bluuebunny/crossref_metadata_2025 huggingface dataset:
ASIC3 Channels Integrate Agmatine and Multiple Inflammatory Signals through the Nonproton Ligand Sensing Domain
Authors: Li Wei-Guang , Yu Ye , Zhang Zhu-Dan , Cao Hui , Xu Tian-Le
Published: January 2011

Background:

Acid-sensing ion channels (ASICs) have long been known to sense extracellular protons and contribute to sensory perception. Peripheral ASIC3 channels represent natural sensors of acidic and inflammatory pain. We recently reported the use of a synthetic compound, 2-guanidine-4-methylquinazoline (GMQ), to identify a novel nonproton sensing domain in the ASIC3 channel, and proposed that, based on its structural similarity with GMQ, the arginine metabolite agmatine (AGM) may be an endogenous nonproton ligand for ASIC3 channels.

Results:

Here, we present further evidence for the physiological correlation between AGM and ASIC3. Among arginine metabolites, only AGM and its analog arcaine (ARC) activated ASIC3 channels at neutral pH in a sustained manner similar to GMQ. In addition to the homomeric ASIC3 channels, AGM also activated heteromeric ASIC3 plus ASIC1b channels, extending its potential physiological relevance. Importantly, the process of activation by AGM was highly sensitive to mild acidosis, hyperosmolarity, arachidonic acid (AA), lactic acid and reduced extracellular Ca2+. AGM-induced ASIC3 channel activation was not through the chelation of extracellular Ca2+as occurs with increased lactate, but rather through a direct interaction with the newly identified nonproton ligand sensing domain. Finally, AGM cooperated with the multiple inflammatory signals to cause pain-related behaviors in an ASIC3-dependent manner.

Conclusions:

Nonproton ligand sensing domain might represent a novel mechanism for activation or sensitization of ASIC3 channels underlying inflammatory pain-sensing under in vivo conditions.
Sex-related differences in motor learning and performance
Authors: Moreno-Briseño Pablo , Díaz Rosalinda , Campos-Romo Aurelio , Fernandez-Ruiz Juan
Published: January 2011

Gender differences have been shown across many domains, and motor skills are no exception. One of the most robust findings is a significant sex difference in throwing accuracy, which reflects the advantage of men in targeting abilities. However, little is known about the basis of this difference. To try to dissect possible mechanisms involved in this difference, here we tested for gender variations in a prism adaptation throwing task. We tested 154 subjects in a visuomotor prism adaptation task that discriminates between motor performance, visuomotor adaptation and negative aftereffects. Our results corroborate men's significant better throwing accuracy, although there were no adaptation differences between genders. In contrast, women showed significant larger negative aftereffects, which could be explained by a larger contribution of spatial alignment. These results suggest that different learning mechanisms, like strategic calibration and spatial alignment, may have different contributions in men and women.
Impact of Alu repeats on the evolution of human p53 binding sites
Authors: Cui Feng , Sirotin Michael V , Zhurkin Victor B
Published: January 2011

Background

The p53 tumor suppressor protein is involved in a complicated regulatory network, mediating expression of ~1000 human genes. Recent studies have shown that many p53 in vivo binding sites (BSs) reside in transposable repeats. The relationship between these BSs and functional p53 response elements (REs) remains unknown, however. We sought to understand whether the p53 REs also reside in transposable elements and particularly in the most-abundant Alu repeats.

Results

We have analyzed ~160 functional p53 REs identified so far and found that 24 of them occur in repeats. More than half of these repeat-associated REs reside in Alu elements. In addition, using a position weight matrix approach, we found ~400,000 potential p53 BSs in Alu elements genome-wide. Importantly, these putative BSs are located in the same regions of Alu repeats as the functional p53 REs - namely, in the vicinity of Boxes A/A' and B of the internal RNA polymerase III promoter. Earlier nucleosome-mapping experiments showed that the Boxes A/A' and B have a different chromatin environment, which is critical for the binding of p53 to DNA. Here, we compare the Alu-residing p53 sites with the corresponding Alu consensus sequences and conclude that the p53 sites likely evolved through two different mechanisms - the sites overlapping with the Boxes A/A' were generated by CG → TG mutations; the other sites apparently pre-existed in the progenitors of several Alu subfamilies, such as AluJo and AluSq. The binding affinity of p53 to the Alu-residing sites generally correlates with the age of Alu subfamilies, so that the strongest sites are embedded in the 'relatively young' Alu repeats.

Conclusions

The primate-specific Alu repeats play an important role in shaping the p53 regulatory network in the context of chromatin. One of the selective factors responsible for the frequent occurrence of Alu repeats in introns may be related to the p53-mediated regulation of Alu transcription, which, in turn, influences expression of the host genes.

Reviewers

This paper was reviewed by Igor B. Rogozin (nominated by Pavel A. Pevzner), Sandor Pongor, and I. King Jordan.
Edible Lepidoptera in Mexico: Geographic distribution, ethnicity, economic and nutritional importance for rural people
Authors: Ramos-Elorduy Julieta , Moreno José MP , Vázquez Adolfo I , Landero Ivonne , Oliva-Rivera Héctor , Camacho Víctor HM
Published: January 2011

In this paper, we reported the butterflies and moths that are consumed in Mexico. We identified 67 species of Lepidoptera that are eaten principally in their larval stage in 17 states of Mexico. These species belong to 16 families: Arctiidae, Bombycidae, Castniidae, Cossidae, Geometridae, Hepialidae, Hesperiidae, Lasiocampidae, Noctuidae, Nymphalidae, Papilionidae, Pieridae, Pyralidae, Saturniidae, Sesiidae, and Sphingidae.

