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A Universidade de Adelaide é uma instituição de ensino superior australiana fundada em 1874. É a terceira mais antiga universidade da Austrália.

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Long-term outcomes in revision powered endoscopic dacryocystorhinostomy

Ali, M.J.; Psaltis, A.J.; Wormald, P.J.
Fonte: Wiley-Blackwell Publicador: Wiley-Blackwell
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
Abstract not available; Mohammad Javed Ali, Alkis James Psaltis, and Peter John Wormald

The effect of meteorological variables on the transmission of hand, foot and mouth disease in four major cities of Shanxi province, China: a time series data analysis (2009-2013)

Wei, J.; Hansen, A.; Liu, Q.; Sun, Y.; Weinstein, P.; Bi, P.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2015 EN
Increased incidence of hand, foot and mouth disease (HFMD) has been recognized as a critical challenge to communicable disease control and public health response. This study aimed to quantify the association between climate variation and notified cases of HFMD in selected cities of Shanxi Province, and to provide evidence for disease control and prevention. Meteorological variables and HFMD cases data in 4 major cities (Datong, Taiyuan, Changzhi and Yuncheng) of Shanxi province, China, were obtained from the China Meteorology Administration and China CDC respectively over the period 1 January 2009 to 31 December 2013. Correlations analyses and Seasonal Autoregressive Integrated Moving Average (SARIMA) models were used to identify and quantify the relationship between the meteorological variables and HFMD. HFMD incidence varied seasonally with the majority of cases in the 4 cities occurring from May to July. Temperatures could play important roles in the incidence of HFMD in these regions. The SARIMA models indicate that a 1° C rise in average, maximum and minimum temperatures may lead to a similar relative increase in the number of cases in the 4 cities. The lag times for the effects of temperatures were identified in Taiyuan, Changzhi and Yuncheng. The numbers of cases were positively associated with average and minimum temperatures at a lag of 1 week in Taiyuan...

The prevalence of co-prescription of clinically relevant CYP enzyme inhibitor and substrate drugs in community-dwelling elderly Australians

Kerr, K.P.; Mate, K.E.; Magin, P.J.; Marley, J.; Stocks, N.P.; Disler, P.; Pond, C.D.
Fonte: Wiley-Blackwell Publicador: Wiley-Blackwell
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
WHAT IS KNOWN AND OBJECTIVE: The elderly are at increased risk of adverse effects resulting from drug interactions due to decreased drug clearance and polypharmacy. This study examines the prevalence of the co-administration of clinically relevant cytochrome P450 (CYP) enzyme inhibitors with drugs that are substrates for these enzymes, in the community-dwelling elderly in Australia. METHODS: Participants aged 75 years or older (n = 1045) were recruited via their general practitioners at four Australian sites (Newcastle, Sydney, Melbourne and Adelaide). A research nurse visited the home of each patient to compile a list of all prescription medications (including doses) currently used by the patient, and to complete assessments for depression, quality of life and cognitive status. The medication data were searched for the co-prescription of clinically relevant CYP inhibitor and corresponding substrate drugs. RESULTS AND DISCUSSION: Potentially inappropriate CYP inhibitor-substrate combinations were found in 6·2% (65/1045) of patients. These patients were on significantly more medications (6·1 ± 3·0 vs. 3·9 ± 2·5; P = 0·001) and had a significantly lower physical quality of life (P = 0·047) than those who were not on any CYP inhibitor-substrate combinations. The most commonly prescribed inhibitor-substrate combinations involved the CYP 3A4 inhibitors...

Death adder envenoming causes neurotoxicity not reversed by antivenom - Australian snakebite project (ASP-16)

Johnston, C.I.; O'Leary, M.A.; Brown, S.G.A.; Currie, B.J.; Halkidis, L.; Whitaker, R.; Close, B.; Isbister, G.K.; Nagree, Y.; Ker, F.; Greene, S.; Taylor, M.; Macrokanis, C.; Wilke, G.; Coulson, A.; Barnes, C.; Bonni, R.; Whitake, R.; Halkidis, L.; Isbis
Fonte: PLoS Publicador: PLoS
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
BACKGROUND: Death adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment. METHODOLOGY/PRINCIPAL FINDINGS: Definite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5-74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5-15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients...

