Phenotype of arylsulfatase A-deficient mice: Relationship to human metachromatic leukodystrophy

Metachromatic leukodystrophy is a lysosomal sphingolipid storage disorder caused by the deficiency of arylsulfatase A. The disease is characterized by progressive demyelination, causing various neurologic symptoms. Since no naturally occurring animal model of the disease is available, we have generated arylsulfatase A-deficient mice. Deficient animals store the sphingolipid cerebroside-3-sulfate in various neuronal and nonneuronal tissues. The storage pattern is comparable to that of affected humans, but gross defects of white matter were not observed up to the age of 2 years. A reduction of axonal cross-sectional area and an astrogliosis were observed in 1-year-old mice; activation of microglia started at 1 year and was generalized at 2 years. Purkinje cell dendrites show an altered morphology. In the acoustic ganglion numbers of neurons and myelinated fibers are severely decreased, which is accompanied by a loss of brainstem auditory-evoked potentials. Neurologic examination reveals significant impairment of neuromotor coordination.

Efeitos do treinamento de força no músculo esquelético em ratos com caquexia induzida pelo câncer

A ausência de terapias eficazes para a caquexia permanece como um problema central para o tratamento do câncer no mundo. Em contrapartida, o treinamento de força (i.e. também conhecido como treinamento resistido) tem sido amplamente utilizado como uma estratégia não farmacológica anticatabólica, prevenindo a perda da massa e da função da musculatura esquelética. Entretanto, o papel terapêutico do treinamento de força na caquexia do câncer permanece apenas especulativo. Portanto, nesse estudo avaliamos se o treinamento de força poderia atenuar a perda da massa e da função da musculatura esquelética em um severo modelo de caquexia do câncer em ratos. Para isso, ratos machos da linhagem Wistar foram randomizados em quatro grupos experimentais: 1) ratos sedentários injetados com solução salina na medula óssea (Controle); 2) ratos injetados com solução salina na medula óssea e submetidos ao treinamento de força (Controle + T); 3) ratos sedentários injetados com células do tumor Walker 256 na medula óssea (Tumor); e 4) ratos injetados com células do tumor Walker 256 na medula óssea e submetidos ao treinamento de força (Tumor + T). Foram avaliados a massa e a área de secção transversa da musculatura esquelética, marcadores de disfunção metabólica e do turnover proteico, a função da musculatura esquelética in vivo e ex vivo, o consumo alimentar, o crescimento tumoral e a sobrevida dos grupos experimentais com tumor. O grupo Tumor apresentou atrofia muscular após quinze dias da injeção das células tumorais como pode ser observado pela redução na massa dos músculos Plantaris (- 20,5%) e EDL (-20%). A atrofia no músculo EDL foi confirmada por análises histológicas, demonstrando uma redução de 43,8% na área de secção transversa. Embora o treinamento de força tenha aumentado o conteúdo proteico da lactato desidrogenase e revertido totalmente o conteúdo da forma fosforilada de 4EBP-1 (i.e. repressor da transcrição de mRNA), ele não atuou na morfologia da musculatura esquelética nos animais com tumor. Além disso, o treinamento de força não atenuou a perda de função da musculatura esquelética, a anorexia, o crescimento tumoral ou a taxa de mortalidade. Contudo, a força muscular, avaliada pelo teste de 1RM, apresentou uma correlação negativa com a sobrevida dos animais (p = 0,02), sugerindo que a perda de força prediz a mortalidade nesse modelo experimental de caquexia do câncer. Em suma, a injeção de células do tumor Walker 256 na medula óssea induz caquexia do câncer em ratos. O treinamento de força não foi eficaz em atenuar a perda de massa e função da musculatura esquelética nesse modelo. Entretanto, a força muscular prediz a sobrevida dos animais, sugerindo que novos estudos são necessários para elucidar o possível efeito terapêutico do treinamento de força para atenuar a caquexia do câncer e a progressão tumoral