Saturniidae, Pieridae, Noctuidae and Nymphalidae were the more species consumed with 16, 11, 9, and 8 species, respectively.

The genera with the largest numbers of species were:Phassus,Phoebis,HylesiaandSpodoptera, with three species.

Their local distribution, corresponding to each state of Mexico, is also presented.
Oxygen supplementation facilitating successful prosthetic fitting and rehabilitation of a patient with severe chronic obstructive pulmonary disease following trans-tibial amputation: a case report
Authors: Sohal Jasdeep , Arneja Amarjit , Sharma Sat
Published: January 2011

Introduction

Dysvascular amputations are increasingly performed in patients with underlying cardiac and pulmonary disorders. A limb prosthesis is rarely offered to patients with severe chronic obstructive pulmonary disease because of their inability to achieve the high energy expenditure required for prosthetic ambulation. We describe a case of successful prosthetic fitting and rehabilitation of a patient with severe chronic obstructive pulmonary disease with the aid of oxygen supplementation.

Case presentation

A 67-year-old aboriginal woman with severe chronic obstructive pulmonary disease and hypercapnic respiratory failure underwent right trans-tibial (below the knee) amputation for severe foot gangrene. An aggressive rehabilitation program of conditioning exercises and gait training utilizing oxygen therapy was initiated. She was custom-fitted with a right trans-tibial prosthesis. A rehabilitation program improved her strength, endurance and stump contracture, and she was able to walk for short distances with the prosthesis. The motion analysis studies showed a cadence of 73.5 steps per minute, a velocity of 0.29 meters per second and no difference in right and left step time and step length.

Conclusion

This case report illustrates that patients with significant severe chronic obstructive pulmonary disease can be successfully fitted with limb prostheses and undergo rehabilitation using supplemental oxygen along with optimization of their underlying comorbidities. Despite the paucity of published information in this area, prosthesis fitting and rehabilitation should be considered in patients who have undergone amputation and have severe chronic obstructive disease.
Spontaneous biloma managed with endoscopic retrograde cholangiopancreatography and percutaneous drainage: a case report
Authors: Bas Gurhan , Okan Ismail , Sahin Mustafa , Eryılmaz Ramazan , Isık Arda
Published: January 2011

Introduction

Spontaneous biloma formation is a very rare condition, which mandates immediate treatment.

Case presentation

An 80-year-old Caucasian man was referred to our department with a diagnosis of intra-abdominal collection located in his right upper quadrant. Further radiological examination demonstrated multiple calculi in his gallbladder and common bile duct. Our patient underwent endoscopic retrograde cholangiopancreatography and the stones in the common bile duct were extracted. Percutaneous drainage of the abdominal collection revealed a spontaneous biloma formation. Continuous drainage of bile persisted for one week, so endoscopic retrograde cholangiopancreatography was repeated and a 10Fr stent was placed; subsequently the biliary leak ceased and our patient was discharged. A control abdominal computed tomography did not show any residual fluid collection.

Conclusion

Spontaneous biloma formation is a very rare incidence; awareness is necessary for prompt recognition and treatment.
Expression and prognostic significance of cancer-testis antigens (CTA) in intrahepatic cholagiocarcinoma
Authors: Zhou Jin-xue , Li Yin , Chen Sun-xiao , Deng An-mei
Published: January 2011

Background

Cancer-testis antigens (CTAs) are suitable targets for cancer-specific immunotherapy. The aim of the study is to investigate the expression of CTAs in intrahepatic cholagiocarcinoma (IHCC) and evaluate their potential therapeutic values.

Methods

Eighty-nine IHCC patients were retrospectively assessed for their expression of CTAs and HLA Class I by immunohistochemistry using the following antibodies: MA454 recognizing MAGE-A1, 57B recognizing multiple MAGE-A (MAGE-A3/A4), E978 recognizing NY-ESO-1, and EMR8-5 recognizing HLA class I. The clinicopathological and prognostic significance of individual CTA markers and their combination were further evaluated.

Results

The expression rates of MAGE-A1, MAGE-A3/4 and NY-ESO-1 were 29.2%, 27.0% and 22.5%, respectively. The concomitant expression of CTAs and HLA class I antigen was observed in 33.7% of the IHCC tumors. We found that positive MAGE-3/4 expression correlated with larger tumor size (≥ 5 cm), tumor recurrence and poor prognosis. Moreover, we identified 52 cases (58.4%) of IHCC patients with at least one CTA marker expression, and this subgroup displayed a higher frequency of larger tumor size and a shorter survival than the other cases. Furthermore, expression of at least one CTA marker was also an independent prognostic factor in patients with IHCC.

Conclusion

Our data suggest that specific immunotherapy targeted CTAs might be a novel treatment option for IHCC patients.
Small airway remodeling in acute respiratory distress syndrome: a study in autopsy lung tissue
Authors: Morales Maina MB , Pires-Neto Ruy C , Inforsato Nicole , Lanças Tatiana , da Silva Luiz FF , Saldiva Paulo HN , Mauad Thais , Carvalho Carlos RR , Amato Marcelo BP , Dolhnikoff Marisa
Published: January 2011

Introduction

Airway dysfunction in patients with the Acute Respiratory Distress Syndrome (ARDS) is evidenced by expiratory flow limitation and dynamic hyperinflation. These functional alterations have been attributed to closure/obstruction of small airways. Airway morphological changes have been reported in experimental models of acute lung injury, characterized by epithelial necrosis and denudation in distal airways. To date, however, no study has focused on the morphological airway changes in lungs from human subjects with ARDS. The aim of this study is to evaluate structural and inflammatory changes in distal airways in ARDS patients.

