Drosophila Neurotrophins Reveal a Common Mechanism for Nervous System Formation

Neurotrophic interactions occur in Drosophila, but to date, no neurotrophic factor had been found. Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate neuronal survival, targeting, synaptic plasticity, memory and cognition. We have identified a neurotrophic factor in flies, Drosophila Neurotrophin (DNT1), structurally related to all known neurotrophins and highly conserved in insects.By investigating with genetics the consequences of removing DNT1 or adding it in excess, we show that DNT1 maintains neuronal survival, as more neurons die in DNT1 mutants and expression of DNT1 rescues naturally occurring cell death, and it enables targeting by motor neurons. We show that Spa¨ tzle and a further fly neurotrophin superfamily member, DNT2, also have neurotrophic functions in flies. Our findings imply that most likely a neurotrophin was present in the common ancestor of all bilateral organisms, giving rise to invertebrate and vertebrate neurotrophins through gene or whole-genome duplications. This work provides a missing link between aspects of neuronal function in flies and vertebrates, and it opens the opportunity to use Drosophila to investigate further aspects of neurotrophin function and to model related diseases

Reliability and validity of the Infant and Toddler Quality of Life Questionnaire (ITQOL) in a general population and respiratory disease sample

Objective: To evaluate feasibility, internal consistency, test-retest reliability, and concurrent and discriminative validity of the Infant and Toddler Quality of Life Questionnaire (ITQOL) for parents of pre-school children with 12 scales (103-items) covering physical and psychosocial domains and impact of child health on parents, in comparison with the TNO-AZL Pre-school Children Quality of Life Questionnaire (TAPQOL). Methods: Parents of children from a random general population sample (2 months-4 years old; n = 500) and of an outpatient clinic sample of children with respiratory disease (5 months-51/2 years old; n = 217) were mailed ITQOL and TAPQOL questionnaires; a retest was sent after two weeks. Results: Feasibility: The response was ≥80% with few missing and non-unique ITQOL-answers (25% at maximum score). Internal consistency: All Cronbach's α >0.70. Test-retest Intraclass Correlation Coefficients (ICCs) were moderate or adequate (≥0.50; p < 0.01) for 10 ITQOL-scales. Validity: ITQOL-scales, with a few exceptions, correlated better with predefined parallel TAPQOL scales than with non-parallel scales. Five to eight ITQOL-scales discriminated clearly between children with few and with many parent-reported chronic conditions, between children with and without doctor-diagnosed respiratory disease and with a low and a high parent-reported medical consumption (p < 0.05). Conclusions: This study supported the evidence that the ITQOL is a feasible instrument with adequate psychometric properties. The study provided reference ITQOL scores for gender/age subgroups. We recommend repeated evaluations of the ITQOL in varied populations, especially among very young children, including repeated assessments of test-retest characteristics and evaluations of responsiveness to change. We recommend developing and evaluating a shortened ITQOL version

Psychological Functioning, Nonadherence and Health Outcomes After Pediatric Liver Transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74689/1/j.1600-6143.2007.01878.x.pd

Cognitive appraisal of environmental stimuli induces emotion-like states in fish

The occurrence of emotions in non-human animals has been the focus of debate over the years. Recently, an interest in expanding this debate to non-tetrapod vertebrates and to invertebrates has emerged. Within vertebrates, the study of emotion in teleosts is particularly interesting since they represent a divergent evolutionary radiation from that of tetrapods, and thus they provide an insight into the evolution of the biological mechanisms of emotion. We report that Sea Bream exposed to stimuli that vary according to valence (positive, negative) and salience (predictable, unpredictable) exhibit different behavioural, physiological and neuromolecular states. Since according to the dimensional theory of emotion valence and salience define a two-dimensional affective space, our data can be interpreted as evidence for the occurrence of distinctive affective states in fish corresponding to each the four quadrants of the core affective space. Moreover, the fact that the same stimuli presented in a predictable vs. unpredictable way elicited different behavioural, physiological and neuromolecular states, suggests that stimulus appraisal by the individual, rather than an intrinsic characteristic of the stimulus, has triggered the observed responses. Therefore, our data supports the occurrence of emotion-like states in fish that are regulated by the individual's perception of environmental stimuli.European Commission [265957 Copewell]; Fundacao para a Ciencia e Tecnologia [SFRH/BD/80029/2011, SFRH/BPD/72952/2010]info:eu-repo/semantics/publishedVersio

