Ellis-van Creveld Syndrome in Grey Alpine Cattle: Morphologic, Immunophenotypic, and Molecular Characterization

Ellis-van Creveld (EvC) syndrome is a human autosomal recessive disorder caused by a mutation in either the EVC or EVC2 gene, and presents with short limbs, polydactyly, and ectodermal and heart defects. The aim of this study was to understand the pathologic basis by which deletions in the EVC2 gene lead to chondrodysplastic dwarfism and to describe the morphologic, immunohistochemical, and molecular hallmarks of EvC syndrome in cattle. Five Grey Alpine calves, with a known mutation in the EVC2 gene, were autopsied. Immunohistochemistry was performed on bone using antibodies to collagen II, collagen X, sonic hedgehog, fibroblast growth factor 2, and Ki67. Reverse transcription polymerase chain reaction was performed to analyze EVC1 and EVC2 gene expression. Autopsy revealed long bones that were severely reduced in length, as well as genital and heart defects. Collagen II was detected in control calves in the resting, proliferative, and hypertrophic zones and in the primary and secondary spongiosa, with a loss of labeling in the resting zone of 2 dwarfs. Collagen X was expressed in hypertrophic zone in the controls but was absent in the EvC cases. In affected calves and controls, sonic hedgehog labeled hypertrophic chondrocytes and primary and secondary spongiosa similarly. FGF2 was expressed in chondrocytes of all growth plate zones in the control calves but was lost in most EvC cases. The Ki67 index was lower in cases compared with controls. EVC and EVC2 transcripts were detected. Our data suggest that EvC syndrome of Grey Alpine cattle is a disorder of chondrocyte differentiation, with accelerated differentiation and premature hypertrophy of chondrocytes, and could be a spontaneous model for the equivalent human disease.

Structural brain correlates of defective gesture performance in schizophrenia

INTRODUCTION The neural correlates of impaired performance of gestures are currently unclear. Lesion studies showed variable involvement of the ventro-dorsal stream particularly left inferior frontal gyrus (IFG) in gesture performance on command. However, findings cannot be easily generalized as lesions may be biased by the architecture of vascular supply and involve brain areas beyond the critical region. The neuropsychiatric syndrome of schizophrenia shares apraxic-like errors and altered brain structure without macroanatomic lesions. Schizophrenia may therefore qualify as a model disorder to test neural correlates of gesture impairments. METHODS We included 45 schizophrenia patients and 44 healthy controls in the study to investigate the structural brain correlates of defective gesturing in schizophrenia using voxel based morphometry. Gestures were tested in two domains: meaningful gestures (transitive and intransitive) on verbal command and imitation of meaningless gestures. Cut-off scores were used to separate patients with deficits, patients without deficits and controls. Group differences in gray matter (GM) volume were explored in an ANCOVA. RESULTS Patients performed poorer than controls in each gesture category (p < .001). Patients with deficits in producing meaningful gestures on command had reduced GM predominantly in left IFG, with additional involvement of right insula and anterior cingulate cortex. Patients with deficits differed from patients without deficits in right insula, inferior parietal lobe (IPL) and superior temporal gyrus. CONCLUSIONS Impaired performance of meaningful gestures on command was linked to volume loss predominantly in the praxis network in schizophrenia. Thus, the behavioral similarities between apraxia and schizophrenia are paralleled by structural alterations. However, few associations between behavioral impairment and structural brain alterations appear specific to schizophrenia.

