7 research outputs found

    Growth and development are similar in VLBW children born appropriate and small for gestational age: an interim report on 97 preschool children

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    Aim: To investigate growth and development in a cohort of children born with very low birth weight (VLBW) treated at a single tertiary neonatal unit. Methods: We studied 97 children born between January 1995 and July 1997 with BW &lt;1,500 g. At follow-up (mean age 3.7 years) anthropometric data and data on neurological status, motor, speech and language development were collected. Small for gestational age (SGA) was defined as weight and/or length at birth &lt;10th percentile; shortness at follow-up was defined as height &lt;10th percentile. Results: Comparison was made between the appropriate for gestational age (AGA) (n = 46) and SGA (n = 51) groups. At follow-up, 23 AGA and 35 SGA children were short, had a smaller head circumference (-1.9 vs -0.8 SDS), were lighter at birth (BW -1.3 vs -0.7 SDS), and had a higher rate of broncho-pulmonary dysplasia (BPD) (28 vs 12); no differences in neonatal characteristics or neurological status were evident. A higher frequency of motor delay occurred in the 'short' group. Short children also had a smaller head circumference (HC) (-1.6 vs -0.7). Short SGA children had a higher frequency of BPD, smaller HC (-2.1 vs -1.0), and a slightly higher proportion of suspicious neurological findings, motor delay, and speech and language delay (n.s.). Conclusions: Preterm VLBW infants, whether AGA or SGA at birth, face the risk of being short at preschool age. Height outcome is probably influenced by postnatal factors. Our data also suggest that short stature is associated with developmental difficulties in this population.<br/

    Cognitive and psychosocial development of children with Pierre Robin sequence

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    Aim: It is unclear whether cognitive impairment in Pierre Robin sequence (PRS) results from a primary disturbance affecting both the brain and the mandible or from recurrent upper airway obstruction (UAO). If the latter were true, cognitive impairment should be preventable by early treatment of UAO. We wanted to determine the cognitive and psychosocial outcome of children with PRS treated with a new device aimed at relieving UAO in infancy (pre-epiglottic baton plate). Methods: Thirty-four children with PRS and 34 healthy controls aged 4-11 years completed the Kaufman-Assessment Battery for Children (K-ABC) and a self-concept inventory. Parents rated their children\u27s emotional and behavioural problems. Multi- and univariate analyses of covariance were performed, controlling for gender, age, parental education, family income and parental depression. Results: The cognitive development of the PR children was within the reference range. Compared to healthy children, however, the children with PRS performed significantly poorer. There were no significant differences concerning self-concept, emotional or behavioural problems. Conclusion: These children with non-syndromic PRS who had received treatment of UAO in infancy performed worse in the K-ABC. However, this did not reflect a major cognitive impairment. \ua9 2008 The Author(s)

    The Son and the other stars: Christology and cosmology in the imagination of C.S. Lewis

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    This dissertation treats the theory and practice of C. S. Lewis's theological imagination, focussing upon the imaginative use he made of his professional expertise in medieval and renaissance literature. Its approach is principally expository rather than an evaluative. Chapter One outlines the centrality of the imagination to a proper understanding of Lewis's works. Chapter Two examines Lewis's own theory of imagination and surveys how he practised it as a literary critic. We compare and contrast Lewis's theory and practice of imagination with that of his friend, the theologian, Austin Faffer. Chapter Three looks in more detail at Lewis's imaginative practice, in particular his fascination with the images supplied by the seven planets of the Ptolemaic cosmos, which he termed 'spiritual symbols of permanent value'. We analyse what he meant by 'sprit' and 'symbol'. Chapter Four introduces the main argument of the dissertation namely that these seven spiritual symbols structure the works for which Lewis is best known, the seven 'Chronicles of Narnia'. We claim to have uncovered the governing imaginative blueprint of the septet. We address Lewis's capacity for and interest in secrecy and consider why this planetary theme has remained hitherto undetected. In Chapters Five to Eleven we take the seven planets in turn and trace the use Lewis made of them through out his writings. We analyse the planetary symbolism undergirding each Chronicle and conclude each chapter with an exegesis of the Christological message of each book so understood. Chapter Twelve examines factors which motivated Lewis to focus his imaginative energies upon Ptolemaic cosmology and suggests one particular occasioning factor behind the composition of the Chronicles. In addition, we consider theological and pedagogical reasons why he kept silent about the planetary theme. We conclude by indicating certain consequences that our argument has for future readings of these seven works