Quality of life in Type 1 (insulin-dependent) diabetic patients prior to and after pancreas and kidney transplantation in relation to organ function

Improvement of the quality of life in Type 1 (insulin-dependent) diabetic patients with severe late complications is one of the main goals of pancreas and/or kidney grafting. To assess the influences of these treatment modalities on the different aspects of the quality of life a cross-sectional study in 157 patients was conducted. They were categorized into patients pre-transplant without dialysis (n=29; Group A), pre-transplant under dialysis (n=44; Group B), post-transplant with pancreas and kidney functioning (n=31; Group C), post-transplant with functioning kidney, but insulin therapy (n=29; Group D), post-transplant under dialysis and insulin therapy again (n=15; Group E) and patients after single pancreas transplantation and rejection, with good renal function, but insulin therapy (n=9; Group F). All patients answered a mailed, self-administered questionnaire (217 questions) consisting of a broad spectrum of rehabilitation criteria. The results indicate a better quality of life in Groups C and D as compared to the other groups. In general the scores are highest in C, but without any significant difference to D. Impressive significant differences between C or D and the other groups were found especially in their satisfaction with physical capacity, leisure-time activities or the overall quality of life. The satisfaction with the latter is highest in C (mean±SEM: 4.0±0.2 on a 1 to 5-rating scale; significantly different from A: 3.1±0.1, B: 2.7±0.2 and E: 2.6±0.3; p<0.01), followed by D (3.8±0.2; significantly different from B and E; p<0.01). Group F shows a mean of 3.1±0.4, which is not significantly different from C. The percentages of patients in each group, who are not working: A: 38 %, B: 64 %, C: 74 %, D: 66 %, E: 87 % and F: 78 % indicate that there is no marked improvement in the vocational situation after successful grafting

Predictive models for fatigue property of laser powder bed fusion stainless steel 316L

The selection of appropriate processing parameters is crucial for producing parts with target properties via the laser powder bed fusion (L-PBF) process. In this work, the fatigue properties of L-PBF stainless steel 316L under controlled changes in laser power and scan speed were studied by employing the statistical response surface method. Processing regions corresponding to different fatigue failure mechanisms were identified. The optimum fatigue properties are associated with crack initiation from microstructure defect, which, by acting as the weakest link, creates enhanced porosity-tolerance at applied stress approaching the fatigue limit. Deviations from the optimum processing condition lead to strength degradation and porosity-driven cracking. Based on the observed relations between microstructural features and failure behaviour, a processing-independent fatigue prediction model was proposed. The microstructure-driven failure was modelled by a reference S-N curve where the intrinsic effect of microstructure inhomogeneity was accounted for by applying a reduction factor on fatigue life. For the porosity-driven failure, high cycle fatigue life follows an inverse-square-root relation with porosity fraction. This relation was incorporated into the Basquin equation for predicting the fatigue strength parameters.Accepted versio

Temporal and Spatial Regulation of miR-320 in the Uterus during Embryo Implantation in the Rat

The implantation process is complex, requiring reciprocal interactions between implantation-competent blastocysts and the receptive uterus. There were reports to show that some microRNAs (miRNAs) may play a key role during embryo implantation in mouse. However, the miR-320 expression profiles in the rat uterus during peri-implantation are unknown. In the present study, we found that the expression level of miR-320 was lower on day 5 of gestation (g.d. 5) in rats than g.d.3 and g.d.4 and restored gradually from g.d.6. MiR-320 was specifically localized in glandular and luminal epithelia and decidua. The expression of miR-320 was not significantly different in the pseudopregnant uterus and decreased in the uteri of rats subjected to activation of delayed implantation. Artificial decidualization and treatment with progesterone increased the miR-320 expression. Thus, miR-320 was differentially expressed in the rat uterus during implantation. The expression level was affected by active blastocysts and decidualization during the window of implantation. Steroid hormones, progesterone stimulated miR-320 expression

Human microRNA hsa-miR-125a-5p interferes with expression of hepatitis B virus surface antigen