Corneal Biomechanics, Retinal Nerve Fiber Layer, and Optic Disc in Children

Purpose: To evaluate the possible associations between corneal biomechanical parameters, optic disc morphology, and retinal nerve fiber layer (RNFL) thickness in healthy white Spanish children. Methods: This cross-sectional study included 100 myopic children and 99 emmetropic children as a control group, ranging in age from 6 to 17 years. The Ocular Response Analyzer was used to measure corneal hysteresis (CH) and corneal resistance factor. The optic disc morphology and RNFL thickness were assessed using posterior segment optical coherence tomography (Cirrus HD-OCT). The axial length was measured using an IOLMaster, whereas the central corneal thickness was measured by anterior segment optical coherence tomography (Visante OCT). Results: The mean (±SD) age and spherical equivalent were 12.11 (±2.76) years and −3.32 (±2.32) diopters for the myopic group and 11.88 (±2.97) years and +0.34 (±0.41) diopters for the emmetropic group. In a multivariable mixed-model analysis in myopic children, the average RNFL thickness and rim area correlated positively with CH (p = 0.007 and p = 0.001, respectively), whereas the average cup-to-disc area ratio correlated negatively with CH (p = 0.01). We did not observe correlation between RNFL thickness and axial length (p = 0.05). Corneal resistance factor was only positively correlated with the rim area (p = 0.001). The central corneal thickness did not correlate with the optic nerve parameters or with RNFL thickness. These associations were not found in the emmetropic group (p > 0.05 for all). Conclusions: The corneal biomechanics characterized with the Ocular Response Analyzer system are correlated with the optic disc profile and RNFL thickness in myopic children. Low CH values may indicate a reduction in the viscous dampening properties of the cornea and the sclera, especially in myopic children.

The impact of prolonged fasting during aestivation on the structure of the small intestine in the green-striped burrowing frog, Cyclorana alboguttata

The effects of short-term fasting and prolonged fasting during aestivation on the morphology of the proximal small intestine and associated organs were investigated in the green-striped burrowing frog, Cyclorana alboguttata (Anura: Hylidae). Animals were fasted for 1 week while active or for 3-9 months during aestivation. Short-duration fasting (1 week) had little effect on the morphology of the small intestine, whilst prolonged fasting during aestivation induced marked enteropathy including reductions in intestinal mass, length and diameter, longitudinal fold height and tunica muscularis thickness. Enterocyte morphology was also affected markedly by prolonged fasting: enterocyte cross-sectional area and microvillous height were reduced during aestivation, intercellular spaces were visibly reduced and the prevalence of lymphocytes amongst enterocytes was increased. Mitochondria and nuclei were also affected by 9 months of aestivation with major disruptions to mitochondrial cristae and increased clumping of nuclear material and increased infolding of the nuclear envelope. The present study demonstrates that the intestine of an aestivating frog responds to prolonged food deprivation during aestivation by reducing in size, presumably to reduce the energy expenditure of the organ.

Femtosecond laser-induced microstructures on diamond for microfluidic sensing devices applications

This paper reported a three-dimensional microfluidic channel structure, which was fabricated by Yb:YAG 1026?nm femtosecond laser irradiation on a single-crystalline diamond substrate. The femtosecond laser irradiation energy level was optimized at 100?kHz repetition rate with a sub-500 femtosecond pulse duration. The morphology and topography of the microfluidic channel were characterized by a scanning electron microscope and an atomic force microscope. Raman spectroscopy indicated that the irradiated area was covered by graphitic materials. By comparing the cross-sectional profiles before/after removing the graphitic materials, it could be deduced that the microfluidic channel has an average depth of ~410?nm with periodical ripples perpendicular to the irradiation direction. This work proves the feasibility of using ultra-fast laser inscription technology to fabricate microfluidic channels on biocompatible diamond substrates, which offers a great potential for biomedical sensing applications.

