patterns of gene expression and development were found between embryos culturedin vitroorin vivo. Moreover, when we compared the embryos produced in KSOM versus KSOM+FCS, we observed that the presence of FCS affected the expression of 198 genes. Metabolism, proliferation, apoptosis and morphogenetic pathways were the most common processes affected by IVC. However, the presence of FCS during IVC preferentially affected genes associated with certain molecular and biological functions related to epigenetic mechanisms. These results suggest that culture-induced alterations in transcription at the blastocyst stage related to epigenetic mechanisms provide a foundation for understanding the molecular origin at the time of preimplantation development of the long-term consequences of IVC in mammals.
Prolactin in the Afrotheria: characterization of genes encoding prolactin in elephant (Loxodonta africana), hyrax (Procavia capensis) and tenrec (Echinops telfairi)
Authors: Wallis Michael
Published: November 2008

Pituitary prolactin shows an episodic pattern of molecular evolution, with occasional short bursts of rapid change imposed on a generally rather slow evolutionary rate. In mammals, episodes of rapid change occurred in the evolution of primates, cetartiodactyls, rodents and the elephant. The bursts of rapid evolution in cetartiodactyls and rodents were followed by duplications of the prolactin gene that gave rise to large families of prolactin-related proteins including placental lactogens, while in primates the burst was followed by corresponding duplications of the related GH gene. The position in elephant is less clear. Extensive data relating to the genomic sequences of elephant and two additional members of the group Afrotheria are now available, and have been used here to characterize the prolactin genes in these species and explore whether additional prolactin-related genes are present. The results confirm the rapid evolution of elephant (Loxodonta africana) prolactin – the sequence of elephant prolactin is substantially different from that predicted for the ancestral placental mammal. Hyrax (Procavia capensis) prolactin is even more divergent but tenrec (Echinops telfairi) prolactin is strongly conserved. No evidence was obtained from searches of public databases for additional genes encoding prolactin-like proteins in any of these species. Detailed analysis of evolutionary rates, and other factors, indicates that the episode of rapid change in hyrax, and probably elephant, was adaptive, though the nature of the associated biological change(s) is not clear.
Systematic Review: Predictors of Successful Transition to Community-Based Care for Adults With Chronic Care Needs
Authors: Jacob Lolita , Poletick Eileen Blechman
Published: November 2008

Difficult transition from acute hospital back to the community can be challenging. Problems encountered during this process can lead to unplanned readmission and emergency department visits. It is important for care managers to be able to identify patients susceptible to difficult transition and to understand strategies to reduce risk of unplanned hospital readmission. This qualitative systematic review of 10 studies of discharge interventions and patient characteristics finds little evidence that enhanced discharge support is related to improved physical status at home, but there is mixed support for its role in preventing or delaying hospital readmissions in certain discharge diagnoses, specifically heart failure and stroke. Additionally, those with adequate social support and confidence in their self-care ability tend to experience fewer readmissions than do those living alone and those who perceive themselves as not ready to return home.
Measuring Case Managers’ Advance Care Planning Practice: Translating Focus Group Findings to Survey Development
Authors: Black Kathy , Fauske Janice
Published: November 2008

Sequential mixed methods is a useful research design to inform second-stage methodology when investigating an area of practice in which relatively little is known. This article describes how focus group findings were used to measure advance care planning practice among community-based case managers. The initial qualitative study utilized focus groups to explore aspects of practice in this area. Data revealed themes that embodied ambiguous views of advance care planning, divergent roles in practice, a continuum of practice activities, and multiple facilitators and barriers to practice. In order to further examine case managers’ advance care planning practices, qualitative findings were used to develop the Case Managers Advance Care Planning Practices Instrument. Implications for qualitative to quantitative measurement are discussed.
Intergenerational Transmission of Glucose Intolerance and Obesity by In Utero Undernutrition in Mice
Authors: Jimenez-Chillaron Josep C. , Isganaitis Elvira , Charalambous Marika , Gesta Stephane , Pentinat-Pelegrin Thais , Faucette Ryan R. , Otis Jessica P. , Chow Alice , Diaz Ruben , Ferguson-Smith Anne , Patti Mary-Elizabeth
Published: November 2008

OBJECTIVE—Low birth weight (LBW) is associated with increased risk of obesity, diabetes, and cardiovascular disease during adult life. Moreover, this programmed disease risk can progress to subsequent generations. We previously described a mouse model of LBW, produced by maternal caloric undernutrition (UN) during late gestation. LBW offspring (F1-UN generation) develop progressive obesity and impaired glucose tolerance (IGT) with aging. We aimed to determine whether such metabolic phenotypes can be transmitted to subsequent generations in an experimental model, even in the absence of altered nutrition during the second pregnancy.