Methods

We retrospectively studied autopsy lung tissue from subjects who died with ARDS and from control subjects who died of non pulmonary causes. Using image analysis, we quantified the extension of epithelial changes (normal, abnormal and denudated epithelium expressed as percentages of the total epithelium length), bronchiolar inflammation, airway wall thickness, and extracellular matrix (ECM) protein content in distal airways. The Student's t-test or the Mann-Whitney test was used to compare data between the ARDS and control groups. Bonferroni adjustments were used for multiple tests. The association between morphological and clinical data was analyzed by Pearson rank test.

Results

Thirty-one ARDS patients (A: PaO2/FiO2 ≤200, 45 ± 14 years, 16 males) and 11 controls (C: 52 ± 16 years, 7 males) were included in the study. ARDS airways showed a shorter extension of normal epithelium (A:32.9 ± 27.2%, C:76.7 ± 32.7%, P < 0.001), a larger extension of epithelium denudation (A:52.6 ± 35.2%, C:21.8 ± 32.1%, P < 0.01), increased airway inflammation (A:1(3), C:0(1), P = 0.03), higher airway wall thickness (A:138.7 ± 54.3 μm, C:86.4 ± 33.3 μm, P < 0.01), and higher airway content of collagen I, fibronectin, versican and matrix metalloproteinase-9 (MMP-9) compared to controls (P ≤0.03). The extension of normal epithelium showed a positive correlation with PaO2/FiO2 (r2 = 0.34; P = 0.02) and a negative correlation with plateau pressure (r2 = 0.27; P = 0.04). The extension of denuded epithelium showed a negative correlation with PaO2/FiO2 (r2 = 0.27; P = 0.04).

Conclusions

Structural changes in small airways of patients with ARDS were characterized by epithelial denudation, inflammation and airway wall thickening with ECM remodeling. These changes are likely to contribute to functional airway changes in patients with ARDS.
Clinical features of invasive bronchial-pulmonary aspergillosis in critically ill patients with chronic obstructive respiratory diseases: a prospective study
Authors: He Hangyong , Ding Lin , Li Fang , Zhan Qingyuan
Published: January 2011

Introduction

Critically ill patients with chronic obstructive respiratory diseases (CORD) who require intensive care unit (ICU) admission are at particular risk for invasive bronchial-pulmonary aspergillosis (IBPA). The purpose of this study is to investigate clinical features for rapid recognition of IBPA in critically ill patients with CORD.

Methods

We included 55 consecutive CORD patients in a respiratory ICU in a prospective, single-center, cohort study. In this study, IBPA combined two entities: ATB and IPA.

Results

Thirteen of 55 patients were diagnosed with IBPA. Before ICU admission, three variables were independent predictors of IBPA with statistical significance: more than three kinds of antibiotics used before the ICU admission, accumulated doses of corticosteroids (>350 mg) received before the ICU admission, and APACHE II scores >18 (OR, 1.208; P = 0.022; OR, 8.661; P = 0.038; and OR, 19.488; P = 0.008, respectively). After ICU admission, more IBPA patients had a high fever (>38.5°C) (46.2% versus 11.9%; P = 0.021), wheeze without exertion (84.6% versus 50.0%; P = 0.027), dry rales (84.6% versus 40.4%; P = 0.005), higher white blood cell counts (21 × 109/L versus 9.4 × 109/L; P = 0.012), lower mean arterial pressures (77.9 mm Hg versus 90.5 mm Hg; P = 0.019), and serum creatinine clearances (36.2 ml/min versus 68.8 ml/min; P < 0.001), and liver-function and coagulation abnormalities. Bronchospasm, sputum ropiness, and plaque formation were more common for IBPA patients during bronchoscopy (66.7% versus 14.3%; P = 0.082; 18% versus 0; P = 0.169; and 73% versus 13%; P = 0.003, respectively). More IBPA patients had nodules and patchiness on chest radiograph on day 1 of admission, which rapidly progressed to consolidation on day 7. IBPA mortality was higher than that of non-IBPA patients (69.2% versus 16.7%; P = 0.001).

Conclusions

IBPA may be suspected in critically ill CORD patients with respiratory failure and clinical and bronchoscopic manifestations of severe infection, bronchospasm, and rapid progression of radiologic lesions that are irresponsive to steroids and antibiotics. To avoid misdiagnosis and establish the microbiologic etiology, early bronchoscopy and tight radiologic follow-up should be performed.
Audiomagnetotelluric characterization of range-front faults, Snake Range, Nevada
Authors: Asch Theodore H. , Sweetkind Donald S.
Published: January 2011

Two controlled-source audio-magnetotelluric (CSAMT) profiles were collected on the eastern flank of the Snake Range in eastern Nevada across geologically complex terrain to investigate the suspected presence of faults along the range front. The location of the range-bounding faults is not easily determined on geologic grounds because of the presence of extensive young sedimentary cover and overall geologic complexity. Characterization of the presence, location, and structural style of the range-front faults is critical to assessment of connectivity of groundwater aquifers near the mountain front and in adjacent alluvial basins. A total of 48 CSAMT soundings were recorded along two lines that were chosen to maximize subsurface geologic information. Two generations of faults were interpreted based on the CSAMT data: an older, low-angle fault that is cut by a younger, more steeply dipping fault. Lack of deep boreholes in the region required that the subsurface interpretation rely on analogy from surface outcrops within and adjacent to the study area. The success of the CSAMT method as applied in this study hinged on near-ideal collection conditions, the relatively high contrast in electrical resistivity provided by the rock types involved, and well-developed geologic conceptual models of the region.
Reverse Feeding Suppresses the Activity of the GH Axis in Rats and Induces a Preobesogenic State
Authors: Glad Camilla A.-M. , Kitchen Edward E. J. , Russ Gemma C. , Harris Sophie M. , Davies Jeffrey S. , Gevers Evelien F. , Gabrielsson Britt G. , Wells Timothy
Published: January 2011