    Breaking bad news in China the dilemma of patients&apos; autonomy and traditional norms. A first communication skills training for Chinese oncologists and caretakers

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    Objective Current practice of breaking bad news in China involves disclosure of information first to family members who then decide whether the patient should receive this information. Recently, however, patients&apos; right to be informed has been regulated by law. This represents a dilemma for oncologists who now have to balance traditional practice with new legal requirements. A communication skills training (CST) was developed for Chinese practice. It addresses this issue and may help participants find individual solutions within these conflicting requirements. Methods A first CST about breaking bad news took place at the Beijing Cancer Hospital, China, with 31 participants. We (i) assessed current practice, (ii) evaluated the workshop and (iii) self-assessed performance ratings about breaking bad news before and after the workshop with the help of questionnaires. Results (i) Participants stated that in most cases (78%), they inform family members first. Contrary to this practice, participants think that about 75% of patients would like to be informed first, independent of family. (ii) Overall, the workshop received a very good rating (M=1.2; scale between 1 and 6). (iii) After the workshop, the participants rated their performance significantly higher in all areas, for example, talking about diagnosis, prognosis and death with the patient and the family. Conclusions The CST showed high acceptance and led to significantly improved performance ratings of participating physicians in many areas. It helped participants deal with conflicting demands. For future trainings, further socio-cultural adaptations are needed. Obvious conflicts still exist and need to be resolved. Copyright (c) 2012 John Wiley &amp; Sons, Ltd.OncologyPsychologyPsychology, MultidisciplinarySocial Sciences, BiomedicalSCI(E)SSCI5ARTICLE51192-11952

    Burden of sequelae and healthcare resource utilization in the first year of life in infants born with congenital cytomegalovirus (cCMV) infection in Germany: A retrospective statutory health insurance claims database analysis

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    de Lepper M, Stephan A-J, Wölle R, et al. Burden of sequelae and healthcare resource utilization in the first year of life in infants born with congenital cytomegalovirus (cCMV) infection in Germany: A retrospective statutory health insurance claims database analysis. PLoS ONE . 2023;18(11): e0293869.BACKGROUND: Congenital cytomegalovirus (cCMV) infection can have a broad range of manifestations. This study aimed to assess cCMV-associated sequelae and healthcare resource utilization (HCRU) in infants during the first year of life in Germany.; METHODS: A retrospective, controlled cohort study using German claims data from the Institute for Applied Health Research Berlin (InGef) database was conducted. cCMV-associated sequelae and HCRU during the first year of life were assessed by matching (1:60) infants with at least one inpatient/outpatient cCMV diagnosis (ICD-10-GM: P35.1) ≤90 days after birth (cCMV90 cohort) and infants with at least one inpatient cCMV diagnosis plus specific sequelae ≤21 days after birth (cCMV21-S) to infants without cCMV or CMV (ICD-10-GM: B25) diagnosis (control group), respectively. Outcomes were analyzed during the first 365 days of life.; RESULTS: Between 2014-2018, we identified 54 newborns for cCMV90 and 24 newborns for cCMV21-S cohort. Compared to the 3,240 and 1,440 controls, respectively, more cCMV90 infants (83.3% vs. 41.9%, p<0.01) presented with at least one sequela during the first year of life, including intrauterine growth retardation (42.6% vs. 5.3%, p<0.01), sensorineural hearing loss (SNHL) to deafness (38.9% vs. 2.2%, p<0.01), and motor development disorders (33.3% vs. 10.9%, p<0.01). Further, 13.0% of cCMV90 infants (vs. 2.3%, p<0.01) suffered from visual impairment. In cCMV21-S cohort, intrauterine growth retardation (79.2% vs. 6.0%, p<0.01), prematurity (54.2% vs. 7.3%, p<0.01), and motor development disorders (50.0% vs. 11.0%, p<0.01) were the most frequent sequelae. Infants in the cCMV90 and cCMV21-S cohort had, on average, 7.3 times and 9.5 times more hospitalizations and 2.0 times and 2.1 times more outpatient physician visits than their respective controls (p<0.01). Hospitalized infants with cCMV stayed, on average, significantly longer in hospital compared to their controls (cCMV90 cohort: 30.3 days vs. 9.0 days, p<0.01; cCMV21-S cohort: 46.5 days vs. 9.3 days, p<0.01).; CONCLUSIONS: cCMV-infection shows a considerable disease and healthcare burden during the first year of life. More than 80% of the identified newborns with cCMV suffered from at least one associated sequela during the first year of life, including long-term sequelae such as SNHL (40%) and visual impairment (13%). Additional steps for prevention of cCMV infection and associated sequelae as well as a comprehensive monitoring of disease burden are needed. Copyright: © 2023 de Lepper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