RESEARCH DESIGN AND METHODS—We intercrossed female and male F1 adult control (C) and UN mice and characterized metabolic phenotypes in F2 offspring.

RESULTS—We demonstrate that 1) reduced birth weight progresses to F2 offspring through the paternal line (C♀-C♂ = 1.64 g; C♀-UN♂ = 1.57 g, P < 0.05; UN♀-C♂ = 1.64 g; UN♀-UN♂ = 1.60 g, P < 0.05), 2) obesity progresses through the maternal line (percent body fat: C♀-C♂ = 22.4%; C♀-UN♂ = 22.9%; UN♀-C♂ = 25.9%, P < 0.05; UN♀-UN♂ = 27.5%, P < 0.05), and 3) IGT progresses through both parental lineages (glucose tolerance test area under curve C♀-C♂ = 100; C♀-UN♂ = 122, P < 0.05; UN♀-C♂ = 131, P < 0.05; UN♀-UN♂ = 151, P < 0.05). Mechanistically, IGT in both F1 and F2 generations is linked to impaired β-cell function, explained, in part, by dysregulation of Sur1 expression.

CONCLUSIONS—Maternal undernutrition during pregnancy (F0) programs reduced birth weight, IGT, and obesity in both first- and second-generation offspring. Sex-specific transmission of phenotypes implicates complex mechanisms including alterations in the maternal metabolic environment (transmaternal inheritance of obesity), gene expression mediated by developmental and epigenetic pathways (transpaternal inheritance of LBW), or both (IGT).
Enhanced Expression of Janus Kinase–Signal Transducer and Activator of Transcription Pathway Members in Human Diabetic Nephropathy
Authors: Berthier Celine C. , Zhang Hongyu , Schin MaryLee , Henger Anna , Nelson Robert G. , Yee Berne , Boucherot Anissa , Neusser Matthias A. , Cohen Clemens D. , Carter-Su Christin , Argetsinger Lawrence S. , Rastaldi Maria P. , Brosius Frank C. , Kretzler Matthias
Published: November 2008

OBJECTIVE—Glomerular mesangial expansion and podocyte loss are important early features of diabetic nephropathy, whereas tubulointerstitial injury and fibrosis are critical for progression of diabetic nephropathy to kidney failure. Therefore, we analyzed the expression of genes in glomeruli and tubulointerstitium in kidney biopsies from diabetic nephropathy patients to identify pathways that may be activated in humans but not in murine models of diabetic nephropathy that fail to progress to glomerulosclerosis, tubulointerstitial fibrosis, and kidney failure.

RESEARCH DESIGN AND METHODS—Kidney biopsies were obtained from 74 patients (control subjects, early and progressive type 2 diabetic nephropathy). Glomerular and tubulointerstitial mRNAs were microarrayed, followed by bioinformatics analyses. Gene expression changes were confirmed by real-time RT-PCR and immunohistological staining. Samples from db/db C57BLKS and streptozotocin-induced DBA/2J mice, commonly studied murine models of diabetic nephropathy, were analyzed.

RESULTS—In human glomeruli and tubulointerstitial samples, the Janus kinase (Jak)-signal transducer and activator of transcription (Stat) pathway was highly and significantly regulated. Jak-1, -2, and -3 as well as Stat-1 and -3 were expressed at higher levels in patients with diabetic nephropathy than in control subjects. The estimated glomerular filtration rate significantly correlated with tubulointerstitial Jak-1, -2, and -3 and Stat-1 expression (R2 = 0.30–0.44). Immunohistochemistry found strong Jak-2 staining in glomerular and tubulointerstitial compartments in diabetic nephropathy compared with control subjects. In contrast, there was little or no increase in expression of Jak/Stat genes in the db/db C57BLKS or diabetic DBA/2J mice.