The impact of general intellectual ability and white matter volume on the functional outcome of patients with bipolar disorder and their relatives

Background: There is substantial evidence that cognitive deficits and brain structural abnormalities are present in patients with Bipolar Disorder (BD) and in their first-degree relatives. Previous studies have demonstrated associations between cognition and functional outcome in BD patients but have not examined the role of brain morphological changes. Similarly, the functional impact of either cognition or brain morphology in relatives remains unknown. Therefore we focused on delineating the relationship between psychosocial functioning, cognition and brain structure, in relation to disease expression and genetic risk for BD. Methods: Clinical, cognitive and brain structural measures were obtained from 41 euthymic BD patients and 50 of their unaffected first-degree relatives. Psychosocial function was evaluated using the General Assessment of Functioning (GAF) scale. We examined the relationship between level of functioning and general intellectual ability (IQ), memory, attention, executive functioning, symptomatology, illness course and total gray matter, white matter and cerebrospinal fluid volumes. Limitations: Cross-sectional design. Results: Multiple regression analyses revealed that IQ, total white matter volume and a predominantly depressive illness course were independently associated with functional outcome in BD patients, but not in their relatives, and accounted for a substantial proportion (53%) of the variance in patients' GAF scores. There were no significant domain-specific associations between cognition and outcome after consideration of IQ. Conclusions: Our results emphasise the role of IQ and white matter integrity in relation to outcome in BD and carry significant implications for treatment interventions. © 2010 Elsevier B.V.

Femtosecond laser-induced microstructures on diamond for microfluidic sensing device applications

This paper reported a three-dimensional microfluidic channel structure, which was fabricated by Yb:YAG 1026?nm femtosecond laser irradiation on a single-crystalline diamond substrate. The femtosecond laser irradiation energy level was optimized at 100?kHz repetition rate with a sub-500 femtosecond pulse duration. The morphology and topography of the microfluidic channel were characterized by a scanning electron microscope and an atomic force microscope. Raman spectroscopy indicated that the irradiated area was covered by graphitic materials. By comparing the cross-sectional profiles before/after removing the graphitic materials, it could be deduced that the microfluidic channel has an average depth of ~410?nm with periodical ripples perpendicular to the irradiation direction. This work proves the feasibility of using ultra-fast laser inscription technology to fabricate microfluidic channels on biocompatible diamond substrates, which offers a great potential for biomedical sensing applications.

Femtosecond laser-induced microstructures on diamond for microfluidic sensing devices applications

This paper reported a three-dimensional microfluidic channel structure, which was fabricated by Yb:YAG 1026?nm femtosecond laser irradiation on a single-crystalline diamond substrate. The femtosecond laser irradiation energy level was optimized at 100?kHz repetition rate with a sub-500 femtosecond pulse duration. The morphology and topography of the microfluidic channel were characterized by a scanning electron microscope and an atomic force microscope. Raman spectroscopy indicated that the irradiated area was covered by graphitic materials. By comparing the cross-sectional profiles before/after removing the graphitic materials, it could be deduced that the microfluidic channel has an average depth of ~410?nm with periodical ripples perpendicular to the irradiation direction. This work proves the feasibility of using ultra-fast laser inscription technology to fabricate microfluidic channels on biocompatible diamond substrates, which offers a great potential for biomedical sensing applications.