RB-mediated suppression of spontaneous multiple neuroendocrine neoplasia and lung metastases in Rb+/− mice

Alterations in pathways mediated by retinoblastoma susceptibility gene (RB) product are among the most common in human cancer. Mice with a single copy of the Rb gene are shown to develop a syndrome of multiple neuroendocrine neoplasia. The earliest Rb-deficient atypical cells were identified in the intermediate and anterior lobes of the pituitary, the thyroid and parathyroid glands, and the adrenal medulla within the first 3 months of postnatal development. These cells form gross tumors with various degrees of malignancy by postnatal day 350. By age of 380 days, 84% of Rb+/− mice exhibited lung metastases from C-cell thyroid carcinomas. Expression of a human RB transgene in the Rb+/− mice suppressed carcinogenesis in all tissues studied. Of particular clinical relevance, the frequency of lung metastases also was reduced to 12% in Rb+/− mice by repeated i.v. administration of lipid-entrapped, polycation-condensed RB complementary DNA. Thus, in spite of long latency periods during which secondary alterations can accumulate, the initial loss of Rb function remains essential for tumor progression in multiple types of neuroendocrine cells. Restoration of RB function in humans may prove an effective general approach to the treatment of RB-deficient disseminated tumors.

Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly

At least 11 complementation groups (CGs) have been identified for the peroxisome biogenesis disorders (PBDs) such as Zellweger syndrome, for which seven pathogenic genes have been elucidated. We have isolated a human PEX19 cDNA (HsPEX19) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary cell line, ZP119, defective in import of both matrix and membrane proteins. This cDNA encodes a hydrophilic protein (Pex19p) comprising 299 amino acids, with a prenylation motif, CAAX box, at the C terminus. Farnesylated Pex19p is partly, if not all, anchored in the peroxisomal membrane, exposing its N-terminal part to the cytosol. A stable transformant of ZP119 with HsPEX19 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX19 expression also restored peroxisomal protein import in fibroblasts from a patient (PBDJ-01) with Zellweger syndrome of CG-J. This patient (PBDJ-01) possessed a homozygous, inactivating mutation: a 1-base insertion, A764, in a codon for Met255, resulted in a frameshift, inducing a 24-aa sequence entirely distinct from normal Pex19p. These results demonstrate that PEX19 is the causative gene for CG-J PBD and suggest that the C-terminal part, including the CAAX homology box, is required for the biological function of Pex19p. Moreover, Pex19p is apparently involved at the initial stage in peroxisome membrane assembly, before the import of matrix protein.

ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response

The ATM gene is mutated in the syndrome of ataxia telangiectasia (AT), associated with neurologic dysfunction, growth abnormalities, and extreme radiosensitivity. Insulin-like growth factor-I receptor (IGF-IR) is a cell surface receptor with tyrosine kinase activity that can mediate mitogenesis, cell transformation, and inhibition of apoptosis. We report here that AT cells express low levels of IGF-IR and show decreased IGF-IR promoter activity compared with wild-type cells. Complementation of AT cells with the ATM cDNA results in increased IGF-IR promoter activity and elevated IGF-IR levels, whereas expression in wild-type cells of a dominant negative fragment of ATM specifically reduces IGF-IR expression, results consistent with a role for ATM in regulating IGF-IR expression at the level of transcription. When expression of IGF-IR cDNA is forced in AT cells via a heterologous viral promoter, near normal radioresistance is conferred on the cells. Conversely, in ATM cells complemented with the ATM cDNA, specific inhibition of the IGF-IR pathway prevents correction of the radiosensitivity. Taken together, these results establish a fundamental link between ATM function and IGF-IR expression and suggest that reduced expression of IGF-IR contributes to the radiosensitivity of AT cells. In addition, because IGF-I plays a major role in human growth and metabolism and serves as a survival and differentiation factor for developing neuronal tissue, these results may provide a basis for understanding other aspects of the AT syndrome, including the growth abnormalities, insulin resistance, and neurodegeneration.

Agouti regulation of intracellular calcium: role in the insulin resistance of viable yellow mice.