    Molecular diagnosis of cutaneous leishmaniasis and species identification: Analysis of 122 biopsies with varied parasite index

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    Background: Cutaneous leishmaniasis is endemic in the Middle East and North Africa. Confirming the diagnosis histologically depends on amastigote identification, which varies significantly depending on the inoculum, strain type, host response and disease stage. Accurate histological diagnosis is mandatory for appropriate therapy. Methods: Skin biopsies from 122 patients from Lebanon, Syria and Saudi Arabia with clinical diagnosis of untreated leishmaniasis were reviewed and clinical data extracted. Cases were classified according to the modified Ridley's parasitic index. DNA was extracted from formalin-fixed paraffin-embedded blocks. Polymerase chain reaction (PCR) was performed using Leishmania-specific ribosomal internal transcribed spacer 1 (ITS1-PCR). Nested ITS1-PCR was performed on cases negative for conventional ITS1-PCR. ITS1-PCR amplicons were digested with HaeIII for subsequent restriction fragment length polymorphism (RFLP) subspeciation. Results: Of 122 cases, 54 (44.3percent) showed a parasitic index of 0-1+ (no unequivocal amastigotes). ITS1-PCR (conventional and nested) was positive for all cases as compared with negative control tissue. RFLP identified Leishmania tropica in all cases. Patients with clinically suspected leishmaniasis, whose skin biopsies failed to detect amastigotes represented 44.3percent of our cases. Conclusions: In this study, we describe a rapid and optimized protocol from DNA extraction to leishmaniasis subspeciation. ITS1-PCR showed high sensitivity and specificity in confirming clinically suspected cases. © 2011 John Wiley and Sons A-S.Al-Jawabreh A, 2006, ACTA TROP, V99, P55, DOI 10.1016-j.actatropica.2006.07.001; Ameen M, 2010, CLIN EXP DERMATOL, V35, P699, DOI 10.1111-j.1365-2230.2010.03851.x; Azmi K, 2010, TROP MED INT HEALTH, V15, P872, DOI 10.1111-j.1365-3156.2010.02551.x; BARKER DC, 1989, PARASITOLOGY, V99, pS125; Bensoussan E, 2006, J CLIN MICROBIOL, V44, P1435, DOI 10.1128-JCM.44.4.1435-1439.2006; Boggild AK, 2010, CLIN INFECT DIS, V50, pE1, DOI 10.1086-648730; BOOM R, 1990, J CLIN MICROBIOL, V28, P495; Castilho TM, 2003, J CLIN MICROBIOL, V41, P540, DOI 10.1128-JCM.41.2.540-546.2003; CUPOLILLO E, 1995, MOL BIOCHEM PARASIT, V73, P145, DOI 10.1016-0166-6851(95)00108-D; David CV, 2009, DERMATOL THER, V22, P491, DOI 10.1111-j.1529-8019.2009.01272.x; El Tai NO, 2000, T ROY SOC TROP MED H, V94, P575, DOI 10.1016-S0035-9203(00)90093-2; El Tai NO, 2001, EXP PARASITOL, V97, P35, DOI 10.1006-expr.2001.4592; FARAH FS, 1971, ARCH DERMATOL, V103, P467, DOI 10.1001-archderm.103.5.467; GOELZ SE, 1985, BIOCHEM BIOPH RES CO, V130, P118, DOI 10.1016-0006-291X(85)90390-0; Goto H, 2010, EXPERT REV ANTI-INFE, V8, P419, DOI [10.1586-eri.10.19, 10.1586-ERI.10.19]; Huijsmans Cornelis Jj, 2010, BMC Res Notes, V3, P239, DOI 10.1186-1756-0500-3-239; Kazemi-Rad E, 2008, IRAN J PUBLIC HEALTH, V37, P54; LASKAY T, 1995, T ROY SOC TROP MED H, V89, P273, DOI 10.1016-0035-9203(95)90537-5; Meredith S. E. O., 1993, Archives de l'Institut Pasteur de Tunis, V70, P419; Minodier P, 1997, J CLIN MICROBIOL, V35, P2551; Momeni AZ, 1996, ARCH DERMATOL, V132, P198, DOI 10.1001-archderm.132.2.198; Mugasa CM, 2010, PARASITE VECTOR, V3, DOI 10.1186-1756-3305-3-13; Nasereddin A, 2008, J CLIN MICROBIOL, V46, P2848, DOI 10.1128-JCM.00951-08; Osman OF, 1997, J CLIN MICROBIOL, V35, P2454; RIDLEY DS, 1983, J PATHOL, V141, P83, DOI 10.1002-path.1711410109; RODGERS MR, 1990, EXP PARASITOL, V71, P267, DOI 10.1016-0014-4894(90)90031-7; Safaei A, 2002, DERMATOLOGY, V205, P18, DOI 10.1159-000063150; Salman SM, 1999, CLIN DERMATOL, V17, P291, DOI 10.1016-S0738-081X(99)00047-4; Scarisbrick J J, 2006, Travel Med Infect Dis, V4, P14, DOI 10.1016-j.tmaid.2004.11.002; Schallig HDFH, 2002, TROP MED INT HEALTH, V7, P641, DOI 10.1046-j.1365-3156.2002.00911.x; Schonian G, 2008, TRENDS PARASITOL, V24, P135, DOI 10.1016-j.pt.2007.12.006; Schonian G, 2003, DIAGN MICR INFEC DIS, V47, P349, DOI 10.1016-S0732-8893(03)00093-2; SHIBATA DK, 1988, J EXP MED, V167, P225, DOI 10.1084-jem.167.1.225; Singh S, 2005, EXPERT REV MOL DIAGN, V5, P251, DOI 10.1586-14737159.5.2.251; Spanakos G, 2008, T ROY SOC TROP MED H, V102, P46, DOI 10.1016-j.trstmh.2007.05.019; VANEYS GJJM, 1992, MOL BIOCHEM PARASIT, V51, P133; Vega-Lopez F, 2003, CURR OPIN INFECT DIS, V16, P97, DOI 10.1097-01.aco.0000065077.06965.4D55

