CFU-S(11) activity does not localize solely with the aorta in the aorta-gonad-mesonephros region

The aorta-gonad-mesonephros (AGM) region is a potent hematopoietic site in the midgestation mouse conceptus and first contains colony-forming units-spleen day 11 (CFU-S(11)) at embryonic day 10 (E10). Because CFU-S(11) activity is present in the AGM region before the onset of hematopoietic stem cell (HSC) activity, CFU-S(11) activity in the complex developing vascular and urogenital regions of the AGM was localized. From E10 onward, CFU-S(11) activity is associated with the aortic vasculature, and is found also in the urogenital ridges (UGRs). Together with data obtained from organ explant cultures, in which up to a 16-fold increase in CFU-S(11) activity was observed, it was determined that CFU-S(11) can be increased autonomously both in vascular sites and in UGRs. Furthermore, CFU-S(11) activity is present in vitelline and umbilical vessels. This, together with the presence of CFU-S(11) in the UGRs 2 days before HSC activity, suggests both temporally and spatially distinct emergent sources of CFU-S(11). (Blood. 2000;96:2902-2904

Changes in Natural Killer Cell Activation and Function during Primary HIV-1 Infection

Background: Recent reports suggest that Natural Killer (NK) cells may modulate pathogenesis of primary HIV-1 infection. However, HIV dysregulates NK-cell responses. We dissected this bi-directional relationship to understand how HIV impacts NK-cell responses during primary HIV-1 infection. Methodology/Principal Findings: Paired samples from 41 high-risk, initially HIV-uninfected CAPRISA004 participants were analysed prior to HIV acquisition, and during viraemic primary HIV-1 infection. At the time of sampling post-infection five women were seronegative, 11 women were serodiscordant, and 25 women were seropositive by HIV-1 rapid immunoassay. Flow cytometry was used to measure NK and T-cell activation, NK-cell receptor expression, cytotoxic and cytokine-secretory functions, and trafficking marker expression (CCR7, α$_4$β$_7$). Non-parametric statistical tests were used. Both NK cells and T-cells were significantly activated following HIV acquisition (p = 0.03 and p<0.0001, respectively), but correlation between NK-cell and T-cell activation was uncoupled following infection (pre-infection r = 0.68;p<0.0001; post-infection, during primary infection r = 0.074;p = 0.09). Nonetheless, during primary infection NK-cell and T-cell activation correlated with HIV viral load (r = 0.32'p = 0.04 and r = 0.35;p = 0.02, respectively). The frequency of Killer Immunoglobulin-like Receptor-expressing (KIR$_{pos}$) NK cells increased following HIV acquisition (p = 0.006), and KIR$_{pos}$ NK cells were less activated than KIR$_{neg}$ NK cells amongst individuals sampled while seronegative or serodiscordant (p = 0.001;p<0.0001 respectively). During HIV-1 infection, cytotoxic NK cell responses evaluated after IL-2 stimulation alone, or after co-culture with 721 cells, were impaired (p = 0.006 and p = 0.002, respectively). However, NK-cell IFN-y secretory function was not significantly altered. The frequency of CCR7+ NK cells was elevated during primary infection, particularly at early time-points (p<0.0001). Conclusions/Significance: Analyses of immune cells before and after HIV infection revealed an increase in both NK-cell activation and KIR expression, but reduced cytotoxicity during acute infection. The increase in frequency of NK cells able to traffic to lymph nodes following HIV infection suggests that these cells may play a role in events in secondary lymphoid tissue

Motives for choosing growth-enhancing hormone treatment in adolescents with idiopathic short stature: a questionnaire and structured interview study