Several dominant mutations at the agouti locus in the mouse cause a syndrome of marked obesity, hyperinsulinemia, and insulin resistance. Although it is known that the agouti gene is expressed in an ectopic manner in these mutants, the precise mechanism by which the agouti gene product mediates these effects is unclear. Since intracellular Ca2+ is believed to play a role in mediating insulin action and dysregulation of Ca2+ flux is observed in diabetic animals and humans, we examined the status of intracellular Ca2+ in mice carrying the dominant agouti allele, viable yellow (Avy). We show here that in mice carrying this mutation, the intracellular free calcium concentration ([Ca2+]i) is elevated in skeletal muscle, and the degree of elevation is closely correlated with the degree to which the mutant traits are expressed in individual animals. Moreover, we demonstrate that the agouti gene product is capable of inducing increased [Ca2+]i in cultured and freshly isolated skeletal muscle myocytes from wild-type mice. Based on these findings, we present a model in which we propose that the agouti polypeptide promotes insulin resistance in mutant animals through its ability to increase [Ca2+]i.

La prevalencia del estrés laboral asistencial entre los profesores universitarios

El burnout, o estrés laboral asistencial, es un síndrome psicológico caracterizado por agotamiento emocional (CE), despersonalización (DP) e insatisfacción personal con los logros (RP). Se conoce poco acerca de la presencia de este síndrome en muestras representativas de profesores universitarios. Los objetivos del estudio son (a) conocer la prevalencia del burnout en un contexto universitario, (b) examinar la presencia del burnout en relación con la edad, género y categoría académica en un estudio transversal mediante cuestionario anónimo enviado por correo, y (e) explorar la relación entre el burnout y diversas variables de calidad de vida, satisfacción laboral y salud. Respondieron el cuestionario un total de 331 profesores en el contexto de un programa de calidad de vida de la Universidad de Alicante (España), lo que supone una tasa de respuesta del 56,2%. Se remitieron por correo a todos los profesores, seleccionados al azar del conjunto de todos los centros, un ejemplar del cuestionario junto con las instrucciones y sobre de devolución. El estrés laboral asistencial se midió a través del Maslach Burnout lnventory (MBI) estableciéndose una situación definida por altas puntuaciones en CE y DE, y bajas en RP. Este instrumento presenta un total de 22 ítems con siete alternativas de respuesta, desde 0 (nunca experimento este sentimiento) hasta 6 (todos los días experimento este sentimiento). Nuestros resultados muestran que un reducido porcentaje de profesores, el 1,8%, experimentan el síndrome de burnout. Cuando se analizan por separado las tres dimensiones que componen el burnout se observa que un 17,8% de los profesores se siente emocionalmente exhausto en su trabajo (puntuación e» 25), un 4,2% ha desarrollado una actitud negativa hacia los estudiantes puntuación e» 10), y un 42% se siente un escasa autorrealización personal en el trabajo (puntuación d»32). CE presenta unas correlaciones medias moderadas con las variables de salud (r= 0.42) y con calidad de vida (r=0.33). Un patrón relacional menos consistente se da en las restantes dimensiones del burnout. La edad, el género y la categoría académica de los profesores no se relacionan con los niveles de burnout. Se concluye que el burnout es un síndrome poco común en profesores universitarios.

Animal migration: is there a common migratory syndrome?

Ornithologists, and especially northern hemisphere ornithologists, have traditionally thought of migration as an annual return movement of populations between regular breeding and non-breeding grounds. Problems arise because selection does not ordinarily act on populations and because organisms of many taxa (including birds) are clearly migrants, but fail to undertake movements of the kind described. There are also extensive return movements that are not migratory. I propose that it is more useful to think of migration as a syndrome of behavioral and other traits that function together within individuals, and that such a syndrome provides a common ground across taxa from aphids to albatrosses. Large-scale return movements of populations are one outcome of the syndrome. Similar behavioral and physiological traits serve both to define migration and to provide a test for it. I use two insect (Hemipteran) examples to illustrate migratory syndromes and to demonstrate that, in many migrants, behavior and physiology correlate with life history and morphological traits to form syndromes at two levels. I then compare the two Hemipterans with migration in birds, butterflies, and fish to assess the question of whether there are migratory syndromes in common between these diverse migrants. Syndromes are more similar at the level of behavior than when morphology and life history traits are included. Recognizing syndromes leads to important evolutionary questions concerning migration strategies, trade-offs, the maintenance of genetic variance and the responses of migratory syndromes to both similar and different selective regimes.