Reversed feeding (RF) is known to disrupt hormone rhythmicity and metabolism. Although these effects may be mediated in part by phase inversion of glucocorticoid secretion, the precise mechanism is incompletely characterized. In this study, we demonstrate that acute nocturnal food deprivation in male rats suppressed the amplitude of spontaneous GH secretion during the dark phase by 62% (P < 0.001), without affecting baseline secretion. Prolonged RF, which reduced pituitary weight (by 22%; P < 0.05), also suppressed GH pulse height sufficiently to reduce skeletal growth (by 4–5%; P < 0.01) and terminal liver weight (by 11%; P < 0.001). Despite this suppression of the GH axis, proportionate adiposity was not elevated, probably due to the accompanying 16% reduction in cumulative food intake (P < 0.01). We demonstrate that RF also resulted in phase inversion of core clock gene expression in liver, abdominal white adipose tissue (WAT) and skeletal muscle, without affecting their expression patterns in the suprachiasmatic nucleus. In addition, RF resulted in phase inversion of hepatic peroxisome proliferator-activated receptor γ2 mRNA expression, a 3- to 5-fold elevation in fatty acid synthase mRNA in WAT in both light- and dark-phase samples (P < 0.01) and an elevation in muscle uncoupling protein 3 mRNA expression at the beginning of the light phase (P < 0.01). Consumption of a high-fat diet increased inguinal (by 36%; P < 0.05) and retroperitoneal WAT weight (by 72%; P < 0.01) only in RF-maintained rats, doubling the efficiency of lipid accumulation (P < 0.05). Thus, RF not only desynchronizes central and peripheral circadian clocks, and suppresses nocturnal GH secretion, but induces a preobesogenic state.
KT5823 Differentially Modulates Sodium Iodide Symporter Expression, Activity, and Glycosylation between Thyroid and Breast Cancer Cells
Authors: Beyer Sasha , Lakshmanan Aparna , Liu Yu-Yu , Zhang Xiaoli , Wapnir Irene , Smolenski Albert , Jhiang Sissy
Published: January 2011

Na+/I− symporter (NIS)-mediated iodide uptake into thyroid follicular cells serves as the basis of radioiodine therapy for thyroid cancer. NIS protein is also expressed in the majority of breast tumors, raising potential for radionuclide therapy of breast cancer. KT5823, a staurosporine-related protein kinase inhibitor, has been shown to increase thyroid-stimulating hormone-induced NIS expression, and thus iodide uptake, in thyroid cells. In this study, we found that KT5823 does not increase but decreases iodide uptake within 0.5 h of treatment in trans-retinoic acid and hydrocortisone-treated MCF-7 breast cancer cells. Moreover, KT5823 accumulates hypoglycosylated NIS, and this effect is much more evident in breast cancer cells than thyroid cells. The hypoglycosylated NIS is core glycosylated, has not been processed through the Golgi apparatus, but is capable of trafficking to the cell surface. KT5823 impedes complex NIS glycosylation at a regulatory point similar to brefeldin A along the N-linked glycosylation pathway, rather than targeting a specific N-glycosylated site of NIS. KT5823-mediated effects on NIS activity and glycosylation are also observed in other breast cancer cells as well as human embryonic kidney cells expressing exogenous NIS. Taken together, KT5823 will serve as a valuable pharmacological reagent to uncover mechanisms underlying differential NIS regulation between thyroid and breast cancer cells at multiple levels.
Stimulation of Lipogenesis as Well as Fatty Acid Oxidation Protects against Palmitate-Induced INS-1 β-Cell Death
Authors: Choi Sung-E. , Jung Ik-Rak , Lee Youn-Jung , Lee Soo-Jin , Lee Ji-Hyun , Kim Youngsoo , Jun Hee-Sook , Lee Kwan-Woo , Park Chan Bae , Kang Yup
Published: January 2011