Background Growth-enhancing hormone treatment is considered a possible intervention in short but otherwise healthy adolescents. Although height gain is an obvious measure for evaluating hormone treatment, this may not be the ultimate goal for the person, but rather a means to reach other goals such as the amelioration of current height-related psychosocial problems or the enhancement of future prospects in life and society. The aim of our study was to clarify the motives of adolescents and their parents when choosing to participate in a growth-enhancing trial combining growth hormone and puberty-delaying hormone treatment. Methods Participants were early pubertal adolescents (25 girls, 13 boys) aged from 11 to 13 years (mean age 11.5 years) with a height standard deviation score (SDS) ranging from -1.03 to -3.43. All had been classified as idiopathic short stature or persistent short stature born small for the gestational age (intrauterine growth retardation) on the basis of a height SDS below -2, or had a height SDS between -1 and -2 and a predicted adult height SDS below -2. The adolescents and their parents completed questionnaires and a structured interview on the presence of height-related stressors, parental worries about their child's behavior and future prospects, problems in psychosocial functioning, and treatment expectations. Questionnaire scores were compared to norms of the general Dutch population. Results The adolescents reported normal psychosocial functioning and highly positive expectations of the treatment in terms of height gain, whereas the parents reported that their children encountered some behavioral problems (being anxious/depressed, and social and attention problems) and height-related stressors (being teased and juvenilized). About 40% of the parents were worried about their children's future prospects for finding a spouse or job. The motives of the adolescents and their parents exhibited rather different profiles. The most prevalent parental worries related to the current or future functioning of their children, while a few cases were characterized by no observed motives or by psychosocial problems only reported by the adolescents themselves. Conclusion The motives for participating in a growth-enhancing hormone trial are more obvious in the parents than in the adolescents themselves. Two out of three parents report worries about the future opportunities or observe modest current psychosocial problems in their children. The adolescents want to gain height, but the motivation underlying this remains unclear. Few of the adolescents experience psychosocial problems. Our analyses revealed differences among individuals in terms of motives, which implies that in an evaluation of hormone treatment, the importance of divergent outcome variables will also differ among individuals. Effectiveness evaluations of hormone treatment to increase height and the consequential fulfillment of other goals must be awaited

Effects of the noradrenergic agonist clonidine on temporal and spatial attention

Rationale: Recent theories posit an important role for the noradrenergic system in attentional selection in the temporal domain. In contrast, the spatially diffuse topographical projections of the noradrenergic system are inconsistent with a direct role in spatial selection. Objectives: To test the hypotheses that pharmacological attenuation of central noradrenergic activity should (1) impair performance on the attentional blink task, a task requiring the selection of targets in a rapid serial visual stream of stimuli; and (2) leave intact the efficiency of the search for a target in a two-dimensional visuospatial stimulus array. Materials and methods: Thirty-two healthy adult human subjects performed an attentional blink task and a visual search task in a double-blind, placebo-controlled, between-subject study investigating the effects of the α2 adrenoceptor agonist clonidine (150 μg, oral dose). Results: No differential effects of clonidine vs placebo were found on the attentional blink performance. Clonidine slowed overall reaction times in the visual search task but did not impair the efficiency of the visual search. Conclusions: The attentional blink results are inconsistent with recent theories about the role of the noradrenergic system in temporal filtering and in mediating the attentional blink. This discrepancy between theory and data is discussed in detail. The visual search results, in combination with previous findings, suggest that the noradrenergic system is not directly involved in spatial attention processes but instead can modulate these processes in an indirect fashion. © 2007 Springer-Verlag

PDD symptoms in ADHD, an independent familial trait?

The aims of this study were to investigate whether subtle PDD symptoms in the context of ADHD are transmitted in families independent of ADHD, and whether PDD symptom familiality is influenced by gender and age. The sample consisted of 256 sibling pairs with at least one child with ADHD and 147 healthy controls, aged 5-19 years. Children who fulfilled criteria for autistic disorder were excluded. The Children's Social Behavior Questionnaire (CSBQ) was used to assess PDD symptoms. Probands, siblings, and controls were compared using analyses of variance. Sibling correlations were calculated for CSBQ scores after controlling for IQ, ADHD, and comorbid anxiety. In addition, we calculated cross-sibling cross-trait correlations. Both children with ADHD and their siblings had higher PDD levels than healthy controls. The sibling correlation was 0.28 for the CSBQ total scale, with the CSBQ stereotyped behavior subscale showing the strongest sibling correlation (r = 0.35). Sibling correlations remained similar in strength after controlling for IQ and ADHD, and were not confounded by comorbid anxiety. Sibling correlations were higher in female than in male probands. The social subscale showed stronger sibling correlations in elder than in younger sibling pairs. Cross-sibling cross-trait correlations for PDD and ADHD were weak and not-significant. The results confirm that children with ADHD have high levels of PDD symptoms, and further suggest that the familiality of subtle PDD symptoms in the context of ADHD is largely independent from ADHD familiality

