bluuebunny/crossref_metadata_2025 huggingface dataset:
Survivin is not required for the endomitotic cell cycle of megakaryocytes
Authors: Wen Qiang , Leung Cindy , Huang Zan , Small Sara , Reddi Alagarsamy Lakku , Licht Jonathan D. , Crispino John D.
Published: April 2009

Survivin is a member of the chromosome passenger complex, which plays an important role in chromosome alignment, separation, and cytokinesis. Although survivin is required for the proliferation and survival of hematopoietic stem and progenitor cells, the extent to which it is necessary for endomitosis of megakaryocytes remains controversial. To determine whether survivin is required for polyploidization, we analyzed mice with a megakaryocyte-specific deletion. PF4-Cre/survivinfl/fl mice harbored normal platelet counts with megakaryocytes that reached ploidy states comparable with those of control littermates. The CD41+ cells within these animals showed little excision but increased annexin V staining, implying that survivin is required for survival of megakaryocyte progenitors in vivo. In contrast, megakaryocytes in which survivin was excised ex vivo showed robust excision and an increased degree of polyploidization. These results demonstrate that survivin is necessary for survival of megakaryocyte progenitors, but is not required for polyploidization of committed megakaryocytes.
Clinical usefulness of the screen for cognitive impairment in psychiatry (SCIP-S) scale in patients with type I bipolar disorder
Authors: Guilera Georgina , Pino Oscar , Gómez-Benito Juana , Rojo J Emilio , Vieta Eduard , Tabarés-Seisdedos Rafael , Segarra Nuria , Martínez-Arán Anabel , Franco Manuel , Cuesta Manuel J , Crespo-Facorro Benedicto , Bernardo Miguel , Purdon Scot E , Díez Teresa , Rejas Javier ,   the Spanish Working Group in Cognitive Function
Published: April 2009

Background

The relevance of persistent cognitive deficits to the pathogenesis and prognosis of bipolar disorders (BD) is understudied, and its translation into clinical practice has been limited by the absence of brief methods assessing cognitive status in Psychiatry. This investigation assessed the psychometric properties of the Spanish version of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) for the detection of cognitive impairment in BD.

Methods

After short training, psychiatrists at 40 outpatient clinics administered the SCIP three times over two weeks to a total of 76 consecutive type I BD admissions. Experienced psychologists also administered a comprehensive battery of standard neuropsychological instruments to clinical sample and 45 healthy control subjects.

Results

Feasibility was supported by a brief administration time (approximately 15 minutes) and minimal scoring errors. The reliability of the SCIP was confirmed by good equivalence of forms, acceptable stability (ICC range 0.59 to 0.87) and adequate internal consistency (Chronbach's alpha of 0.74). Construct validity was granted by extraction of a single factor (accounting 52% of the variance), acceptable correlations with conventional neuropsychological instruments, and a clear differentiation between bipolar I and normal samples. Efficiency was also provided by the adequate sensitivity and specificity.

Limitations

The sample size is not very large. The SCIP and the neurocognitive battery do not cover all potentially relevant cognitive domains. Also, sensitivity to change remains unexplored.

Conclusion

With minimal training, physicians obtained a reliable and valid estimate of cognitive impairment in approximately 15 minutes from an application of the SCIP to type I BD patients.
The Action Gambler and Equal-Sized Wagering
Authors: Hartvigsen David
Published: April 2009

A gambler with an initial bankroll is faced with a finite sequence of identical and independent bets. For each bet, he may wager up to his current bankroll, and will win this amount with probability p or lose it with probability 1-p. His problem is to devise a wagering strategy that will maximize his final expected utility with the side condition that the total amount wagered (i.e. the total ‘action’) be at least his initial bankroll. Our main result is an expression that characterizes when the strategy of placing equal-sized wagers on all bets is optimal. In particular, for a given bankroll B, utility function f (concave, increasing, differentiable), and n bets, we show that it is optimal to wager b/n on each bet if and only if the probability of winning each bet is less than or equal to some value p⋆∈[½,1] (where p⋆ is an explicit function of B, f, and n). We prove the result by using a basic nonlinear programming technique.
Activity of the AMPA receptor regulates drebrin stabilization in dendritic spine morphogenesis
Authors: Takahashi Hideto , Yamazaki Hiroyuki , Hanamura Kenji , Sekino Yuko , Shirao Tomoaki
Published: April 2009

Spine morphogenesis mainly occurs during development as a morphological shift from filopodia-like thin protrusions to bulbous ones. We have previously reported that synaptic clustering of the actin-binding protein drebrin in dendritic filopodia governs spine morphogenesis and synaptic PSD-95 clustering. Here, we report the activity-dependent cellular mechanisms for spine morphogenesis, in which the activity of AMPA receptors (AMPARs) regulates drebrin clustering in spines by promoting drebrin stabilization. In cultured developing hippocampal neurons, pharmacological blockade of AMPARs, but not of other glutamate receptors, suppressed postsynaptic drebrin clustering without affecting presynaptic clustering of synapsin I (synapsin-1). Conversely, the enhancement of the action of AMPARs promoted drebrin clustering in spines. When we explored drebrin dynamics by photobleaching individual spines, we found that AMPAR activity increased the fraction of stable drebrin without affecting the time constant of drebrin turnover. An increase in the fraction of stable drebrin corresponded with increased drebrin clustering. AMPAR blockade also suppressed normal morphological maturation of spines and synaptic PSD-95 clustering in spines. Together, these data suggest that AMPAR-mediated stabilization of drebrin in spines is an activity-dependent cellular mechanism for spine morphogenesis.
Fatal Liver Failure in a Patient on Acetaminophen Treated with Sunitinib Malate and Levothyroxine
Authors: Weise Amy M , Liu Chin Y , Shields Anthony F
Published: April 2009

Objective:

To report the occurrence of fatal acute liver failure following addition of levothyroxine to a regimen of sunitinib and acetaminophen.