CONCLUSIONS—These data suggest a direct relationship between tubulointerstitial Jak/Stat expression and progression of kidney failure in patients with type 2 diabetic nephropathy and distinguish progressive human diabetic nephropathy from nonprogressive murine diabetic nephropathy.
Effect of Age of Infusion Site and Type of Rapid-Acting Analog on Pharmacodynamic Parameters of Insulin Boluses in Youth With Type 1 Diabetes Receiving Insulin Pump Therapy
Authors: Swan Karena L. , Dziura James D. , Steil Garry M. , Voskanyan Gayane R. , Sikes Kristin A. , Steffen Amy T. , Martin Melody L. , Tamborlane William V. , Weinzimer Stuart A.
Published: November 2008

OBJECTIVE—The purpose of this study was to examine the effect of type of insulin analog and age of insertion site on the pharmacodynamic characteristics of a standard insulin bolus in youth with type 1 diabetes receiving insulin pump therapy.

RESEARCH DESIGN AND METHODS—Seventeen insulin pump–treated adolescents with type 1 diabetes underwent two euglycemic clamp procedures after a 0.2 unit/kg bolus of either insulin aspart or lispro on day 1 and day 4 of insulin pump site insertion. The glucose infusion rate (GIR) required to maintain euglycemia was the primary pharmacodynamic measure.

RESULTS—There were no statistically significant differences in any of the pharmacodynamic parameters between aspart and lispro during day 1 and day 4. However, when the two groups were combined, time to discontinuation of exogenous glucose infusion, and time to half-maximal onset and offset of insulin action were observed significantly earlier during day 4 compared with day 1 (P = 0.03–0.0004), but the overall area under the GIR curve was similar on day 1 and day 4.

CONCLUSIONS—With both insulin aspart and lispro, there is an earlier peak and shorter duration of action with increasing duration of infusion site use, but overall insulin action is not affected.
Effects of an Intravenous Lipid Challenge and Free Fatty Acid Elevation on In Vivo Insulin Sensitivity in African American Versus Caucasian Adolescents
Authors: Burns Stephen F. , Kelsey Sheryl F. , Arslanian Silva A.
Published: November 2008

OBJECTIVE—African American youth have lower insulin sensitivity than their Caucasian peers, but the metabolic pathways responsible for this difference remain unknown. Free fatty acids (FFAs) are associated with insulin resistance through the Randle cycle. The present investigation determined whether elevating FFA is more deleterious to insulin sensitivity in African American than in Caucasian adolescents.

RESEARCH DESIGN AND METHODS—Insulin sensitivity (3-h hyperinsulinemic-euglycemic clamp) was evaluated in 22 African American and 21 Caucasian adolescents on two occasions: 1) infusion of normal saline and 2) infusion of 20% intralipid.

RESULTS—During intralipid infusion, fasting insulin and C-peptide concentrations increased while fasting glucose and basal glucose turnover did not change in either group. Insulin sensitivity decreased similarly in African American (normal saline 7.65 ± 0.61 vs. intralipid 5.15 ± 0.52 μmol · kg−1 · min−1 per pmol/l) and Caucasian subjects (normal saline 8.97 ± 0.85 vs. intralipid 5.96 ± 0.56 μmol · kg−1 · min−1 per pmol/l) (P < 0.001).

CONCLUSIONS—African American and Caucasian adolescents respond to FFA elevation similarly through increased fasting insulin secretion to maintain fasting glucose homeostasis and reduced peripheral glucose uptake and insulin resistance. Thus, African American adolescents are not more susceptible to FFA-induced insulin resistance than Caucasian youth.
Fasting Plasma C-Peptide and Micro- and Macrovascular Complications in a Large Clinic-Based Cohort of Type 1 Diabetic Patients
Authors: Panero Francesco , Novelli Giulia , Zucco Chiara , Fornengo Paolo , Perotto Massimo , Segre Olivia , Grassi Giorgio , Cavallo-Perin Paolo , Bruno Graziella
Published: November 2008

OBJECTIVE—A protective effect of residual β-cell function on microvascular complications of type 1 diabetes has been suggested. Our aim was to retrospectively evaluate the association of fasting plasma C-peptide values with micro- and macrovascular complications.