Optical and structural ocular changes during incipient presbyopia

The primary aim of this thesis was to investigate the in vivo ocular morphological and contractile changes occurring within the accommodative apparatus prior to the onset of presbyopia, with particular reference to ciliary muscle changes with age and the origin of a myopic shift in refraction during incipient presbyopia. Commissioned semi-automated software proved capable of extracting accurate and repeatable measurements from crystalline lens and ciliary muscle Anterior Segment Optical Coherence Tomography (AS-OCT) images and reduced the subjectivity of AS-OCT image analysis. AS-OCT was utilised to document longitudinal changes in ciliary muscle morphology within an incipient presbyopic population (n=51). A significant antero-inwards shift of ciliary muscle mass was observed after 2.5 years. Furthermore, in a subgroup study (n=20), an accommodative antero-inwards movement of ciliary muscle mass was evident. After 2.5 years, the centripetal response of the ciliary muscle significantly attenuated during accommodation, whereas the antero-posterior mobility of the ciliary muscle remained invariant. Additionally, longitudinal measurement of ocular biometry revealed a significant increase in crystalline lens thickness and a corresponding decrease in anterior chamber depth after 2.5 years (n=51). Lenticular changes appear to be determinant of changes in refraction during incipient presbyopia. During accommodation, a significant increase in crystalline lens thickness and axial length was observed, whereas anterior chamber depth decreased (n=20). The change in ocular biometry per dioptre of accommodation exerted remained invariant after 2.5 years. Cross-sectional ocular biometric data were collected to quantify accommodative axial length changes from early adulthood to advanced presbyopia (n=72). Accommodative axial length elongation significantly attenuated during presbyopia, which was consistent with a significant increase in ocular rigidity during presbyopia. The studies presented in this thesis support the Helmholtz theory of accommodation and despite the reduction in centripetal ciliary muscle contractile response with age, primarily implicate lenticular changes in the development of presbyopia.

Antecedents and consequences of percieved effective managerial coaching:an individual, team-level and cross-level examination

The major contribution of the study is the identification of a positive link between perceived effective managerial coaching (PEMC) and team task performance and also, the examination of PEMC adopting a multilevel research design and incorporating dual-source data. Specifically, drawing on social psychology, the thesis aims at developing and testing a comprehensive conceptual framework of the antecedents and consequences of PEMC for knowledge workers. The model takes into consideration intrapersonal, interpersonal and team-level characteristics, which relate to PEMC and, subsequently associate with important work outcomes. In this regard, the thesis identifies PEMC as a practice of dual nature in that it may be experienced not only as a one-on-one workplace developmental interaction, but also as a managerial practice that is experienced by each member of a team for co-ordination purposes. Adopting a cross-sectional survey research design, the hypotheses are tested in three organisations in Greece and the UK. In particular, hierarchical linear modelling of 191 employees nested in 60 teams yields that employees’ learning goal orientation (LGO) and high-quality exchanges between an employee and a manager (LMX) are positively related to effective MC, while a manager’s LGO moderates the relationship between employees’ LGO and PEMC. In turn, PEMC, as a one-on-one practice, is related to cognitive outcomes, such as information sharing, while as a shared team practice is related also to behavioural outcomes, including individual and team performance. Overall, the study contributes to a growing body of coaching and management literature that acknowledges PEMC as a core managerial practice.

Cross-section and panel estimates of peer effects in early adolescent cannabis use: With a little help from my ‘friends once removed’

Peer effects in adolescent cannabis are difficult to estimate, due in part to the lack of appropriate data on behaviour and social ties. This paper exploits survey data that have many desirable properties and have not previously been used for this purpose. The data set, collected from teenagers in three annual waves from 2002-2004 contains longitudinal information about friendship networks within schools (N = 5,020). We exploit these data on network structure to estimate peer effects on adolescents from their nominated friends within school using two alternative approaches to identification. First, we present a cross-sectional instrumental variable (IV) estimate of peer effects that exploits network structure at the second degree, i.e. using information on friends of friends who are not themselves ego’s friends to instrument for the cannabis use of friends. Second, we present an individual fixed effects estimate of peer effects using the full longitudinal structure of the data. Both innovations allow a greater degree of control for correlated effects than is commonly the case in the substance-use peer effects literature, improving our chances of obtaining estimates of peer effects than can be plausibly interpreted as causal. Both estimates suggest positive peer effects of non-trivial magnitude, although the IV estimate is imprecise. Furthermore, when we specify identical models with behaviour and characteristics of randomly selected school peers in place of friends’, we find effectively zero effect from these ‘placebo’ peers, lending credence to our main estimates. We conclude that cross-sectional data can be used to estimate plausible positive peer effects on cannabis use where network structure information is available and appropriately exploited.