Case Summary:

A 57-year-old woman who started sunitinib treatment for relapsed metastatic gastrointestinal stromal tumor after imatinib failure had disease stabilization and normal livar function through 8 cycles of sunitinib 50 mg/day for 4 weeks, followed by 2 weeks off treatment. Her continuing medications included acetaminophen approximately 4.5 g/wk, as well as standard medications for asthma. In cycle 8, she received oral levothyroxine 50–150 pg/day for approximately 30 days to control hypothyroidism before beginning cycle 9 of sunitinib. On day 4 of cycle 9, she was hospitalized with progressively rising circulating liver enzyme levels. She died 4 days postadmission despite discontinuation of sunitinib and initiation of Intensive supportive treatment. At autopsy, her liver showed severe centrliobular necrosis with moderate-to-severe steatosis and minimal parenchymal invasion by the neoplasm. Viral stains were negative.

Discussion:

Hepatic failure has been reported rarely in patients receiving sunitinib. Autopsy results excluded neoplastic disease progression and viral infection in the etiology of the event, and the patient may have died of the combined interaction of sunitinib, acetaminophen, and levothyroxine. Although sunitinib was not more than a possible hepatotoxin (Roussel Uclaf Causality Assessment Method) and may even have been hepatoprotective over a 48-week period against chronic intake of acetaminophen (probable hepatotoxin) by producing regional hypothyroidism within the liver, it is hypothesized that correction of the putative hepatic hypothyroidism with oral levothyroxine (possible hepatotoxin) and reinitiation of sunitinib treatment may have triggered hepatic necrosis.

Conclusions:

Acetaminophen should be used with particular caution in patients receiving sunitinib. In sunitinib-treated patients who also require levothyroxine therapy, increased caution in restarting subsequent sunitinib treatment and discontinuation of acetaminophen, if possible, is advisable. Further evaluation of this potential interaction is warranted.
Treatment of Osteoporosis/Osteopenia in Pediatric Leukemia and Lymphoma
Authors: Bryant Michele L , Worthington Mary A , Parsons Kerry
Published: April 2009

Objective:

To evaluate the efficacy and safety of various treatment options for osteopenia and osteoporosis secondary to cancer treatment in pediatric patients undergoing cancer therapy.

Data Sources:

A systematic search of PubMed (1949–November 2008) and international Pharmaceutical Abstracts (to November 2008) was conducted using the following search terms: osteoporosis, osteopenia, pediatrics, cancer, neoplasms, chemotherapy, bisphosphonates, calcium, vitamin D, calcitonin, and physical therapy.

Study Selection and Data Extraction:

All prospective studies that evaluated various osteoporosis treatment options in pediatric patients undergoing chemotherapy were included. Results from studies evaluating bisphosphonates and other treatments in children with osteoporosis due to other causes were also included if important safety and efficacy data were provided. Most commonly reported primary efficacy endpoints included comparisons of bone density parameters measured before and after treatment.

Data Synthesis:

Four clinical studies and 2 case reports describing treatment with bisphosphonates, specifically alendronate and Pamidronate, for osteoporosis or osteopenia in pediatric cancer patients were identified. Results from the trials showed that these medications were efficacious in reducing bone mineral density loss during cancer therapy and were well tolerated in this special population. Primary efficacy endpoints included improvements in Z-scores measured by dual-energy X-ray absorptiometry scans. The most commonly reported adverse effects included hypocalcemia, mild stomach upset, and infusion-related hyperpyrexia. Four additional clinical trials involving the treatment of osteoporosis or osteopenia in children and adolescents who developed bone degeneration after chronic steroid therapy are also included. In these trials, treatment options such as calcitonin, and calcium and vitamin D supplementation were also shown to be beneficial.

Conclusions:

The clinical trials published to date are limited to only a few conducted in small populations of patients diagnosed with lymphoblastic leukemia or non–Hodgkin's lymphoma. However, alendronate and Pamidronate both appeared to be effective options in improving bone mineral density scores with minimal adverse effects.
Book Reviews
Authors: Teucher Ulrich
Published: April 2009

Swimming in a Sea of Death: A Son's Memoir By David Rieff New York, NY: Simon & Schuster, 2008. pp. 180, Hardcover $21.00, ISBN: 978‐0‐7432‐9946‐6, 0‐7432‐9946‐9
A SnoN–Ccd1 Pathway Promotes Axonal Morphogenesis in the Mammalian Brain
Authors: Ikeuchi Yoshiho , Stegmüller Judith , Netherton Stuart , Huynh Mai Anh , Masu Masayuki , Frank David , Bonni Shirin , Bonni Azad
Published: April 2009