RESEARCH DESIGN AND METHODS—We recruited a clinic-based cohort of 471 type 1 diabetic patients born after 1945 and cared for in the period 1994–2004. Centralized measurements and standardized procedures of ascertainment of micro- and macrovascular complications were employed. Individual cumulative averages of A1C up to 2007 were calculated.

RESULTS—Residual β-cell secretion was detected even many years after diabetes diagnosis. In multivariate linear regression analysis, fasting plasma C-peptide values were positively associated with age at diagnosis (β = 0.02; P < 0.0001) and triglycerides (β = 0.20; P = 0.05) and inversely associated with diabetes duration (β = −0.03; P < 0.0001) and HDL cholesterol (β = −0.006; P = 0.03). The final model explained 21% of fasting C-peptide variability. With respect to fasting C-peptide values in the lowest tertile (<0.06 nmol/l), higher values were associated with lower prevalence of microvascular complications (odds ratio [OR] 0.59 [95% CI 0.37–0.94]) independently of age, sex, diabetes duration, individual cumulative A1C average during the study period, hypertension, and cardiovascular diseases. No association was evident with macrovascular complications (0.77 [0.38–1.58]).

CONCLUSIONS—Our study shows an independent protective effect of residual β-cell function on the development of microvascular complications in type 1 diabetes, suggesting the potential beneficial effect of treatment that allows the preservation of even modest β-cell function over time.
Egg Consumption and Risk of Type 2 Diabetes in Men and Women
Authors: Djoussé Luc , Gaziano J. Michael , Buring Julie E. , Lee I-Min
Published: November 2008

OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts.

RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes.

RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001).

CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.
Full Accounting of Diabetes and Pre-Diabetes in the U.S. Population in 1988–1994 and 2005–2006
Authors: Cowie Catherine C. , Rust Keith F. , Ford Earl S. , Eberhardt Mark S. , Byrd-Holt Danita D. , Li Chaoyang , Williams Desmond E. , Gregg Edward W. , Bainbridge Kathleen E. , Saydah Sharon H. , Geiss Linda S.
Published: November 2008

OBJECTIVE—We examined the prevalences of diagnosed diabetes, and undiagnosed diabetes and pre-diabetes using fasting and 2-h oral glucose tolerance test values, in the U.S. during 2005–2006. We then compared the prevalences of these conditions with those in 1988–1994.

RESEARCH DESIGN AND METHODS—In 2005–2006, the National Health and Nutrition Examination Survey included a probability sample of 7,267 people aged ≥12 years. Participants were classified according to glycemic status by interview for diagnosed diabetes and by fasting and 2-h glucoses measured in subsamples.

RESULTS—In 2005–2006, the crude prevalence of total diabetes in people aged ≥20 years was 12.9%, of which ∼40% was undiagnosed. In people aged ≥20 years, the crude prevalence of impaired fasting glucose was 25.7% and of impaired glucose tolerance was 13.8%, with almost 30% having either. Over 40% of individuals had diabetes or pre-diabetes. Almost one-third of the elderly had diabetes, and three-quarters had diabetes or pre-diabetes. Compared with non-Hispanic whites, age- and sex-standardized prevalence of diagnosed diabetes was approximately twice as high in non-Hispanic blacks (P < 0.0001) and Mexican Americans (P = 0.0001), whereas undiagnosed diabetes was not higher. Crude prevalence of diagnosed diabetes in people aged ≥20 years rose from 5.1% in 1988–1994 to 7.7% in 2005–2006 (P = 0.0001); this was significant after accounting for differences in age and sex, particularly in non-Hispanic blacks. Prevalences of undiagnosed diabetes and pre-diabetes were generally stable, although the proportion of total diabetes that was undiagnosed decreased in Mexican Americans.

CONCLUSIONS—Over 40% of people aged ≥20 years have hyperglycemic conditions, and prevalence is higher in minorities. Diagnosed diabetes has increased over time, but other conditions have been relatively stable.
Racial/Ethnic Differences in Concerns About Current and Future Medications Among Patients With Type 2 Diabetes
Authors: Huang Elbert S. , Brown Sydney E.S. , Thakur Nidhi , Carlisle Lisabeth , Foley Edward , Ewigman Bernard , Meltzer David O.
Published: November 2008

OBJECTIVE—To evaluate ethnic differences in medication concerns (e.g., side effects and costs) that may contribute to ethnic differences in the adoption of and adherence to type 2 diabetes treatments.