Saturated fatty acids are generally cytotoxic to β-cells. Accumulation of lipid intermediates and subsequent activation of lipid-mediated signals has been suggested to play a role in fatty acid-induced toxicity. To determine the effects of lipid metabolism in fatty acid-induced toxicity, lipid metabolism was modulated by up- and down-regulation of a lipogenic or fatty acid oxidation pathway, and the effects of various modulators on palmitate (PA)-induced INS-1 β-cell death were then evaluated. Treatment with the liver X receptor agonist T0901317 reduced PA-induced INS-1 cell death, regardless of its enhanced lipogenic activity. Furthermore, transient expression of a lipogenic transcription factor sterol regulatory element binding protein-1c (SREBP-1c) was also protective against PA-induced cytotoxicity. In contrast, knockdown of SREBP-1c or glycerol-3-phosphate acyltransferase 1 significantly augmented PA-induced cell death and reduced T0901317-induced protective effects. Conversely, T0901317 increased carnitine PA transferease-1 (CPT-1) expression and augmented PA oxidation. CPT-1 inhibitor etomoxir or CPT-1 knockdown augmented PA-induced cell death and reduced T0901317-induced protective effects, whereas the peroxisome proliferator-activated receptor (PPAR)-α agonist bezafibrate reduced PA-induced toxicity. In particular, T0901317 reduced the levels of PA-induced endoplasmic reticulum (ER) stress markers, including phospho-eukaryotic initiation factor-2α, phospho-C-Jun N terminal kinase, and CCAAT/enhancer-binding protein homologous protein. In contrast, knockdown of SREBP-1c or glycerol-3-phosphate acyltransferase 1 augmented PA-induced ER stress responses. Results of these experiments suggested that stimulation of lipid metabolism, including lipogenesis and fatty acid oxidation, protected β-cells from PA-induced lipotoxicity and that protection through enhanced lipogenesis was likely due to reduced ER stress.
Human Endometrial Cells Express Elevated Levels of Pluripotent Factors and Are More Amenable to Reprogramming into Induced Pluripotent Stem Cells
Authors: Park Joo Hyun , Daheron Laurence , Kantarci Sibel , Lee Byung Seok , Teixeira Jose M.
Published: January 2011

The human endometrium is a tissue with remarkable plasticity and regenerative capacity. Additionally, endometrial cells can be retrieved using minimally invasive procedures, which makes them an ideal source for reprogramming into a pluripotent state. Endometrial cells were obtained from donors in their fifth decade and reprogrammed into induced pluripotent stem (iPS) cells using retroviral transduction with SOX2, OCT4, KLF4, and MYC. The human endometrial cells displayed accelerated expression of endogenous NANOG and OCT4 during reprogramming compared with neonatal skin fibroblasts. As a result, iPS cell colonies that could be subcultured and propagated were established as early as 12 d after transduction rather than the usually reported 3–4 wk for other cell types. After 3 wk of reprogramming, the human endometrial cells also yielded significantly higher numbers of iPS colonies in comparison with the neonatal skin fibroblasts. Although the efficiency of iPS colony formation varied depending on the donor, the basal level of endogenous expression of the defined factors was positively correlated with reprogramming efficiency. The reprogramming resulted in an average colony-forming efficiency of 0.49 ± 0.10%, with a range from 0.31–0.66%, compared with the neonatal skin fibroblasts, resulting in an average efficiency of 0.03 ± 0.00% per transduction, with a range from 0.02–0.03%. Our studies show that the human endometrium expresses elevated levels of pluripotent factors, which with additional defined factors, results in significantly more efficient and accelerated generation of induced pluripotent stem cells compared with conventional somatic cells.
The Molecular Mechanisms of Cervical Ripening Differ between Term and Preterm Birth
Authors: Holt Roxane , Timmons Brenda C. , Akgul Yucel , Akins Meredith L. , Mahendroo Mala
Published: January 2011

In the current study, the mechanisms of premature cervical ripening in murine models of preterm birth resulting from infection or early progesterone withdrawal were compared with the process of term cervical ripening. Tissue morphology, weight, gene expression, and collagen content along with immune cell populations were evaluated. Premature ripening induced by the progesterone receptor antagonist mifepristone results from an acceleration of processes in place during term ripening as well as partial activation of proinflammatory and immunosuppressive processes observed during postpartum repair. In contrast to term or mifepristone-induced preterm ripening, premature ripening induced in an infection model occurs by a distinct mechanism which is dominated by an influx of neutrophils into the cervix, a robust proinflammatory response and increased expression of prostaglandin-cyclooxygenase-endoperoxide synthase 2, important in prostaglandin biosynthesis. Key findings from this study confirm that cervical ripening can be initiated by more than one mechanism and is not necessarily an acceleration of the physiologic process at term. These results will influence current strategies for identifying specific etiologies of preterm birth and developing subsequent therapies.
Kisspeptin Regulates Gonadotroph and Somatotroph Function in Nonhuman Primate Pituitary via Common and Distinct Signaling Mechanisms
Authors: Luque Raúl M. , Córdoba-Chacón José , Gahete Manuel D. , Navarro Víctor M. , Tena-Sempere Manuel , Kineman Rhonda D. , Castaño Justo P.
Published: January 2011

Kisspeptins (Kps) have emerged as key players in the control of reproductive-axis function, in which they operate as primary regulators of hypothalamic GnRH release. In addition, recent data indicate that Kps can also directly act on the pituitary to stimulate LH and GH release in primary pituitary cell culture prepared from rats, cows, and sheep. We present herein evidence that Kps (specifically Kp-10) can also stimulate LH and GH release in primary pituitary cell cultures prepared from female baboons (Papio anubis), a species that more closely models human physiology. The stimulatory effect of Kp-10 on LH and GH release was dose and time dependent and enhanced the hormonal responses to their major regulators (GnRH for LH; GHRH/ghrelin for GH) without affecting the release of other pituitary hormones (TSH, FSH, ACTH, prolactin). Use of pharmacological intracellular signaling blockers indicated Kp-10 signals through phospholipase C, protein kinase C, MAPK, and intracellular Ca2+ mobilization, but not adenylyl cyclase, protein kinase A, extracellular Ca2+ influx (through L-type channels), or nitric oxide synthase, to stimulate both LH and GH release. Interestingly, blockade of mammalian target of rapamycin or phosphoinositol 3-kinase activity fully abolished the stimulatory effect of Kp-10 on LH but not GH release. Of note, estradiol enhanced the relative LH response to Kp-10, alone or in combination with GnRH. In sum, our data are the first to provide evidence that, in a primate model, there is a functional Kp-signaling system within the pituitary, which is dynamically regulated and may contribute to the direct control of gonadotropic and somatotropic axes.
Cell migration inDrosophilaoptic lobe neurons is controlled byeyeless/Pax6
Authors: Morante Javier , Erclik Ted , Desplan Claude
Published: January 2011