    Investigation of hallmark epigenetic changes in a cancer stem cell model

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    Epigenetic control of gene expression is vital for normal development and differentiation of cells, and is also important in the development of disease. In particular, there is a strong association between hallmark epigenetic changes and cancer – namely, genome wide hypomethylation, gene specific hypermethylation and characteristic histone modification. Almost all studies of cancer epigenetics to date have been conducted in malignant tissues or already transformed cell lines, and therefore do not take into account epigenetic changes occurring during the process of transformation. Our lab has developed a line of primary mesenchymal stem cells (MSC; thought to be the origin of various types of sarcoma) in which five oncogenic steps towards a fully transformed state are sequentially introduced including: human telomerase, necessary to extend the life span of MSC in culture, genes to inactivate the p53 and pRb tumour suppressor genes and genes to activate the oncogenes c-Myc and Ras. I hypothesized that hallmark epigenetic changes take place in this step-wise model of transformation, and aimed to investigate genome wide hypomethylation and the activity of the polycomb repressive 2 (PRC2) complex in this system. Utilizing the PCR based technique MethyLight, I show that transformed MSC are hypomethylated compared to parental MSC, with this decrease in methylation occurring on the introduction of oncogenic H-Ras in the final step. I also show that this hypomethylation is a gradual event following H-Ras expression, and transformation can take place in the absence of hypomethylation. I demonstrate that the three core components of the PRC2 complex are up-regulated during step-wise transformation and that PRC2 target genes are down-regulated. Finally, I show that MSC are able to be transformed when the PRC2 components EZH2 and SUZ12 are knocked down before the final oncogenic hit. These studies show that hallmark epigenetic changes occur during step-wise transformation and suggest that tumour-associated epigenetic changes occur following genetic aberrations. This model is valuable and relevant to further explore the mechanisms behind epigenetic alterations in cancer
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