RESEARCH DESIGN AND METHODS—We conducted face-to-face interviews from May 2004 to May 2006 with type 2 diabetic patients ≥18 years of age (N = 676; 25% Latino, 34% non-Hispanic Caucasian, and 41% non-Hispanic African American) attending Chicago-area clinics. Primary outcomes of interest were concerns regarding medications and willingness to take additional medications.

RESULTS—Latinos and African Americans had higher A1C levels than Caucasians (7.69 and 7.54% vs. 7.18%, respectively; P < 0.01). Latinos and African Americans were more likely than Caucasians to worry about drug side effects (66 and 49% vs. 39%, respectively) and medication dependency (65 and 52% vs. 39%, respectively; both P < 0.01). Ethnic minorities were also more likely to report reluctance to adding medications to their regimen (Latino 12%, African American 18%, and Caucasian 7%; P < 0.01). In analyses adjusted for demographics, income, education, and diabetes duration, current report of pain/discomfort with pills (odds ratio 2.43 [95% CI 1.39–4.27]), concern regarding disruption of daily routine (1.97 [1.14–3.42]), and African American ethnicity (2.48 [1.32–4.69]) emerged as major predictors of expressed reluctance to adding medications.

CONCLUSIONS—Latinos and African Americans had significantly more concerns regarding the quality-of-life effects of diabetes-related medications than Caucasians. Whether these medication concerns contribute significantly to differences in treatment adoption and disparities in care deserves further exploration.
Erratum to “On homological classification of pomonoids by regular weak injectivity properties of S-posets”
Authors: Zhang Xia , Laan Valdis
Published: November 2008

The original version of the article was published in Central European Journal of Mathematics, 2007, 5(1), 181–200, DOI: 10.2478/s11533-006-0036-3. Unfortunately, the original version of this article contains a mistake: in Theorem 5.2 only conditions (i) and (ii) (and not (iii)) are equivalent. We correct the theorem and its proof.
Solvent-free synthesis and properties of carboxymethyl starch fatty acid ester derivatives
Authors: Mazíková Viera , Sroková Iva , Ebringerová Anna
Published: November 2008

Water-soluble, partially hydrophobized polysaccharides have become attractive due to their potential to act as polymeric surfactants. From carboxymethyl starch (CMS), water-soluble polymeric surfactants were prepared by esterification using two unconvential methods based on (A) a reaction with mixed anhydrides and (B) with methyl laureate (MELA) and methyl esters of the fatty acid complex of rape seed oil (MERO) under ‘solvent-free’ conditions. The obtained CMS derivatives were characterized by structural, surface-active and surfactant performance properties. Esterification using method B was successful in contrast to method A which yielded derivatives with a very low extent of esterification. Although the derivatives reduced the surface tension moderately, they exhibited remarkable emulsifying properties. The performance tests indicated good washing power and antiredeposition efficiency. The results suggest that suitable polymeric surfactants can be prepared by the unconventional esterification method B using both acylation agents. The preparations might substitute the expensive and invasive industrially applied conventional methods.
Simultaneous determination of 118 pesticide residues in Chinese teas by gas chromatography-mass spectrometry
Authors: Yang Xin , Xu De , Qiu Jian , Zhang Hua , Zhang Ying , Dong Ai , Ma Ying , Wang Jing
Published: November 2008

An efficient and sensitive method for simultaneous determination of 118 pesticide residues in teas has been established and validated. A multi-residue analysis of pesticides in tea involved extraction with ethyl acetate-hexane, clean-up using gel permeation chromatography (GPC) and solidphase extraction (SPE), and subsequent identification and quantification of the selected pesticides by gas chromatography-mass spectrometry (GC-MS). For most of the target analytes, optimized pretreatment processes led to no significant interference with analysis of sample matrix, and the determination of 118 compounds was achieved in about 60 min. In the linear range of each pesticide, the correlation coefficient was R 2 ≥ 0.99. At the low, medium and high three fortification levels of 0.05–2.5 mg kg−1, 118 pesticides average recoveries range from 61 % to 121 % and relative standard deviations (RSD) were in the range of 0.6–9.2 % for all analytes. The limits of detection for the method were 0.00030-0.36 mg kg−1, depending on each pesticide.
Modifications of spectrophotometric methods for total phosphorus determination in meat samples
Authors: Jastrzębska Aneta
Published: November 2008