B-Type natriuretic peptide suppression of neutrophil superoxide generation: mechanistic studies in normal subjects

Liu, S.; Ngo, D.T.; Stewart, S.; Horowitz, J.D.; Chirkov, Y.Y.
Fonte: Wiley-Blackwell Publicador: Wiley-Blackwell
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
Many acute cardiovascular disease states are associated with neutrophil infiltration of myocardium and subsequent release of superoxide (O2 (-) ) and myeloperoxidase (MPO), which contribute to inflammatory reactions. B-Type natriuretic peptide (BNP) is known to exert anti-inflammatory and antifibrotic effects, but it is not known whether these may include interactions with neutrophils. In neutrophils isolated from 20 healthy subjects, we assessed the effect of BNP on the 'neutrophil burst' (O2 (-) production and MPO release) stimulated by phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP), respectively. Effects of BNP on cGMP accumulation, and the effects of the cell-permeable cGMP analogue 8-(4-chlorophenylthio) guanosine-cGMP (8-p-CPT-cGMP) and protein kinase G (PKG) inhibition with KT5823 on the neutrophil-BNP interaction were also evaluated. B-Type natriuretic peptide suppressed O2 (-) release from neutrophils by 23 ± 6% (P < 0.001) and 24 ± 8% (P < 0.05) following PMA and fMLP stimulation, respectively. Although BNP did not significantly increase cGMP formation, 8-p-CPT-cGMP suppressed both PMA- and fMLP-induced neutrophil O2 (-) release by 16% and 28%, respectively (P < 0.05). The PKG inhibitor KT5823 attenuated the effects of BNP on both fMLP- and PMA-associated O2 (-) production. Neither BNP nor 8-p-CPT-cGMP significantly affected MPO release from neutrophils. Suppression of O2 (-) release from neutrophils by BNP may contribute to its anti-inflammatory and antifibrotic actions.; Saifei Liu...

Predicting unprecedented dengue outbreak using imported cases and climatic factors in Guangzhou, 2014

Sang, S.; Gu, S.; Bi, P.; Yang, W.; Yang, Z.; Xu, L.; Yang, J.; Liu, X.; Jiang, T.; Wu, H.; Chu, C.; Liu, Q.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2015 EN
INTRODUCTION: Dengue is endemic in more than 100 countries, mainly in tropical and subtropical regions, and the incidence has increased 30-fold in the past 50 years. The situation of dengue in China has become more and more severe, with an unprecedented dengue outbreak hitting south China in 2014. Building a dengue early warning system is therefore urgent and necessary for timely and effective response. METHODOLOGY AND PRINCIPAL FINDINGS: In the study we developed a time series Poisson multivariate regression model using imported dengue cases, local minimum temperature and accumulative precipitation to predict the dengue occurrence in four districts of Guangzhou, China. The time series data were decomposed into seasonal, trend and remainder components using a seasonal-trend decomposition procedure based on loess (STL). The time lag of climatic factors included in the model was chosen based on Spearman correlation analysis. Autocorrelation, seasonality and long-term trend were controlled in the model. A best model was selected and validated using Generalized Cross Validation (GCV) score and residual test. The data from March 2006 to December 2012 were used to develop the model while the data from January 2013 to September 2014 were employed to validate the model. Time series Poisson model showed that imported cases in the previous month...

A systematic review of conversion from calcineurin inhibitor to mammalian target of rapamycin inhibitors for maintenance immunosuppression in kidney transplant recipients

Lim, W.H.; Eris, J.; Kanellis, J.; Pussell, B.; Wiid, Z.; Witcombe, D.; Russ, G.R.
Fonte: Wiley Publicador: Wiley
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
This was a systematic review of randomized controlled trials comparing delayed conversion of mammalian target of rapamycin inhibitors (mTORi) for calcineurin inhibitors (CNIs) versus CNI continuation in kidney transplantation. Databases (2000-2012) and conference abstracts (2009-2012) were searched giving a total of 29 trials. Outcomes analyzed included GFR, graft loss, rejection and adverse events and were expressed as weighted mean differences (WMDs) or as risk ratios (RRs). Patients converted to mTORi up to 1 year posttransplant in intention-to-treat analysis had higher GFR compared with those remaining on CNI (WMD 0.28 mL/min/1.73 m(2) , 95% confidence interval [CI] 0.21-0.36; I(2)  = 68%, p < 0.001). Stratifying trials by time posttransplant or type of mTORi did not change the overall heterogeneity. For on-treatment population, mTORi was associated with higher GFR (14.21 mL/min/1.73 m(2) , 10.34-18.08; I(2)  = 0%, p = 0.970) 2-5 years posttransplant. The risk of rejection at 1 year was higher in mTORi trials (RR 1.72, 1.34-2.22; I(2)  = 12%, p = 0.330). Discontinuation secondary to adverse events was more common in patients on mTORi, whereas the incidence of skin cancers and cytomegalovirus infection was lower in patients on mTORi. Conversion from CNI to mTORi is associated with short-term improvements in GFR in a number of studies but longer-term follow-up data of graft and patient survival are required.; W. H. Lim...