The transcriptional corepressor SnoN is a critical regulator of axonal morphogenesis, but how SnoN drives axonal growth is unknown. Here, we report that gene-profiling analyses in cerebellar granule neurons reveal that the large majority of genes altered upon SnoN knockdown are surprisingly downregulated, suggesting that SnoN may activate transcription in neurons. Accordingly, we find that the transcriptional coactivator p300 interacts with SnoN, and p300 plays a critical role in SnoN-induced axon growth. We also identify the gene encoding the signaling scaffold protein Ccd1 as a critical target of SnoN in neurons. Ccd1 localizes to the actin cytoskeleton, is enriched at axon terminals in neurons, and activates the axon growth-promoting kinase JNK (c-Jun N-terminal protein kinase). Knockdown of Ccd1 in neurons reduces axonal length and suppresses the ability of SnoN to promote axonal growth. Importantly, Ccd1 knockdown in rat pups profoundly impairs the formation of granule neuron parallel fiber axons in the rat cerebellar cortexin vivo. These findings define a novel SnoN–Ccd1 link that promotes axonal growth in the mammalian brain, with important implications for axonal development and regeneration.
Anatomical Characterization of Human Fetal Brain Development with Diffusion Tensor Magnetic Resonance Imaging
Authors: Huang Hao , Xue Rong , Zhang Jiangyang , Ren Tianbo , Richards Linda J. , Yarowsky Paul , Miller Michael I. , Mori Susumu
Published: April 2009

The human brain is extraordinarily complex, and yet its origin is a simple tubular structure. Characterizing its anatomy at different stages of human fetal brain development not only aids in understanding this highly ordered process but also provides clues to detecting abnormalities caused by genetic or environmental factors. During the second trimester of human fetal development, neural structures in the brain undergo significant morphological changes. Diffusion tensor imaging (DTI), a novel method of magnetic resonance imaging, is capable of delineating anatomical components with high contrast and revealing structures at the microscopic level. In this study, high-resolution and high-signal-to-noise-ratio DTI data of fixed tissues of second-trimester human fetal brains were acquired and analyzed. DTI color maps and tractography revealed that important white matter tracts, such as the corpus callosum and uncinate and inferior longitudinal fasciculi, become apparent during this period. Three-dimensional reconstruction shows that major brain fissures appear while most of the cerebral surface remains smooth until the end of the second trimester. A dominant radial organization was identified at 15 gestational weeks, followed by both laminar and radial architectures in the cerebral wall throughout the remainder of the second trimester. Volumetric measurements of different structures indicate that the volumes of basal ganglia and ganglionic eminence increase along with that of the whole brain, while the ventricle size decreases in the later second trimester. The developing fetal brain DTI database presented can be used for education, as an anatomical research reference, and for data registration.
JNK-Induced MCP-1 Production in Spinal Cord Astrocytes Contributes to Central Sensitization and Neuropathic Pain
Authors: Gao Yong-Jing , Zhang Ling , Samad Omar Abdel , Suter Marc R. , Yasuhiko Kawasaki , Xu Zhen-Zhong , Park Jong-Yeon , Lind Anne-Li , Ma Qiufu , Ji Ru-Rong
Published: April 2009

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor α (TNF-α) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-α/JNK pathway. MCP-1 upregulation by TNF-α was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-α produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.
Resting Microglia Directly Monitor the Functional State of SynapsesIn Vivoand Determine the Fate of Ischemic Terminals
Authors: Wake Hiroaki , Moorhouse Andrew J. , Jinno Shozo , Kohsaka Shinichi , Nabekura Junichi
Published: April 2009

Recent studies have identified the important contribution of glial cells to the plasticity of neuronal circuits. Resting microglia, the primary immune effector cells in the brain, dynamically extend and retract their processes as if actively surveying the microenvironment. However, just what is being sampled by these resting microglial processes has not been demonstratedin vivo, and the nature and function of any interactions between microglia and neuronal circuits is incompletely understood. Usingin vivotwo-photon imaging of fluorescent-labeled neurons and microglia, we demonstrate that the resting microglial processes make brief (∼5 min) and direct contacts with neuronal synapses at a frequency of about once per hour. These contacts are activity-dependent, being reduced in frequency by reductions in neuronal activity. After transient cerebral ischemia, the duration of these microglia–synapse contacts are markedly prolonged (∼1 h) and are frequently followed by the disappearance of the presynaptic bouton. Our results demonstrate that at least part of the dynamic motility of resting microglial processesin vivois directed toward synapses and propose that microglia vigilantly monitor and respond to the functional status of synapses. Furthermore, the striking finding that some synapses in the ischemic areas disappear after prolonged microglial contact suggests microglia contribute to the subsequent increased turnover of synaptic connections. Further understanding of the mechanisms involved in the microglial detection of the functional state of synapses, and of their role in remodeling neuronal circuits disrupted by ischemia, may lead to novel therapies for treating brain injury that target microglia.
Neuropeptide S Reinstates Cocaine-Seeking Behavior and Increases Locomotor Activity through Corticotropin-Releasing Factor Receptor 1 in Mice
Authors: Pañeda Covadonga , Huitron-Resendiz Salvador , Frago Laura M. , Chowen Julie A. , Picetti Roberto , Lecea Luis de , Roberts Amanda J.
Published: April 2009