Global prevalence of childhood cataract: a systematic review

Childhood cataract is an avoidable cause of visual disability worldwide and is a priority for VISION 2020: The Right to Sight. There is a paucity of information about the burden of cataract in children and the aim of this review is to assess the global prevalence of childhood cataract. The methodology for the review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a literature search for studies reporting estimates of prevalence or incidence of cataract among children (aged<18 years) at any global location using the Cochrane Library, Medline and Embase up to January 2015. No restrictions were imposed based on language or year of publication. Study quality was assessed using a critical appraisal tool designed for systematic reviews of prevalence. Twenty prevalence and four incidence studies of childhood cataract from five different geographical regions were included. The overall prevalence of childhood cataract and congenital cataract was in the range from 0.32 to 22.9/10000 children (median=1.03) and 0.63 to 9.74/10000 (median=1.71), respectively. The incidence ranged from 1.8 to 3.6/10000 per year. The prevalence of childhood cataract in low-income economies was found to be 0.42 to 2.05 compared with 0.63 to 13.6/10000 in high-income economies. There was no difference in the prevalence based on laterality or gender. This review highlights substantial gaps in the epidemiological knowledge of childhood cataract worldwide, particularly from low and lower middle-income economies. More studies are needed using standard definitions and case ascertainment methods with large enough sample sizes

The SMILE study: a study of medical information and lifestyles in Eindhoven, the rationale and contents of a large prospective dynamic cohort study

<p>Abstract</p> <p>Background</p> <p>Health problems, health behavior, and the consequences of bad health are often intertwined. There is a growing need among physicians, researchers and policy makers to obtain a comprehensive insight into the mutual influences of different health related, institutional and environmental concepts and their collective developmental processes over time.</p> <p>Methods/Design</p> <p>SMILE is a large prospective cohort study, focusing on a broad range of aspects of disease, health and lifestyles of people living in Eindhoven, the Netherlands. This study is unique in its kind, because two data collection strategies are combined: first data on morbidity, mortality, medication prescriptions, and use of care facilities are continuously registered using electronic medical records in nine primary health care centers. Data are extracted regularly on an anonymous basis. Secondly, information about lifestyles and the determinants of (ill) health, sociodemographic, psychological and sociological characteristics and consequences of chronic disease are gathered on a regular basis by means of extensive patient questionnaires. The target population consisted of over 30,000 patients aged 12 years and older enrolled in the participating primary health care centers.</p> <p>Discussion</p> <p>Despite our relatively low response rates, we trust that, because of the longitudinal character of the study and the high absolute number of participants, our database contains a valuable set of information.</p> <p>SMILE is a longitudinal cohort with a long follow-up period (15 years). The long follow-up and the unique combination of the two data collection strategies will enable us to disentangle causal relationships. Furthermore, patient-reported characteristics can be related to self-reported health, as well as to more validated physician registered morbidity. Finally, this population can be used as a sampling frame for intervention studies. Sampling can either be based on the presence of certain diseases, or on specific lifestyles or other patient characteristics.</p

Effects of acute treatment with a tryptophan-rich protein hydrolysate on plasma amino acids, mood and emotional functioning in older women

RATIONALE: Effective functioning of the neurotransmitter serotonin is important for optimal cognitive and emotional function. Dietary supplements able to increase availability to the brain of the precursor amino acid, tryptophan (TRP), and thereby enhance serotonin synthesis, can have measurable impact on these psychological processes. OBJECTIVES: This study involves a randomised controlled trial of a TRP-rich egg-white protein hydrolysate (DSM Nutritional Products Ltd., Switzerland) on plasma amino acids, cognition, mood and emotional processing in older women. METHODS: Following a baseline test day without treatment, 60 healthy women aged 45–65 years received drinks containing either 2 or 4 g of TRP-rich protein hydrolysate product or 3.11 g casein hydrolysate as a control. One hour later, they undertook a 2-h battery of cognitive and emotional tests. RESULTS: The TRP-rich protein hydrolysate produced the expected dose-dependent increase in the ratio of plasma TRP to competing large neutral amino acids. TRP-rich protein hydrolysate (2 g only) prevented both the decline in wellbeing and increase in fatigue seen over the test session in the control group. This treatment dose resulted in a significant shift in emotional processing towards positive words and reduced negative bias in assessing negative facial expressions. Effects on cognition were small and not statistically reliable and are not reported here. However, there was no evidence for any adverse effects. CONCLUSIONS: Consumption of a low dose of TRP-rich protein hydrolysate may have beneficial effects on emotional function that could promote feelings of wellbeing, possibly conferring resistance to deterioration in mood in healthy subjects or depressive episodes