Setting research priorities for preconception care in low- and middle-income countries: aiming to reduce maternal and child mortality and morbidity

Dean, S.; Rudan, I.; Althabe, F.; Webb Girard, A.; Howson, C.; Langer, A.; Lawn, J.; Reeve, M.E.; Teela, K.C.; Toledano, M.; Venkatraman, C.M.; Belizan, J.M.; Car, J.; Chan, K.Y.; Chatterjee, S.; Chitekwe, S.; Doherty, T.; Donnay, F.; Ezzati, M.; Humayun,
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
Sohni Dean, ... Zohra S. Lassi, ... et al.

Relationship between plasma, atrial and ventricular perhexiline concentrations in humans: insights into factors affecting myocardial uptake

Drury, N.E.; Licari, G.; Chong, C.R.; Howell, N.J.; Frenneaux, M.P.; Horowitz, J.D.; Pagano, D.; Sallustio, B.C.
Fonte: Wiley Publicador: Wiley
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
AIM: Little is known regarding the steady-state uptake of drugs into the human myocardium. Perhexiline is a prophylactic anti-anginal drug which is increasingly also used in the treatment of heart failure and hypertrophic cardiomyopathy. We explored the relationship between plasma perhexiline concentrations and its uptake into the myocardium. METHODS: Blood, right atrium ± left ventricle biopsies were obtained from patients treated with perhexiline for a median of 8.5 days before undergoing coronary surgery in the perhexiline arm of a randomized controlled trial. Perhexiline concentrations in plasma and heart tissue were determined by HPLC. RESULTS: Atrial biopsies were obtained from 94 patients and ventricular biopsies from 28 patients. The median plasma perhexiline concentration was within the therapeutic range at 0.24 mg l⁻¹ (IQR 0.12-0.44), the median atrial concentration was 6.02  mg kg⁻¹ (IQR 2.70-9.06) and median ventricular concentration was 10.0 mg kg⁻¹ (IQR 5.76-13.1). Atrial (r² = 0.76) and ventricular (r² = 0.73) perhexiline concentrations were closely and directly correlated with plasma concentrations (both P < 0.001). The median atrial : plasma ratio was 21.5 (IQR 18.1-27.1), ventricular : plasma ratio was 34.9 (IQR 24.5-55.2) and ventricular : atrial ratio was 1.67 (IQR 1.39-2.22). Using multiple regression...

Genetic heritage of the balto-slavic speaking populations: a synthesis of autosomal, mitochondrial and Y-chromosomal data

Kushniarevich, A.; Utevska, O.; Chuhryaeva, M.; Agdzhoyan, A.; Dibirova, K.; Uktveryte, I.; Möls, M.; Mulahasanovic, L.; Pshenichnov, A.; Frolova, S.; Shanko, A.; Metspalu, E.; Reidla, M.; Tambets, K.; Tamm, E.; Koshel, S.; Zaporozhchenko, V.; Atramentov
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2015 EN
The Slavic branch of the Balto-Slavic sub-family of Indo-European languages underwent rapid divergence as a result of the spatial expansion of its speakers from Central-East Europe, in early medieval times. This expansion–mainly to East Europe and the northern Balkans–resulted in the incorporation of genetic components from numerous autochthonous populations into the Slavic gene pools. Here, we characterize genetic variation in all extant ethnic groups speaking Balto-Slavic languages by analyzing mitochondrial DNA (n = 6,876), Y-chromosomes (n = 6,079) and genome-wide SNP profiles (n = 296), within the context of other European populations. We also reassess the phylogeny of Slavic languages within the Balto-Slavic branch of Indo-European. We find that genetic distances among Balto-Slavic populations, based on autosomal and Y-chromosomal loci, show a high correlation (0.9) both with each other and with geography, but a slightly lower correlation (0.7) with mitochondrial DNA and linguistic affiliation. The data suggest that genetic diversity of the present-day Slavs was predominantly shaped in situ, and we detect two different substrata: ‘central-east European’ for West and East Slavs, and ‘south-east European’ for South Slavs. A pattern of distribution of segments identical by descent between groups of East-West and South Slavs suggests shared ancestry or a modest gene flow between those two groups...