Neuropeptide S (NPS) is a recently discovered neuropeptide that increases arousal and wakefulness while decreasing anxiety-like behavior. Here, we used a self-administration paradigm to demonstrate that intracerebroventricular infusion of NPS reinstates extinguished cocaine-seeking behavior in a dose-dependent manner in mice. The highest dose of NPS (0.45 nm) increased active lever pressing in the absence of cocaine to levels that were equivalent to those observed during self-administration. In addition, we examined the role of the corticotropin-releasing factor receptor 1 (CRF1) in this behavior as well as locomotor stimulation and anxiolysis. CRF1knock-out mice did not respond to either the locomotor stimulant or cocaine reinstatement effects of NPS, but still responded to its anxiolytic effect. The CRF1antagonist antalarmin also blocked the increase in active lever responding in the reinstatement model and the locomotor activating properties of NPS without affecting its anxiolytic actions. Our results suggest that NPS receptors may be an important target for drug abuse research and treatment and that CRF1mediates the cocaine-seeking and locomotor stimulant effects of NPS, but not its effects on anxiety-like behavior.
A Role for Synaptic Zinc in Activity-Dependent Aβ Oligomer Formation and Accumulation at Excitatory Synapses
Authors: Deshpande Atul , Kawai Hideki , Metherate Raju , Glabe Charles G. , Busciglio Jorge
Published: April 2009

Soluble amyloid β oligomers (AβOs) interfere with synaptic function and bind with high affinity to synapses, but the mechanism underlying AβO synaptic targeting is not known. Here, we show that the accumulation of synthetic or native Alzheimer's disease (AD)-brain oligomers at synapses is regulated by synaptic activity. Electrical or chemical stimulation increased AβO synaptic localization and enhanced oligomer formation at synaptic terminals, whereas inhibition with TTX blocked AβO synaptic localization and reduced AβO synaptic load. The zinc-binding 8-OH-quinoline clioquinol markedly reduced AβO synaptic targeting, which was also reduced in brain sections of animals deficient in the synaptic vesicle zinc transporter ZnT3, indicating that vesicular zinc released during neurotransmission is critical for AβO synaptic targeting. Oligomers were not internalized in recycled vesicles but remained at the cell surface, where they colocalized with NR2B NMDA receptor subunits. Furthermore, NMDA antagonists blocked AβO synaptic targeting, implicating excitatory receptor activity in oligomer formation and accumulation at synapses. In AD brains, oligomers of different size colocalized with synaptic markers in hippocampus and cortex, where oligomer synaptic accumulation correlated with synaptic loss.
Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4α
Authors: Selva David M , Hammond Geoffrey L
Published: April 2009

Thyroid hormones increase hepatic sex hormone-binding globulin (SHBG) production, which is also regulated by hepatocyte nuclear factor-4α (HNF-4α) in response to changes in the metabolic state of the liver. Since the human SHBG promoter lacks a typical thyroid hormone response element, and because thyroid hormones influence metabolic state, we set out to determine whether thyroid hormones mediate SHBG expression indirectly via changes in HNF-4α levels in HepG2 human hepatoblastoma cells, and in the livers of transgenic mice that express a 4.3 kb human SHBG transgene under the control of its own 0.8 kb promoter sequence. Thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) increase SHBG accumulation in HepG2 cell culture medium over 5 days, and increase cellular SHBG mRNA levels. In addition, T4 treatment of HepG2 cells for 5 days increased HNF-4α mRNA and HNF-4α levels in concert with decreased cellular palmitate levels. Plasma SHBG levels were also increased in mice expressing a human SHBG transgene after 5 days treatment with T3 along with increased hepatic HNF-4α levels. In HepG2 cells, the human SHBG promoter failed to respond acutely (within 24 h) to T4 treatment, but a 4-day pre-treatment with T4 resulted in a robust response that was prevented by co-treatment with HNF-4α siRNA, or by blocking the β-oxidation of palmitate through co-treatment with the carnitine palmitoyltransferase I inhibitor, etomoxir. These data lead us to conclude that thyroid hormones increase SHBG production indirectly by increasing HNF-4α gene expression, and by reducing cellular palmitate levels that further contribute to increased HNF-4α levels in hepatocytes.
Satisficing: A 'Pretty Good' Heuristic
Authors: Bendor Jonathan Brodie , Kumar Sunil , Siegel David A
Published: April 2009

One of the best known ideas in the study of bounded rationality is Simon's satisficing; yet we still lack a standard formalization of the heuristic and its implications. We propose a mathematical model of satisficing which explicitly represents agents' aspirations and which explores both single-person and multi-player contexts. The model shows that satisficing has a signature performance-profile in both contexts: (1) it can induce optimal long-run behavior in one class of problems but not in the complementary class; and (2) in the latter, it generates behavior that is sensible but not optimal. The model also yields empirically testable predictions: in certain bandit-problems it pins down the limiting probabilities of each arm's use, and it provides an ordering of the arms' dynamical use-probabilities as well.
Reduced-Function SLC22A1 Polymorphisms Encoding Organic Cation Transporter 1 and Glycemic Response to Metformin: A GoDARTS Study
Authors: Zhou Kaixin , Donnelly Louise A. , Kimber Charlotte H. , Donnan Peter T. , Doney Alex S.F. , Leese Graham , Hattersley Andrew T. , McCarthy Mark I. , Morris Andrew D. , Palmer Colin N.A. , Pearson Ewan R.
Published: April 2009

OBJECTIVE

Metformin is actively transported into the liver by the organic cation transporter (OCT)1 (encoded by SLC22A1). In 12 normoglycemic individuals, reduced-function variants in SLC22A1 were shown to decrease the ability of metformin to reduce glucose excursion in response to oral glucose. We assessed the effect of two common loss-of-function polymorphisms in SLC22A1 on metformin response in a large cohort of patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

The Diabetes Audit and Research in Tayside Scotland (DARTS) database includes prescribing and biochemistry information and clinical phenotypes of all patients with diabetes within Tayside, Scotland, from 1992 onwards. R61C and 420del variants of SLC22A1 were genotyped in 3,450 patients with type 2 diabetes who were incident users of metformin. We assessed metformin response by modeling the maximum A1C reduction in 18 months after starting metformin and investigated whether a treatment target of A1C <7% was achieved. Sustained metformin effect on A1C between 6 and 42 months was also assessed, as was the time to metformin monotherapy failure. Covariates were SLC22A1 genotype, BMI, average drug dose, adherence, and creatinine clearance.