In the developing Drosophila optic lobe, eyeless, apterous and distal-less, three genes that encode transcription factors with important functions during development, are expressed in broad subsets of medulla neurons. Medulla cortex cells follow two patterns of cell movements to acquire their final position: first, neurons are arranged in columns below each neuroblast. Then, during pupation, they migrate laterally, intermingling with each other to reach their retinotopic position in the adult optic lobe. eyeless, which encodes a Pax6 transcription factor, is expressed early in progenitors and controls aspects of this cell migration. Its loss in medulla neurons leads to overgrowth and a failure of lateral migration during pupation. These defects in cell migration among medulla cortex cells can be rescued by removing DE-Cadherin. Thus, eyeless links neurogenesis and neuronal migration.
Dissolving the Patient Bermuda Triangle
Authors: Ahgren Bengt
Published: January 2011

The differentiation of roles, tasks and responsibilities in health care has gradually increased because of efforts to decentralize, specialize and professionalize our health-care systems. These development approaches can on the one hand be regarded as successful, although there is also a negativeflipside. Increased differentiation has concurrently fragmented the delivery of health care, which, in turn, can be divided into structural, clinical and cultural fragmentation. Patients are lost as a result of these conditions of fragmentation. This phenomenon can metaphorically be described as a'Patient Bermuda Triangle’. Actions to dissolve the Patient Bermuda Triangles are commonly termed ‘Integrated health care’, a global buzzword that includes integrated care pathway as well as other integrated health-care strategies. Moreover, integrated care is a means to an end: improved patient outcome. To achieve this, it is crucial to have necessary prerequisites in place: both functional and interactional conditions. This procedure seems to be an organic process where the stakeholders go through gradual changes until the optimum level of integration, as well as mutualistic interactions, is established. If these conditions are concealed or impossible to achieve, developmental work should be ended to avoid the evolvement of antagonistic relations between the stakeholders concerned. This state will likely establish a Patient Bermuda Triangle or reinforce an existing one.
Management challenges in care pathways: Conclusions of a qualitative study within 57 health-care organizations
Authors: Van Gerven E , Vanhaecht K , Deneckere S , Vleugels A , Sermeus W
Published: January 2011

The objectives of this paper are to study the aim of care pathways, who has decisional power concerning pathways, the actual follow-up, challenges in cross-boundary development and the support provided by information and communication technology (ICT). The study design included a qualitative study using semi-structured interviews with 88 care pathway coordinators and members of the executive board in 57 health-care organizations enrolled in the Belgian- Dutch Clinical Pathway Network. The study revealed that the most important objectives for introducing care pathways are more standardization and quality of care. In 76% of the interviewed organizations, pathways are discussed in a committee. There is a lack of continuous follow-up when care pathways are implemented. Pathways can facilitate cross-boundary care, but are a challenge because of the fragmentation within primary care. There is a need for more ICT support for care pathways. In conclusion, the executive board members and pathway coordinators state that clearly formulated objectives, a special steering committee, a clear follow-up to keep pathways alive, cross-boundary collaboration and ICT support are among the main challenges for the management of an organization.
Why pathways cannot be taken from the shelf
Authors: Vleugels Arthur
Published: January 2011

Clinical pathways are our most valuable and performant tool in managing health-care processes. Sloppiness and inaccuracy, in both definition and implementation, threaten to erode the concept and, thus, to undermine its power. Back to basics is not a plea for nostalgia, but for continuing consistently to design care according to a patient's needs, to focus on desired clinical outcomes and to anchor the care processes into the daily life of the health-care organization.
Development of a health promotion care pathway for adult hospital-based patients
Authors: Sinclair Janet , Haynes Charlotte , Lee Deborah
Published: January 2011

UK health policy highlights the importance of hospital patients being assessed for smoking, alcohol and obesity, and delivered health promotion for these risk factors; yet there is a paucity of guidance and research on health promotion care pathways that can inform the development of effective and efficient hospital health promotion services. Consultation with health-care professionals and public health experts was undertaken in order to develop a health promotion care pathway for smoking, alcohol and obesity. Eight adult wards piloted the care pathway. An audit of case-notes was completed for patients discharged from the pilot wards over 13 weeks. Patients were also followed up by survey for service and behaviour change feedback four weeks after discharge. In all, 56% of patients were assessed for lifestyle risk factors, 43% of whom were identified as having a risk factor and 13% were referred to specialists in delivering brief interventions (key workers). Seventy percent of patients referred to as key workers reported a positive change in their lifestyle. In conclusion, involvement of staff is essential in the development of the care pathway, ensuring that timely efficient processes are in place in order to affect the optimal outcome for patients in changing lifestyle behaviours.
Quantitative evaluation trial for functions included in currently available electronic clinical pathways products
Authors: Wakamiya Shunji , Yamauchi Kazunobu
Published: January 2011

No quantitative method is available to evaluate the functions of electronic clinical pathways embedded in electronic medical records. Therefore, we developed new evaluation sheets. The standard functions of electronic clinical pathways published in 2007 were modified to facilitate their quantification, and functions requested at Kawasaki Medical School Hospital were added when electronic medical records were introduced. Electronic clinical pathways products by four vendors were evaluated quantitatively and each function was given a weight according to its importance. Moreover, we compared this quantitative evaluation with the subjective evaluation of four staff from the Committee of Clinical Pathways. The results indicated that the implementation of many functions differed among the four vendors, and the quantitative evaluations were comparable. The weights of each function may differ among hospitals due to differences in their medical background, and further studies regarding weighting are necessary. It can be concluded that the method described in this study will be useful for quantitative evaluation of electronic clinical pathways functions.
Variation in thyroid function in subclinical hypothyroidism: importance of clinical follow-up and therapy
Authors: Karmisholt Jesper , Andersen Stig , Laurberg Peter
Published: January 2011

Subclinical hypothyroidism (SCH) is a common condition that is often observed without therapy. However, no evidence-based recommendation exists with regards to how patients with untreated SCH should be monitored.