Loss of glucocorticoid receptor from pro-inflammatory T cells after lung transplant

Hodge, G.; Hodge, S.; Holmes-Liew, C.L.; Reynolds, P.N.; Holmes, M.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
Abstract not available; Greg Hodge, Sandra Hodge, Chien Li Holmes-Liew, Paul N. Reynolds, and Mark Holmes

Clinical effects and antivenom dosing in brown snake (Pseudonaja spp.) envenoming - Australian snakebite project (ASP-14)

Allen, G.E.; Brown, S.G.A.; Buckley, N.A.; O'Leary, M.A.; Page, C.B.; Currie, B.J.; White, J.; Isbister, G.K.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
BACKGROUND: Snakebite is a global health issue and treatment with antivenom continues to be problematic. Brown snakes (genus Pseudonaja) are the most medically important group of Australian snakes and there is controversy over the dose of brown snake antivenom. We aimed to investigate the clinical and laboratory features of definite brown snake (Pseudonaja spp.) envenoming, and determine the dose of antivenom required. METHODS AND FINDING: This was a prospective observational study of definite brown snake envenoming from the Australian Snakebite Project (ASP) based on snake identification or specific enzyme immunoassay for Pseudonaja venom. From January 2004 to January 2012 there were 149 definite brown snake bites [median age 42 y (2-81 y); 100 males]. Systemic envenoming occurred in 136 (88%) cases. All envenomed patients developed venom induced consumption coagulopathy (VICC), with complete VICC in 109 (80%) and partial VICC in 27 (20%). Systemic symptoms occurred in 61 (45%) and mild neurotoxicity in 2 (1%). Myotoxicity did not occur. Severe envenoming occurred in 51 patients (38%) and was characterised by collapse or hypotension (37), thrombotic microangiopathy (15), major haemorrhage (5), cardiac arrest (7) and death (6). The median peak venom concentration in 118 envenomed patients was 1.6 ng/mL (Range: 0.15-210 ng/mL). The median initial antivenom dose was 2 vials (Range: 1-40) in 128 patients receiving antivenom. There was no difference in INR recovery or clinical outcome between patients receiving one or more than one vial of antivenom. Free venom was not detected in 112/115 patients post-antivenom with only low concentrations (0.4 to 0.9 ng/ml) in three patients. CONCLUSIONS: Envenoming by brown snakes causes VICC and over a third of patients had serious complications including major haemorrhage...

Double island pedicle or V-Y flap repair for partial-thickness combined defects of the cutaneous and mucosal lip

Huilgol, S.C.; Ma, J.H.Y.; Hills, R.J.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
BACKGROUND: Removal of skin cancer at or near the vermilion border may result in a partial-thickness combined cutaneous and mucosal lip defect for which repair has potential for poor cosmetic and functional outcomes. OBJECTIVE: We sought to describe the closure and results from repair of combined lip defects using 2 island pedicle or V-Y flaps, 1 for the cutaneous lip and 1 for the mucosa. METHODS: A retrospective review of all patients with combined defects of the lip who underwent double island pedicle or V-Y flap repair from June 2008 to December 2013 was performed. RESULTS: Ten patients (6 female, 4 male; ages 35-89 years, mean age 60 years) had defects on the upper lip in 8 cases and on the lower lip in 2 cases. Follow-up was for 3 months or longer with good or excellent outcomes in all cases. LIMITATIONS: This was a nonrandomized, unblinded clinical case series with a limited sample size. CONCLUSION: Double island pedicle or V-Y flap repair is an elegant closure with good to excellent results and may avoid potential problems inherent in other repair options.; Shyamala C. Huilgol, Joyce H. Y. Ma, and Russell J. Hills

HENMT1 and piRNA stability are required for adult male germ cell transposon repression and to define the spermatogenic program in the mouse