RESULTS

A total of 1,531 patients were identified with a definable metformin response. R61C and 420del variants did not affect the initial A1C reduction (P = 0.47 and P = 0.92, respectively), the chance of achieving a treatment target (P = 0.83 and P = 0.36), the average A1C on monotherapy up to 42 months (P = 0.44 and P = 0.75), or the hazard of monotherapy failure (P = 0.85 and P = 0.56).

CONCLUSIONS

The SLC22A1 loss-of-function variants, R61C and 420del, do not attenuate the A1C reduction achieved by metformin in patients with type 2 diabetes.
PTPN2, a Candidate Gene for Type 1 Diabetes, Modulates Interferon-γ–Induced Pancreatic β-Cell Apoptosis
Authors: Moore Fabrice , Colli Maikel L. , Cnop Miriam , Esteve Mariana Igoillo , Cardozo Alessandra K. , Cunha Daniel A. , Bugliani Marco , Marchetti Piero , Eizirik Décio L.
Published: April 2009

OBJECTIVE

The pathogenesis of type 1 diabetes has a strong genetic component. Genome-wide association scans recently identified novel susceptibility genes including the phosphatases PTPN22 and PTPN2. We hypothesized that PTPN2 plays a direct role in β-cell demise and assessed PTPN2 expression in human islets and rat primary and clonal β-cells, besides evaluating its role in cytokine-induced signaling and β-cell apoptosis.

RESEARCH DESIGN AND METHODS

PTPN2 mRNA and protein expression was evaluated by real-time PCR and Western blot. Small interfering (si)RNAs were used to inhibit the expression of PTPN2 and downstream STAT1 in β-cells, allowing the assessment of cell death after cytokine treatment.

RESULTS

PTPN2 mRNA and protein are expressed in human islets and rat β-cells and upregulated by cytokines. Transfection with PTPN2 siRNAs inhibited basal- and cytokine-induced PTPN2 expression in rat β-cells and dispersed human islets cells. Decreased PTPN2 expression exacerbated interleukin (IL)-1β + interferon (IFN)-γ–induced β-cell apoptosis and turned IFN-γ alone into a proapoptotic signal. Inhibition of PTPN2 amplified IFN-γ–induced STAT1 phosphorylation, whereas double knockdown of both PTPN2 and STAT1 protected β-cells against cytokine-induced apoptosis, suggesting that STAT1 hyperactivation is responsible for the aggravation of cytokine-induced β-cell death in PTPN2-deficient cells.

CONCLUSIONS

We identified a functional role for the type 1 diabetes candidate gene PTPN2 in modulating IFN-γ signal transduction at the β-cell level. PTPN2 regulates cytokine-induced apoptosis and may thereby contribute to the pathogenesis of type 1 diabetes.
Efficacy of oral rehydration therapy solutions containing sodium bicarbonate or sodium acetate for treatment of calves with naturally acquired diarrhea, moderate dehydration, and strong ion acidosis
Authors: Sen Ismail , Altunok Vahdettin , Ok Mahmut , Coskun Alparslan , Constable Peter D.
Published: April 2009

Objective—To determine and compare the effects of 4 oral replacement therapy (ORT) solutions on acid-base balance, abomasal emptying rate, and plasma volume expansion in calves with naturally acquired diarrhea and moderate dehydration.

Design—Prospective study.

Animals—20 calves.

Procedures—20 calves up to 45 days of age were randomly allocated (n = 5/group) to receive 2 L of 1 of 4 treatments via oroesophageal intubation: sodium bicarbonate (150 mmol/L or 300 mmol/L) or sodium acetate (150 mmol/L or 300 mmol/L). The 4 test solutions contained acetaminophen (50 mg/kg [22.7 mg/lb]) and 50 g of glucose monohydrate. Jugular venous blood samples were obtained periodically before and after administration of the ORT solution. Abomasal emptying rate was determined by use of the time to maximal plasma acetaminophen concentration.

Results—Plasma bicarbonate concentration increased more rapidly in calves administered bicarbonate-containing ORT solutions, whereas the rate of systemic alkalinization, as assessed via blood pH, did not differ consistently among treatments. The 300 mmol/L ORT solutions were emptied at a significantly slower rate from the abomasum than 150 mmol/L ORT solutions, with no difference in emptying rate between acetate and bicarbonate-con-taining ORT solutions of similar molality. The 300 mmol/L sodium acetate ORT solution significantly increased plasma volume.

Conclusions and Clinical Relevance—Clinically important differences in the resuscitative response to 300 mmol/L or 150 mmol/L ORT solutions of sodium acetate or sodium bicarbonate were not identified.
Prevalence of and risk factors for serum antibodies against Leptospira serovars in US veterinarians
Authors: Whitney Ellen A. Spotts , Ailes Elizabeth , Myers Lee M. , Saliki Jeremiah T. , Berkelman Ruth L.
Published: April 2009

Objective—To determine the seroprevalence of antibodies against Leptospira serovars among veterinarians and identify risk factors for seropositivity in veterinary care settings.