Knowledge about sources of dietary fibres and health effects using a validated scale: a cross-country study

Objectives Dietary fibre (DF) is one of the components of diet that strongly contributes to health improvements, particularly on the gastrointestinal system. Hence, this work intended to evaluate the relations between some sociodemographic variables such as age, gender, level of education, living environment or country on the levels of knowledge about dietary fibre (KADF), its sources and its effects on human health, using a validated scale. Study design The present study was a cross-sectional study. Methods A methodological study was conducted with 6010 participants, residing in 10 countries from different continents (Europe, America, Africa). The instrument was a questionnaire of self-response, aimed at collecting information on knowledge about food fibres. The instrument was used to validate a scale (KADF) which model was used in the present work to identify the best predictors of knowledge. The statistical tools used were as follows: basic descriptive statistics, decision trees, inferential analysis (t-test for independent samples with Levene test and one-way ANOVA with multiple comparisons post hoc tests). Results The results showed that the best predictor for the three types of knowledge evaluated (about DF, about its sources and about its effects on human health) was always the country, meaning that the social, cultural and/or political conditions greatly determine the level of knowledge. On the other hand, the tests also showed that statistically significant differences were encountered regarding the three types of knowledge for all sociodemographic variables evaluated: age, gender, level of education, living environment and country. Conclusions The results showed that to improve the level of knowledge the actions planned should not be delineated in general as to reach all sectors of the populations, and that in addressing different people, different methodologies must be designed so as to provide an effective health education.

Sources of Information about Dietary Fibre: A Cross-Country Survey

Problem statement: Dietary fibre (DF) has been recognized as a major determinant for improvement of health. Hence the means of information through which people become aware of its benefits are crucial. Research questions: Where do you usually find information about dietary fibre? What means of communication do you consider the most appropriate to encourage the consumption of dietary fibre? Purpose of the study: This work aimed at studying the sources of information about dietary fibre, as a means to educate people about aspects related to healthy eating. Factors such as gender, level of education, living environment or country were evaluated as to their effect on the selection of sources and preferences.   Research Methods: Descriptive cross-sectional study by means of a questionnaire, applied to a non-probabilistic sample of 6010 participants from 10 countries in different continents (Europe, Africa and America), answered after informed consent by all participants. For the analysis were used several descriptive statistics tools, crosstabs and chi square test to assess the relations between some of the variables under study. Findings: Mostly the information about DF comes from the internet, but television is recognized as suitable. Differences were found between genders, levels of education, living environments and countries. The internet (preferred source), got highest scores for Hungary, urban areas, university education and female gender. The radio (least scored source) was preferred in Egypt, for men and with lower education (primary school). Conclusions: People get information through the internet due to easy access. However, it is to some extent a risk given the impossibility to control de information made public on the internet. The role of health centres and hospitals as well as schools should definitely be increased, as a responsible way to ensure correct information.

Sources of Information about Dietary Fibre: A Cross-Country Survey

Dietary fibre (DF) has been recognized as a major determinant for improvement of health. Hence the means of information through which people become aware of its benefits are crucial. This work aimed at studying the sources of information about DF, as a means to educate people about aspects related to healthy eating. Factors such as gender, level of education, living environment or country were evaluated as to their effect on the selection of sources and preferences. For this, a descriptive cross-sectional study by means of a questionnaire, applied to a non-probabilistic sample of 6010 participants from 10 countries in different continents (Europe, Africa and America), answered after informed consent by all participants. For the analysis were used several descriptive statistics tools, crosstabs and chi square test to assess the relations between some of the variables under study. The results showed that mostly the information about DF comes from the internet, but the participants recognize that television might be a most suitable way to disseminate information about DF. The results also indicated differences between genders, levels of education, living environments and countries. The internet, the preferred source of information, got highest scores for Hungary, for urban areas, for university level of education and for female gender. The radio, the least scored source of information, was preferred in Egypt, for men and with lower education (primary school). As a conclusion, people get information through the internet due to easy access. However, it is to some extent a risk given the impossibility to control de information made public on the internet. The role of health centers and hospitals as well as schools should definitely be increased, as a responsible way to ensure correct information.