Lim, S.L.; Qu, Z.P.; Kortschak, R.D.; Lawrence, D.M.; Geoghegan, J.; Hempfling, A.L.; Bergmann, M.; Goodnow, C.C.; Ormandy, C.J.; Wong, L.; Mann, J.; Scott, H.S.; Jamsai, D.; Adelson, D.L.; O'Bryan, M.K.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2015 EN
piRNAs are critical for transposable element (TE) repression and germ cell survival during the early phases of spermatogenesis, however, their role in adult germ cells and the relative importance of piRNA methylation is poorly defined in mammals. Using a mouse model of HEN methyltransferase 1 (HENMT1) loss-of-function, RNA-Seq and a range of RNA assays we show that HENMT1 is required for the 2' O-methylation of mammalian piRNAs. HENMT1 loss leads to piRNA instability, reduced piRNA bulk and length, and ultimately male sterility characterized by a germ cell arrest at the elongating germ cell phase of spermatogenesis. HENMT1 loss-of-function, and the concomitant loss of piRNAs, resulted in TE de-repression in adult meiotic and haploid germ cells, and the precocious, and selective, expression of many haploid-transcripts in meiotic cells. Precocious expression was associated with a more active chromatin state in meiotic cells, elevated levels of DNA damage and a catastrophic deregulation of the haploid germ cell gene expression. Collectively these results define a critical role for HENMT1 and piRNAs in the maintenance of TE repression in adult germ cells and setting the spermatogenic program.; Shu Ly Lim, Zhi Peng Qu, R. Daniel Kortschak...

Neuropsychologic outcomes in patients treated for complex maxillofacial trauma

Snell, B.J.; Roberts, R.M.; Anderson, P.; David, D.J.
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
Complex fractures of the craniofacial skeleton are caused most commonly, in Australia, by motor vehicle accidents, falls, and interpersonal violence. Significant force is required to fracture the facial skeleton, and the long-term effect these forces have on higher brain function is unclear. The study aim was to assess long-term neuropsychologic changes associated with complex fractures of the facial skeleton. Patients managed for complex fractures of the facial skeleton by the Australian Craniofacial Unit, South Australia, between 2002 and 2011, with at least 1-year follow-up, were assessed using the European Brain Injury Questionnaire. This questionnaire has previously published control data to which results were compared. Of the 2077 patients treated for facial fractures, 46 were identified as having complex fractures of the facial skeleton. Of the 46 patients, 13 were able to be contacted and assessed using the European Brain Injury Questionnaire. Changes in personality and ability to socialize and undertake executive function were noted in approximately 30% of the patients. In addition, approximately 50% of the patients' family members reported significant changes in the patients' life after the accident, yet this was only recognized by approximately 30% of the patients. This study shows that...

Direct endoscopic jejunosotomy for the administration of levodopa-carbidopa intestinal gel in Parkinson's disease

Kimber, T.E.; Schoeman, M.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
Thomas E. Kimber, Mark Schoeman; Letter to the Editor

Interferon-gamma modification of mesenchymal stem cells: implications of autologous and allogeneic mesenchymal stem cell therapy in allotransplantation

Sivanathan, K.N.; Gronthos, S.; Rojas-Canales, D.; Thierry, B.; Coates, P.T.
Fonte: Springer Publicador: Springer
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
Bone marrow-derived mesenchymal stem cells (MSC) have unique immunomodulatory and reparative properties beneficial for allotransplantation cellular therapy. The clinical administration of autologous or allogeneic MSC with immunosuppressive drugs is able to prevent and treat allograft rejection in kidney transplant recipients, thus supporting the immunomodulatory role of MSC. Interferon-gamma (IFN-γ) is known to enhance the immunosuppressive properties of MSC. IFN-γ preactivated MSC (MSC-γ) directly or indirectly modulates T cell responses by enhancing or inducing MSC inhibitory factors. These factors are known to downregulate T cell activation, enhance T cell negative signalling, alter T cells from a proinflammatory to an anti-inflammatory phenotype, interact with antigen-presenting cells and increase or induce regulatory cells. Highly immunosuppressive MSC-γ with increased migratory and reparative capacities may aid tissue repair, prolong allograft survival and induce allotransplant tolerance in experimental models. Nevertheless, there are contradictory in vivo observations related to allogeneic MSC-γ therapy. Many studies report that allogeneic MSC are immunogenic due to their inherent expression of major histocompatibility (MHC) molecules. Enhanced expression of MHC in allogeneic MSC-γ may increase their immunogenicity and this can negatively impact allograft survival. Therefore...