Design—Seroepidemiologic survey.

Study Population—Veterinarians attending the 2006 AVMA Annual Convention.

Procedures—Blood samples were collected from 511 veterinarians, and serum was harvested for a microcapsule agglutination test (MAT) to detect antibodies against 6 serovars of Leptospira. Aggregate data analysis was performed to determine the ratio of the odds of a given exposure (eg, types of animals treated or biosafety practices) in seropositive individuals to the odds in seronegative individuals.

Results—Evidence of previous leptospiral infection was detected in 2.5% of veterinarians. Most veterinarians reported multiple potential exposures to Leptospira spp and other pathogens in the previous 12 months, including unintentional needlestick injuries (379/511 [74.2%]), animal bites (345/511 [67.5%]), and animal scratches (451/511 [88.3%]). Treatment of a dog with an influenza-like illness within the past year was associated with seropositivity for antibodies against Leptospira spp.

Conclusions and Clinical Relevance—Veterinarians are at risk for leptospirosis and should take measures to decrease potential exposure to infectious agents in general. Diagnostic tests for leptospirosis should be considered when veterinarians have febrile illnesses of unknown origin.
THE CONCEPTUAL MODEL OF CONSTRUCTION AND REAL ESTATE NEGOTIATION
Authors: Urbanavičienė Vita , Kaklauskas Artūras , Zavadskas Edmundas K.
Published: April 2009

Negotiations are common in many activities; the sectors of construction and real estate are not an exception: here the negotiations are an inseparable part of the real estate buying and selling process. The article analyses scientific research related to negotiations and presents the developed model for multiple criteria analysis of construction and real estate negotiations. The analysis of the negotiation processes in construction and real estate and the analysis of the relevant support for decision‐making in negotiations must be thorough; it must consider not only economic but also political, legal, socio‐cultural, psychological, consumer behaviour, technological, quality of life and other issues. The developed model enables to analyse the combination of the real estate negotiation process, the improvement of its efficiency through use of decision support and voice stress analysis technology and the participating stakeholder groups seeking their goals together with the influencing external macro and micro environment. The paper dwells on the components of this model. Santruka Derybos nuolatos vyksta daugelyje veiklos sričiu, neaplenkdamos ir statybos bei NT sektoriu, kur jos yra neatsiejama nekilnojamojo turto pirkimo ir pardavimo proceso dalis. Straipsnyje analizuojami mokslininku tyrimai derybu srityje ir pristatomas sukurtas statybos ir NT derybu daugiakriterines analizes modelis. Nagrinejant statybos ir NT derybu procesa bei taikoma parama derybu sprendimams priimti, būtina tai nagrineti išsamiai, kreipiant demesi ne tik i ekonominius, bet ir i politinius, teisinius, socialinius, kultūrinius, psichologinius, vartotoju elgsenos, technologinius, gyvenimo kokybes ir pan. klausimus. Sukurtas modelis leidžia analizuoti NT derybu procesa, jo efektyvumo didinima, taikant sprendimu paramos ir balso analizes technologijas, joje dalyvaujančias ir savo tikslus norinčias igyvendinti suinteresuotas grupes bei jas veikiančia išorine makro‐ ir mikroaplinka kaip visuma. Straipsnyje aptartos sukurta modeli sudarančios sudetines dalys.
SUSTAINABILITY ASSESSMENT FOR CORPORATE MANAGEMENT OF ENERGY PRODUCTION AND SUPPLY COMPANIES FOR LITHUANIA
Authors: Stasiškienė Žaneta , Šliogerienė Jūratė
Published: April 2009

Corporate responsibility has become an important issue for management to address. The responsibility of the organization for the public environment (ecological, social and economic aspects of the environment) has become a matter of management attention referring to the entire organization and all major stakeholders. Therefore safe, environmentally sound, and economically viable energy production and supply should be essential part of management issues. The anticipated closure of the Ignalina Nuclear Power Plant at 2009 will change the situation of electricity generation in Lithuania significantly. The costs of electricity generation and distribution are the most important criteria shaping decisions in the energy production and supply companies. Sound energy and environmental accounting must be the basis of any strategic decision making in order to keep up with the increasing complexity of energy and environmental problems. Efficiency, equity, ecological integrity, and technological change are introduced as fundamental aspects that need to be considered in a comprehensive sustainable energy production and supply framework. Since these issues cannot be suitably included within the frame of a single model, a combination of ecological, economic, technological and social measures for different aspects of Lithuanian energy system and sustainable development are analysed.