Monitoring involves regular assessment of symptoms and signs of hypothyroidism (HYPO) and biochemical tests of thyroid function. An important question when repeated tests of thyroid function are performed is how large a difference in test results is needed to be confident that the change is real and not just due to chance variation.

Recent data show that the least significant difference between two tests in SCH is 40% for TSH and 15% for free thyroxine and free triiodothyronine, with 90% confidence. Furthermore, monitoring has to be based on biochemical function testing because serial evaluation of symptoms and signs related to HYPO is rather insensitive in detecting worsening of thyroid insufficiency.

When the presence of thyroid peroxidase auto-antibodies (TPO-Ab) in serum has been demonstrated, repeated measurements do not add much useful information in the monitoring of individual subclinical hypothyroid patients, as levels of TPO-Ab vary in parallel with TSH in these patients.

Lastly, we discuss how differences in the monitoring procedure influence the diagnostic outcome, and we suggest a follow-up approach for untreated subclinical hypothyroid patients.
Trophoblast stem cell marker gene expression in inner cell mass-derived cells from parthenogenetic equine embryos
Authors: Desmarais Joëlle A , Demers Simon-Pierre , Suzuki Joao , Laflamme Simon , Vincent Patrick , Laverty Sheila , Smith Lawrence C
Published: January 2011

Although putative horse embryonic stem (ES)-like cell lines have been obtained recently fromin vivo-derived embryos, it is currently not known whether it is possible to obtain ES cell (ESC) lines from somatic cell nuclear transfer (SCNT) and parthenogenetic (PA) embryos. Our aim is to establish culture conditions for the derivation of autologous ESC lines for cell therapy studies in an equine model. Our results indicate that both the use of early-stage blastocysts with a clearly visible inner cell mass (ICM) and the use of pronase to dissect the ICM allow the derivation of a higher proportion of primary ICM outgrowths from PA and SCNT embryos. Primary ICM outgrowths express the molecular markers of pluripotency POU class 5 homeobox 1 (POU5F1) and (sex determining region-Y)-box2 (SOX2), and in some cases,NANOG. Cells obtained after the passages of PA primary ICM outgrowths display alkaline phosphatase (AP) activity andPOU5F1,SOX2, caudal-related homeobox-2 (CDX2) and eomesodermin (EOMES) expression, but may loseNANOG. Cystic embryoid body-like structures expressingPOU5F1,CDX2andEOMESwere produced from these cells. Immunohistochemical analysis of equine embryos reveals the presence of POU5F1 in trophectoderm, primitive endoderm and ICM. These results suggest that cells obtained after passages of primary ICM outgrowths are positive for trophoblast stem cell markers while expressingPOU5F1and displaying AP activity. Therefore, these cells most likely represent trophoblast cells rather than true ESCs. This study represents an important first step towards the production of autologous equine ESCs for pre-clinical cell therapy studies on large animal models.
Isolation and Distribution of Bacterial Flora in Farmed Rainbow Trout from Mexico
Authors: Salgado-Miranda Celene , Palomares Elizabeth , Jurado Mirsam , Marín Aída , Vega Fernando , Soriano-Vargas Edgardo
Published: January 2011

Trout farming is a growing aquaculture industry in Mexico, with stock mainly supplied by the importation of eyed eggs. The aim of the present study was to determine the frequency of bacterial isolations in farmed rainbow trout Oncorhynchus mykiss from Mexico. Sixty-five farms distributed among seven states of Mexico were included in the study. Individual samples from gills, liver, spleen, intestine, and kidney were obtained from 563 apparently healthy fish. In total, 371 bacterial isolates were recovered from sampled fish; isolates of the genera Aeromonas, Edwardsiella, Enterobacter, Escherichia, Klebsiella, Plesiomonas, Pseudomonas, and Yersinia were identified. Aeromonads were the most frequently isolated bacteria. Renibacterium salmoninarum was not isolated from any of the sampled fish. Our results showed the presence of bacteria that are potential pathogens of both rainbow trout and humans.
Asian Fish Tapeworm Bothriocephalus acheilognathi in the Desert Southwestern United States
Authors: Archdeacon Thomas P. , Iles Alison , Kline Jason S. , Bonar Scott A.
Published: January 2011