MicroRNAs are small non-coding RNAs that modulate gene expression at post-transcriptional level, playing a crucial role in cell differentiation and development. Recently, some reports have shown that a limited number of mammalian microRNAs are also involved in anti-viral defense. In this study, the analysis of the hepatitis B virus (HBV) genome by the computer program MiRanda led to the identification of seven sites that are potential targets for human liver microRNAs. These sites were found to be clustered in a 995-bp segment within the viral polymerase ORF and the overlapping surface antigen ORF, and conserved among the most common HBV subtypes. The HBV genomic targets were then subjected to a validation test based on cultured hepatic cells (HepG2, HuH-7 and PLC/PRF/5) and luciferase reporter genes. In this test, one of the selected microRNAs, hsa-miR-125a-5p, was found to interact with the viral sequence and to suppress the reporter activity markedly. The microRNA was then shown to interfere with the viral translation, down-regulating the expression of the surface antigen. Overall, these results support the emerging concept that some mammalian microRNAs play a role in virus-host interaction. Furthermore, they provide the basis for the development of new strategies for anti-HBV intervention

Global impression of perceived difficulties in children and adolescents with attention-deficit/hyperactivity disorder: Reliability and validity of a new instrument assessing perceived difficulties from a patient, parent and physician perspective over the day

<p>Abstract</p> <p>Background</p> <p>The objective of this analysis was to evaluate the psychometric properties of a brief scale developed to assess the degree of difficulties in children with Attention-Deficit/Hyperactivity Disorder (ADHD). The Global Impression of Perceived Difficulties (GIPD) scale reflects overall impairment, psychosocial functioning and Quality of Life (QoL) as rated by patient, parents and physician at various times of the day.</p> <p>Methods</p> <p>In two open-label studies, ADHD-patients aged 6–17 years were treated with atomoxetine (target-dose 0.5–1.2 mg/kg/day). ADHD-related difficulties were assessed up to week 24 using the GIPD. Data from both studies were combined to validate the scale.</p> <p>Results</p> <p>Overall, 421 patients received atomoxetine. GIPD scores improved over time. All three GIPD-versions (patient, parent, physician) were internally consistent; all items showed at least moderate item-total correlation. The scale showed good test-retest reliability over a two-week period from all three perspectives. Good convergent and discriminant validity was shown.</p> <p>Conclusion</p> <p>GIPD is an internally consistent, reliable and valid measure to assess difficulties in children with ADHD at various times of the day and can be used as indicator for psychosocial impairment and QoL. The scale is sensitive to treatment-related change.</p

Does switching from oral extended-release methylphenidate to the methylphenidate transdermal system affect health-related quality-of-life and medication satisfaction for children with attention-deficit/hyperactivity disorder?

Background: To evaluate health-related quality of life (HRQL) and medication satisfaction after switching from a stable dose of oral extended-release methylphenidate (ER-MPH) to methylphenidate transdermal system (MTS) via a dose-transition schedule in children with attention-deficit/hyperactivity disorder (ADHD). Methods: In a 4-week, multisite, open-label study, 171 children (164 in the intent-to-treat [ITT] population) aged 6-12 years diagnosed with ADHD abruptly switched from a stable dose of oral ER-MPH to MTS nominal dosages of 10, 15, 20, and 30 mg using a predefined dose-transition schedule. Subjects remained on the scheduled dose for the first week, after which the dose was then titrated to an optimal effect. The ADHD Impact Module-Children (AIM-C), a disease-specific validated HRQL survey instrument measuring child and family impact, was used to assess the impact of ADHD symptoms on the lives of children and their families at baseline and study endpoint. Satisfaction with MTS use was assessed via a Medication Satisfaction Survey (MSS) at study endpoint. Both the AIM-C and MSS were completed by a caregiver (parent/legally authorized representative). Tolerability was monitored by spontaneous adverse event (AE) reporting. Results: AIM-C child and family HRQL mean scores were above the median possible score at baseline and were further improved at endpoint across all MTS doses. Similar improvements were noted for behavior, missed doses, worry, and economic impact AIM-C item scores. Overall, 93.8% of caregivers indicated a high level of satisfaction with their child's use of the study medication. The majority of treatment-emergent AEs (> 98%) were mild to moderate in intensity, and the most commonly reported AEs included headache, decreased appetite, insomnia, and abdominal pain. Seven subjects discontinued the study due to intolerable AEs (n = 3) and application site reactions (n = 4). Conclusion: This study demonstrates that MTS, when carefully titrated to optimal dose, may further improve child and family HRQL, as well as behavioral, medication worry, and economic impact item scores, as measured by the AIM-C in subjects switching to MTS from a stable dose of routinely prescribed oral ER-MPH after a short treatment period. Furthermore, following the abrupt conversion from oral ER-MPH to MTS, the majority of caregivers reported being highly satisfied with MTS as a treatment option for their children with ADHD. Trial Registration: NCT0015198