The relationship between job structure, burnout, and coping methods among public school county bus drivers, bus aides, mechanics, and clerical workers

The purpose of this study was to examine the relationship between the structure of jobs and burnout, and to assess to what extent, if any this relationship was moderated by individual coping methods. This study was supported by the Karasek's (1998) Job Demand-Control-Support theory of work stress as well as Maslach and Leiter's (1993) theory of burnout. Coping was examined as a moderator based on the conceptualization of Lazarus and Folkman (1984). ^ Two overall overarching questions framed this study: (a) what is the relationship between job structure, as operationalized by job title, and burnout across different occupations in support services in a large municipal school district? and (b) To what extent do individual differences in coping methods moderate this relationship? ^ This study was a cross-sectional study of county public school bus drivers, bus aides, mechanics, and clerical workers (N = 253) at three bus depot locations within the same district using validated survey instruments for data collection. Hypotheses were tested using simultaneous regression analyses. ^ Findings indicated that there were statistically significant and relevant relationships among the variables of interest; job demands, job control, burnout, and ways of coping. There was a relationship between job title and physical job demands. There was no evidence to support a relationship between job title and psychological demands. Furthermore, there was a relationship between physical demands, emotional exhaustion and personal accomplishment; key indicators of burnout. ^ Results showed significant correlations between individual ways of coping as a moderator between job structure, operationalized by job title, and individual employee burnout adding empirical evidence to the occupational stress literature. Based on the findings, there are implications for theory, research, and practice. For theory and research, the findings suggest the importance of incorporating transactional models in the study of occupational stress. In the area of practice, the findings highlight the importance of enriching jobs, increasing job control, and providing individual-level training related to stress reduction.^

THE EFFECT OF PREECLAMPSIA ON RENAL FUNCTION: CROSS-SECTIONAL STUDIES OF POSTPARTUM PREECLAMPTICS AND WOMEN WHO WERE DESTINED TO DEVELOP PREECLAMPSIA

Preeclampsia (PE) is a pregnancy complication that is new-onset of hypertension and proteinuria after 20 weeks of gestation. However, subclinical renal dysfunction may be apparent earlier in gestation prior to the clinical presentation of PE. Although the maternal syndrome of PE resolves early postpartum, women with a history of PE are at higher risk of renal dysfunction later in life. Mineral metabolism, such as phosphate balance is heavily dependent on renal function, yet, phosphate handling in women with a history of PE is largely unknown. To investigate whether women with a history of PE would exhibit changes in phosphate metabolism compared to healthy parous women, phosphate loading test was used. Women with or without a history of PE, who were 6 months to 5 years postpartum, were recruited for this study. Blood and urine samples were collected before and after the oral dosing of 500mg phosphate solution. Biochemical markers of phosphate metabolism and renal function were evaluated. In order to assess the difference in renal function alteration between first trimester women who were or were not destined to develop PE, plasma cystatin C concentration was analysed. After phosphate loading, women with a history of PE had significantly elevated serum phosphate at both 1- and 2-hour, while controls had higher urine phosphate:urine creatinine excretion ratio at 1-hour than women with a history of PE. Women with a history of PE had no changes in intact parathyroid hormone (iPTH) concentration throughout the study period, whereas controls had elevated iPTH at 1-hour from baseline. In terms of renal function in the first trimester, there was no difference in plasma cystatin C concentration between women who were or were not destined to develop PE. The elevation of serum phosphate in women with a history of PE could be due to the delay in phosphate excretion. Prolong elevation of serum phosphate can have serious consequences later in life. Thus, oral phosphate challenge may serve as a useful method of early screening for altered phosphate metabolism and renal function.