Multipotent cell types in primary fibroblast cell lines used to clone pigs using somatic cell nuclear transfer

Harrison, S.J.; Beebe, L.F.S.; Vassiliev, I.; McIlfatrick, S.M.; Nottle, M.B.
Fonte: OMICS Publishing Group Publicador: OMICS Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //2015 EN
We have previously demonstrated that the use of porcine mesenchymal stem cells (MSCs) isolated from the bone marrow can increase the proportion of somatic cell nuclear transfer (SCNT) embryos that develop to the blastocyst stage compared with adult fibroblasts obtained from the same animal. The aim of the present study was to determine if MSCs are also present in primary cultures of adult fibroblasts which are commonly used for cloning live animals. To do this we chose a primary culture of adult fibroblasts that we had previously used to clone pigs. Single cell clones were isolated using low-density plating. After seven days of culture 63% of colonies displayed typical fibroblast morphology, while the remainder appeared cobblestone-like in appearance. Two of the 57 clones that displayed fibroblast morphology differentiated into adipocytes but not chondrocytes or osteocytes (uni-potent clones). Three of the 33 cobblestone-like clones differentiated into chondrocytes only, while 3 differentiated into adipocytes and chondrocytes but not osteocytes (bi-potent clones). One of the bi-potent cobblestone-like clones was then used for SCNT and in vitro development compared with a fibroblast-like clone which did not differentiate. Both cell types produced blastocysts at similar rates. In conclusion we have identified uni-potent and bi-potent cell types in primary cultures of adult fibroblasts used previously to clone live piglets.; Sharon J. Harrison...

Association of early and late maternal smoking during pregnancy with offspring body mass index at 4 to 5 years of age

Grzeskowiak, L.E.; Hodyl, N.A.; Stark, M.J.; Morrison, J.L.; Clifton, V.L.
Fonte: Cambridge University Press Publicador: Cambridge University Press
Tipo: Artigo de Revista Científica
Publicado em //2015 EN
The objective was to investigate the association between early and late maternal smoking during pregnancy on offspring body mass index (BMI). We undertook a retrospective cohort study using linked records from the Women's and Children's Health Network in South Australia. Among a cohort of women delivering a singleton, live-born infants between January 2000 and December 2005 (n=7658), 5961 reported not smoking during pregnancy, 297 reported quitting smoking during the first trimester of pregnancy, and 1400 reported continued smoking throughout pregnancy. Trained nurses measured the height and weight of the children at preschool visits in a state-wide surveillance programme. The main outcome measure was age- and sex-specific BMI z-score. At 4 to 5 years, mean (s.d.) BMI z-score was 0.40 (1.05), 0.60 (1.07) and 0.65 (1.18) in children of mothers who reported never smoking, quitting smoking and continued smoking during pregnancy, respectively. Compared with the group of non-smokers, both quitting smoking and continued smoking were associated with an increase in child BMI z-score of 0.15 (95% confidence interval: 0.01-0.29) and 0.21 (0.13-0.29), respectively. A significant dose-response relationship was also observed between the number of cigarettes smoked per day on average during the second half of pregnancy and the increase in offspring BMI z-score (P<0.001). In conclusion...

Copy number variants in patients with intellectual disability affect the regulation of ARX transcription factor gene

Ishibashi, M.; Manning, E.; Shoubridge, C.; Krecsmarik, M.; Hawkins, T.A.; Giacomotto, J.; Zhao, T.; Mueller, T.; Bader, P.I.; Cheung, S.W.; Stankiewicz, P.; Bain, N.L.; Hackett, A.; Reddy, C.C.S.; Mechaly, A.S.; Peers, B.; Wilson, S.W.; Lenhard, B.; Ball
Fonte: Springer Publicador: Springer
Tipo: Artigo de Revista Científica
Publicado em //2015 EN
Protein-coding mutations in the transcription factor-encoding gene ARX cause various forms of intellectual disability (ID) and epilepsy. In contrast, variations in surrounding non-coding sequences are correlated with milder forms of non-syndromic ID and autism and had suggested the importance of ARX gene regulation in the etiology of these disorders. We compile data on several novel and some already identified patients with or without ID that carry duplications of ARX genomic region and consider likely genetic mechanisms underlying the neurodevelopmental defects. We establish the long-range regulatory domain of ARX and identify its brain region-specific autoregulation. We conclude that neurodevelopmental disturbances in the patients may not simply arise from increased dosage due to ARX duplication. This is further exemplified by a small duplication involving a non-functional ARX copy, but with duplicated enhancers. ARX enhancers are located within a 504-kb region and regulate expression specifically in the forebrain in developing and adult zebrafish. Transgenic enhancer-reporter lines were used as in vivo tools to delineate a brain region-specific negative and positive autoregulation of ARX. We find autorepression of ARX in the telencephalon and autoactivation in the ventral thalamus. Fluorescently labeled brain regions in the transgenic lines facilitated the identification of neuronal outgrowth and pathfinding disturbances in the ventral thalamus and telencephalon that occur when arxa dosage is diminished. In summary...