Santruka

Imoniu atsakomybe už aplinka (socialiniu, ekologiniu, ekonominiu aspektu) yra vienas svarbiausiu klausimu nustatant imoniu veiklos prioritetus ir priimant veiklos sprendimus. Svarbiausias šiandienos energetikos uždavinys ‐ patikima saugios, ekologiškai švarios, efektyvios ir ekonomiškai patrauklios energijos gavyba. Ši tiksla igyvendinti imanoma tinkamai formuojant energetikos ūkio valdymo politika, keičiant ir nustatant valdymo, naudojimo išlaidas, ivertinant energetikos infrastruktūros poveiki ekologijai. Svarbiausias veiksnys, lemiantis pasirenkamus sprendimus elektros energijos gamybos ir paskirstymo sektoriuje, yra energijos gamybos ir paskirstymo kaina. Gamybos ir paskirstymo kainu lygiui itaka daro turto struktūra, i kaina integruoti aplinkos taršos bei išoriniu taršo sanaudu mokesčiai. Tačiau po 2009 m., uždarius Ignalinos atomine elektrine, situacija Lietuvos elektros energetikos sektoriuje pasikeis iš esmes, nes pasikeis energijos gamybos šaltiniai. Siekiant sudaryti aplinkai visapusiškai saugia elektros energijos gamybos ir perdavimo struktūra, efektyvumas, ekologinis integruotumas, technologinis inovatyvumas yra tie pagrindiniai kriterijai, kuriuos būtina vertinti rengiant sprendimus. Elektros energetikos sektoriuje veiksmingas gali būti tik toks valdymo modelis, kuris suderins ekologinius, socialinius, technologinius aspektus su darnios aplinkos analize.
Adverse Childhood Experiences and Sleep Disturbances Among Puerto Rican Young Adults
Authors: Olsen Eudora L. , April-Sanders Ayana K. , Bird Hector R. , Canino Glorisa J. , Duarte Cristiane S. , Suglia Shakira F.
Published: April 2024

Importance

Sleep quality is a known marker of overall health. Studies suggest that adverse childhood experiences (ACEs) are associated with sleep disturbances among children and adults.

Objective

To examine the association of retrospective and prospective ACEs with sleep quality among a cohort of Puerto Rican young adults from 2 sociocultural contexts.

Design, Setting, and Participants

This prospective cohort study used data from the Boricua Youth Study (BYS), a population-based study representing Puerto Rican children from the South Bronx, New York, and Puerto Rico conducted from August 2000 to August 2003. Participants who were 5 to 9 years of age at enrollment in the BYS and who participated in wave 4 of the BYS took part in the Health Assessment (HA) when they were 18 to 29 years of age, from April 2013 to August 2017. Of the eligible 982 participants, 813 (82.8%) participated in the HA. Statistical analysis was conducted from January 2023 to January 2024.

Exposures

Prospective ACEs measured from parent and youth responses and retrospective ACEs measured among young adults using questions from the validated ACE questionnaire from the original ACEs study conducted by Kaiser Permanente and the Centers for Disease Control and Prevention and published in 1998. Analysis included 8 overlapping items from both questionnaires.

Outcomes

Sleep quality was assessed in the HA with the Pittsburgh Sleep Quality Index. The summary score included 7 components of the Pittsburgh Sleep Quality Index. The hypothesis was formulated after data collection. Sleep quality information was gathered at the same time as retrospective ACEs in the HA.

Results

Of the 813 participants, 438 (53.9%) lived in Puerto Rico as children, 411 (50.6%) identified as female, and the mean (SE) age of participants was 22.9 (0.07) years. After adjusting for sociodemographic factors, retrospective ACEs had a significant association with worse sleep outcomes (β [SE] = 0.29 [0.07]; 95% CI, 0.15-0.44; P < .001). Prospective ACEs did not have a significant association with sleep quality, after adjusting for sociodemographic factors (β [SE] = 0.05 [0.10]; 95% CI, –0.14 to 0.24; P = .59).

Conclusions and Relevance

This study suggests that there is a significant association between retrospective ACEs and sleep quality among Puerto Rican young adults, after adjusting for sociodemographic factors. Prospective ACEs were not significantly associated with sleep disturbances, after adjusting for sociodemographic factors. Addressing ACEs reported in young adulthood may help reduce sleep disorders.
Opioid Overdose Knowledge Among Adolescents and Young Adults
Authors: Freibott Christina E. , Vest Noel , Stein Michael D. , Lipson Sarah Ketchen
Published: April 2024

This cross-sectional study examines awareness of opioid overdose, the ability to administer naloxone, and the willingness to help during an overdose on college campuses across the US.
A case of immunotherapy‐responsive autoimmune hemichorea
Authors: Rodin Rachel E. , Venna Nagagopal , Balaban Denis T.
Published: April 2024

Introduction

Subacute adult‐acquired hemichorea is a striking presentation with a broad differential, including ischemic, metabolic, and inflammatory causes.

Case

We encountered a 74‐year‐old woman with rapid onset of hemichorea and associated encephalopathy. Following a thorough workup without identification of clear imaging or laboratory abnormalities, we empirically treated with IVIg. Her hemichorea dramatically improved. Due to relapses of hemichorea, she required repeat immunotherapy with IVIg or high dose steroids followed by maintenance mycophenolate.