Spectrophotometric determination of total phosphorus in meat samples was modified using the molybdenum blue reaction with the following reducing agents: ascorbic acid (AA), hydrazine sulphate (HS), and mixture of hydroquinone and hydrazine sulphate (HHS). Proposed methods were validated by evaluation of statistical parameters such as: linearity, sensitivity, limits of detection (DL) and quantification (QL), precision, and accuracy, against the standard and malachite green (MG) modified procedures and by applying food certified materials. The values of within-day and between-days precision in meat samples for all tested reducing agents were better than 3.4 % and 4.2 %, respectively. The recoveries for CRMs analyses were between 92 % and 102.3 %. Obtained results suggest usefulness of the hydroquinone and hydrazine sulphate mixture in the determination of phosphorus ions.
Status of maternal health in Nepal
Authors: Vaidya Achala
Published: November 2008

doi:10.3126/njog.v2i1.1466 N. J. Obstet. Gynaecol Vol. 2, No. 1, p. 1 - 3 May -June 2007
Obstetric performance in elderly Nigerian women: A comparative study
Authors: Ezechi OC , Kalu BKE , Loto OM , Ezeobi PM , Nwokoro CA
Published: November 2008

Aims: To study the obstetric outcome in Nigerian women aged 35 years and above while comparing them with younger women matched for parity, socioeconomic class and body mass index. Method: A cohort of 132 pregnant women aged 35 years and above with another 269 pregnant women aged 20-25 years matched for parity, socioeconomic class and body mass index seen at the obstetric unit of a multidisciplinary proprietary hospital in Lagos Nigeria. Results: There were statistically significant difference between the two group in incidence of chronic hypertension (P = 0.02), gestational diabetes (P = 0.05), symptomatic fibroid (P = 0.01), frequent hospitalisation (P = 0.007), caesarean section (P = 0.005), operative vaginal delivery (P = 0.042), Induction of labour (P = 0.024) premature delivery (P = 0.001), low birth weight (P = 0.021) and congenital abnormality but not in Preeclampsia, malpresentation, obstetric haemorrhage, wound infection and multiple pregnancy . Conclusion: This study demonstrated that women at 35 years and above are high-risk group and should be closely supervised during pregnancy. Keywords: Elderly, Nigerians, obstetric performance   doi:10.3126/njog.v2i1.1468 N. J. Obstet. Gynaecol Vol. 2, No. 1, p. 9 - 12 May -June 2007
Active management of third stage of labour by oxytocin: Umbilical vein versus intramuscular use
Authors: Ojha Neebha , Malla Dibya S
Published: November 2008

Aim: To compare oxytocin used via intraumbilical or intramuscular route in the active management of third stage of labour with respect to duration and amount of bleeding. Methods: Prospective comparative study conducted in Maternity Hospital, Thapathali, Kathmandu for three months 29th April - July 28th 2004 (061/1/16 to 061/4/12 BS ). After immediate umbilical cord clamping following vaginal delivery, 120 women were divided into 2 groups administering 10 units of oxytocin; in Group I: which was diluted mixing with 10 ml of normal saline before it was infused intraumbilical and Group II: injected intramuscularly. Results: There was no difference in the duration of third stage of labour (3.6 vs. 3.7min) between the two groups. There was significant blood loss in the intraumblical group as compared to intramuscular group (242ml vs.168ml, p. 0.004). The need for additional oxytocic to control the uterine bleeding was more in intraumbilical group as compared to intramuscular group (28.3% vs 6.7%, p 0.005). There was more postpartum haemorrhage (PPH) in intraumbilical group (8.3% vs 3.3%, p 0.439). The injection delivery interval was significantly longer in the intraumbilical group as compared to intramuscular group (46.9 vs. 30.7 sec). Conclusion: Intraumbilical oxytocin is technically more difficult to administer without having any added benefit either in decreasing the duration of third stage of labour or reducing the blood loss. Key words: Intraumbilical oxytocin, intramuscular oxytocin, third stage of labour. doi:10.3126/njog.v2i1.1469 N. J. Obstet. Gynaecol Vol. 2, No. 1, p. 13 - 16 May -June 2007