The Asian fish tapeworm Bothriocephalus acheilognathi (Cestoda: Bothriocephalidea) is an introduced fish parasite in the southwestern United States and is often considered a serious threat to native desert fishes. Determining the geographic distribution of nonnative fish parasites is important for recovery efforts of native fishes. We examined 1,140 individuals belonging to nine fish species from southwestern U.S. streams and springs between January 2005 and April 2007. The Asian fish tapeworm was present in the Gila River, Salt River, Verde River, San Pedro River, Aravaipa Creek, and Fossil Creek, Arizona, and in Lake Tuendae at Zzyzx Springs and Afton Canyon of the Mojave River, California. Overall prevalence of the Asian fish tapeworm in Arizona fish populations was 19% (range = 0–100%) and varied by location, time, and fish species. In California, the prevalence, abundance, and intensity of the Asian fish tapeworm in Mohave tui chub Gila bicolor mohavensis were higher during warmer months than during cooler months. Three new definitive host species—Yaqui chub G. purpurea, headwater chub G. nigra, and longfin dace Agosia chrysogaster—were identified. Widespread occurrence of the Asian fish tapeworm in southwestern U.S. waters suggests that the lack of detection in other systems where nonnative fishes occur is due to a lack of effort as opposed to true absence of the parasite. To limit further spread of diseases to small, isolated systems, we recommend treatment for both endo- and exoparasites when management actions include translocation of fishes.
Effectiveness of Aquaflor (50% Florfenicol) to Control Mortality Associated with Streptococcus iniae in Freshwater-Reared Subadult Sunshine Bass
Authors: Bowker James D. , Ostland Vaughn E. , Carty Daniel , Bowman Molly P.
Published: January 2011

We conducted a field trial to evaluate the effectiveness of Aquaflor (50% florfenicol) for controlling mortality associated with Streptococcus iniae in freshwater-reared subadult sunshine bass (female white bass Morone chrysops × male striped bass M. saxatilis). Bacterial samples collected from moribund fish representing a reference population were presumptively identified microbiologically and were later confirmed to be S. iniae by biochemical characterization and polymerase chain reaction. The trial comprised a 1-d acclimation period, 10-d treatment period, and 14-d posttreatment period. During the treatment period, Aquaflor-medicated feed was administered to treated tanks (N = 3) at a target dose of 10 mg of florfenicol·kg of fish−1·d−1, and nonmedicated feed was administered to control tanks (N = 3). At the end of the posttreatment period, mean (±SD) cumulative mortality in treated tanks (9 ± 11%) was significantly (P = 0.040) less than that in control tanks (52 ± 13%). Analysis of medicated feed samples revealed that treated tanks had received an actual dose of 8.3 mg florfenicol·kg fish−1·d−1 (83% of target). No florfenicol was detected in control feed samples. Although the actual florfenicol dose administered to treated tanks was less than the target dose, the trial was accepted by the U.S. Food and Drug Administration Center for Veterinary Medicine as demonstrating the efficacy of Aquaflor to control mortality associated with S. iniae in cultured sunshine bass populations.
Effect of a Mixed Herb—Enriched Diet on the Innate Immune Response and Disease Resistance of Paralichthys olivaceus against Philasterides dicentrarchi Infection
Authors: Harikrishnan Ramasamy , Balasundaram Chellam , Kim Man-Chul , Kim Ju-Sang , Han Yong-Jae , Heo Moon-Soo
Published: January 2011

We investigated the effect of a mixed herb—enriched diet obtained from pomegranate Punica granatum, Dalmatian chrysanthemum Chrysanthemum cinerariaefolium, and mastic-leaved prickly-ash Zanthoxylum schinifolium on innate immune mechanisms (e.g., phagocytosis activity, respiratory burst activity, alternative complement activity, lysozyme activity, and disease resistance) of olive flounder Paralichthys olivaceus against the scuticociliate Philasterides dicentrarchi. All experimental groups were challenged with P. dicentrarchi (1 × 105 ciliates/mL) through intraperitoneal administration of the pathogen (50 μL) on day 1. On day 7, the infected groups were fed 0, 5, 50, and 100 mg/kg of the enriched diets. The innate immune parameters, cumulative mortality, and relative percent survival (RPS) were assessed at weeks 1, 2, 3, and 4. Administration of 50 or 100 mg/kg of the herbal-enriched diet enhanced immunity throughout the experimental period. However, at the 5-mg/kg dosage, the enriched diet did not enhance the innate immune estimates at any time. At doses of 50 and 100 mg/kg, administration of the diet preceding the challenge with P. dicentrarchi decreased the percentage cumulative mortality in the experimental groups and thereby increased RPS values. This study reports that administration of 50 or 100 mg/kg mixed herbal—enriched diet could positively influence the innate immune response to P. dicentrarchi and enhance the health status of olive flounder with respect to this microbe.
The Relationship between Adirondack Lake pH and Levels of Mercury in Yellow Perch
Authors: Brown Donald , Goncharov Alexey , Paul Eric , Simonin Howard , Carpenter David O.
Published: January 2011

Levels of total mercury in yellow perch Perca flavescens from Adirondack lakes were studied in relation to characteristics of the lakes to determine why some lakes had fish with higher concentrations of mercury. Almost all mercury in fish is in the form of methylmercury, which can pose significant health hazards to humans who consume such fish. Fish mercury concentrations and water chemistry data were analyzed from eight Adirondack lakes. Four lakes (Halfmoon Lake, Sand Pond, Rock Pond, and Upper Sister Lake) had pH values of less than 5.0. Four other lakes (Lake Adirondack, Kings Flow, Harris Lake, and Lake Kushaqua) had pH values of more than 7.0. The acidic lakes also had high levels of aluminum and low acid-neutralizing capacity relative to the neutral lakes. Yellow perch (n = 100) from the acidic lakes had significantly higher levels of mercury than did those (n = 102) from the neutral lakes (P < 0.001), and the total mercury concentration increased with both length and weight of the fish. We conclude that the pH of the lake water is a major factor in determining the concentration of methylmercury in yellow perch.