Discussion

This case of seronegative autoimmune hemichorea highlights the importance of a high index of suspicion for an inflammatory etiology of chorea when other causes are ruled out and performing an immunotherapy trial.
Tribocorrosion Characteristics of Hard Anodized Al Alloys on Hydrogen Valve Application for Fuel Cell Electric Vehicles
Authors: Shin Dong‐Ho , Kim Seong‐Jong
Published: April 2024

In this study, the electrochemical and mechanical characteristics of 6061‐T6 aluminum alloy and hard anodized specimens are investigated after tribocorrosion experiments with rotational speed in dry, distilled water, and sulfuric acid solution. The tribocorrosion experiments indicate that the corrosion potential of aluminum alloys and hard anodized specimens decrease with the initiation of friction/wear. In particular, the increase in the wear track width of an aluminum alloy and the exposure of the base material by completely destroying the anodized layers of the hard anodized specimens dramatically decrease the corrosion potential. Compared to the dry conditions, both the width and depth of damage in the distilled water and sulfuric acid solution increase dramatically. However, damage in the distilled water and sulfuric acid solutions do not present a significant difference. The results are attributed to the fact that the presence of fluid has a greater impact on damage degree in a material than corrosion. In particular, the brittleness and porosity of a hard anodized layer facilitates the impingement and penetration of fluid, making it relatively easy to generate and propagate cracks. These cracks accelerate the degradation and damage to the material by synergistic effects of wear and corrosion.
Temperature‐Induced Structural Evolution and Magnetism in Self‐Intercalated V1+xSe2 Nanoplates
Authors: Guzman Roger , Liu Hongtao , Bian Ce , Bao Lihong , Shen Cheng‐Min , Gao Hong‐Jun , Zhou Wu
Published: April 2024

2D van der Waals (vdW) magnets provide the ideal platform for studying magnetism at low dimensions, where the magnetic properties can be further tuned by intercalating magnetic species and manipulating their stoichiometry and local atomic configuration. However, achieving stoichiometric intercalated 2D magnets necessitates precise control of growth parameters to avoid local compositional variations, which fosters phase coexistence that significantly impacts magnetic properties. Here a comprehensive scanning transmission electron microscopy (STEM) examination of the structural evolution in chemical vapor deposition (CVD)‐grown self‐intercalated V1+xSe2 nanoplates is shown, exploring their response to annealing temperature variations and the subsequent influence on magnetic properties. By combining ex situ and in situ post‐growth annealing, the rearrangement of intercalants is directly observed at the interlayer and identify a structural phase transition of the nanodomains embedded in the VSe2 matrix from V3Se4 to a V5Se8 structure occurring at ≈250 °C. The interlayer reconstruction is manifested by a positive‐to‐negative cross‐over in the magnetoresistance and an upturn in resistivity at low temperatures. The results provide new ways for tailoring 2D vdW magnets through post‐growth thermal annealing.
Composite Electrolytes with Li2CO3‐Free Garnets Achieved by One‐Step Poly(propylene carbonate) Treatment for High‐Rate and Long‐Life Solid Lithium Batteries
Authors: Wang Nan , Jia Mengyang , Bi Zhijie , Guo Xiangxin
Published: April 2024

Garnet‐based composite electrolytes show great potential in building high‐energy‐density solid lithium batteries. However, naturally formed Li2CO3 on garnets owing to air exposure hinders the Li‐ion transport and triggers undesirable performance deterioration. Based on the reaction between basic Li2CO3 and poly(propylene carbonate) (PPC) with a product of propylene carbonate (PC), composite electrolytes with homogeneously distributed Li2CO3‐free garnets as well as PC are fabricated in one step without the post‐treatment of garnet powders in both polyethylene oxide (PEO) and polyvinylidene fluoride (PVDF)‐based electrolytes. The formed PC component further decreases the crystallization of PEO and reduces the grain size of PVDF, leading to improved ion transport in PEO and the suppression of PVDF dehydrofluorination. Consequently, the PPC‐treated garnets enable high ionic conductivities of 3.40 × 10−4 and 1.75 × 10−4 S cm−1 at 30 °C, respectively, in PEO:garnet and PVDF:garnet electrolytes, as well as great electrochemical stability against Li‐metal with a lifespan over 1000 h in Li symmetrical cells at 0.1 mA cm−2. Superior stable cycles are thus realized in both LiFePO4|PEO:garnet|Li and LiNi0.6Co0.2Mn0.2O2|PVDF:garnet|Li cells. These above results demonstrate that the one‐step treatment used here helps the enhancement of Li‐ion transport in composite electrolytes, thus essential for building high‐rate and long‐life solid lithium batteries (SLBs).
A Multifunctional Hydrogel with Photothermal Antibacterial and AntiOxidant Activity for Smart Monitoring and Promotion of Diabetic Wound Healing
Authors: Wang Yue , Liu Kun , Wei Wenying , Dai Honglian
Published: April 2024

Persistent oxidative stress and bacterial infection are significant challenges that impede diabetic wound healing. By combining diagnosis and treatment, pH variation on the wound tissue can be monitored in real time, and precise treatment can be carried out promptly to promote diabetic wound healing. In this study, a lipoic acid‐modified chitosa (LAMC) hydrogel is constructed via an amidation reaction, and ceria oxide‐molybdenum disulfide nanoparticles with a polydopamine layer (C@M@P), along with carbon quantum dots (CDs) synthesized by a hydrothermal method, are loaded into the hydrogel, thus developing a diagnostic and therapeutic hydrogel (LAMC/CD‐C@M@P). By incorporating CDs, the hydrogel exhibits high sensitivity and reversibility to pH under ultraviolet light. Furthermore, the images of hydrogels can be collected using smartphones and converted into wound pH signals, providing a means for early detection of bacterial infection. Notably, the LAMC/CD‐C@M@P hydrogel exhibits excellent photothermal antibacterial capability against Staphylococcus aureus and Escherichia coli and remarkable antioxidant and anti‐inflammatory abilities to alleviate reactive oxygen species and relieve inflammation response. In summary, this multifunctional hydrogel offers great potential as an innovative wound dressing platform, representing a significant advancement in chronic wound management.