THE EFFECT OF PREECLAMPSIA ON RENAL FUNCTION: CROSS-SECTIONAL STUDIES OF POSTPARTUM PREECLAMPTICS AND WOMEN WHO WERE DESTINED TO DEVELOP PREECLAMPSIA

Preeclampsia (PE) is a pregnancy complication that is new-onset of hypertension and proteinuria after 20 weeks of gestation. However, subclinical renal dysfunction may be apparent earlier in gestation prior to the clinical presentation of PE. Although the maternal syndrome of PE resolves early postpartum, women with a history of PE are at higher risk of renal dysfunction later in life. Mineral metabolism, such as phosphate balance is heavily dependent on renal function, yet, phosphate handling in women with a history of PE is largely unknown. To investigate whether women with a history of PE would exhibit changes in phosphate metabolism compared to healthy parous women, phosphate loading test was used. Women with or without a history of PE, who were 6 months to 5 years postpartum, were recruited for this study. Blood and urine samples were collected before and after the oral dosing of 500mg phosphate solution. Biochemical markers of phosphate metabolism and renal function were evaluated. In order to assess the difference in renal function alteration between first trimester women who were or were not destined to develop PE, plasma cystatin C concentration was analysed. After phosphate loading, women with a history of PE had significantly elevated serum phosphate at both 1- and 2-hour, while controls had higher urine phosphate:urine creatinine excretion ratio at 1-hour than women with a history of PE. Women with a history of PE had no changes in intact parathyroid hormone (iPTH) concentration throughout the study period, whereas controls had elevated iPTH at 1-hour from baseline. In terms of renal function in the first trimester, there was no difference in plasma cystatin C concentration between women who were or were not destined to develop PE. The elevation of serum phosphate in women with a history of PE could be due to the delay in phosphate excretion. Prolong elevation of serum phosphate can have serious consequences later in life. Thus, oral phosphate challenge may serve as a useful method of early screening for altered phosphate metabolism and renal function.

Burnout nos docentes de enfermagem

Dissertação de mest. em Ciências da Educação na Especialidade de Observação e Análise da Relação Educativa, Faculdade de Ciências Humanas e Sociais, Universidade do Algarve, 2003

The Relationship between Job Structure, Burnout, and Coping Methods among Public School county Bus Drivers, Bus Aides, Mechanics, and Clerical Workers

The purpose of this study was to examine the relationship between the structure of jobs and burnout, and to assess to what extent, if any this relationship was moderated by individual coping methods. This study was supported by the Karasek's (1998) Job Demand-Control-Support theory of work stress as well as Maslach and Leiter's (1993) theory of burnout. Coping was examined as a moderator based on the conceptualization of Lazarus and Folkman (1984). Two overall overarching questions framed this study: (a) what is the relationship between job structure, as operationalized by job title, and burnout across different occupations in support services in a large municipal school district? and (b) To what extent do individual differences in coping methods moderate this relationship? This study was a cross-sectional study of county public school bus drivers, bus aides, mechanics, and clerical workers (N = 253) at three bus depot locations within the same district using validated survey instruments for data collection. Hypotheses were tested using simultaneous regression analyses. Findings indicated that there were statistically significant and relevant relationships among the variables of interest; job demands, job control, burnout, and ways of coping. There was a relationship between job title and physical job demands. There was no evidence to support a relationship between job title and psychological demands. Furthermore, there was a relationship between physical demands, emotional exhaustion and personal accomplishment; key indicators of burnout. Results showed significant correlations between individual ways of coping as a moderator between job structure, operationalized by job title, and individual employee burnout adding empirical evidence to the occupational stress literature. Based on the findings, there are implications for theory, research, and practice. For theory and research, the findings suggest the importance of incorporating transactional models in the study of occupational stress. In the area of practice, the findings highlight the importance of enriching jobs, increasing job control, and providing individual-level training related to stress reduction.

Estou em Burnout

Dissertação de Mestrado apresentada no ISPA - Instituto Superior

Prevalência de sintomatologia músculo-esquelética e Burnout em Fisioterapeutas

Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Licenciada em Fisioterapia