The Course of Neurocognitive Functioning and Prediction of Behavioral Outcome of ADHD Affected and Unaffected Siblings.

Longitudinal studies on the course of neurocognitive functioning of children with ADHD and their unaffected siblings are scarce. Also, it is unclear to what extent that course is related to ADHD outcomes. A carefully phenotyped large sample of 838 Caucasian participants (ADHD-combined type: n = 339, unaffected siblings: n = 271, controls: n = 228; mean age at baseline = 11.4 years, mean age at follow-up = 17.3 years, SD = 3.2) was used to investigate differences in the course of neurocognitive functioning of ADHD affected and unaffected siblings versus controls, and to investigate the relationship between neurocognitive change and ADHD outcomes. At baseline, an aggregated measure of overall neurocognitive functioning and eight neurocognitive measures of working memory, timing (speed/variability), motor control, and intelligence were investigated. Outcomes at follow-up were dimensional measures of ADHD symptom severity and the Kiddie-Global Assessment Scale (K-GAS) for overall functioning. At follow up, affected and unaffected siblings trended to, or fully caught up with performance levels of controls on four (44.4%) and five (55.6%) of the nine dependent variables, respectively. In contrast, performance in remaining key neurocognitive measures (i.e. verbal working memory, variability in responding) remained impaired at follow-up. Change in neurocognitive functioning was not related to ADHD outcomes. Our results question the etiological link between neurocognitive deficits and ADHD outcomes in adolescents and young adults.

The Effectiveness of a PRoactive Multicomponent Intervention Program on Disability in Independently Living Older People: A Randomized Controlled Trial.

BACKGROUND: There is an increase in functional limitations and a decline in physical and mental well-being with age. Very few effective lifestyle interventions are available to prevent adverse outcomes such as disability in (pre-) frail older people. The effectiveness of an interdisciplinary multicomponent intervention program to prevent disability in older people in the community was tested. METHOD: A randomized controlled trial (RCT) with a one-year follow-up was conducted in the Netherlands. Community-dwelling pre-frail older people aged 65 years and over were invited to participate. Frailty was measured with the Groningen Frailty Indicator (GFI) and categorized into non-frail (GFI=0), pre-frail (GFI = 1-3) and frail (GFI ≥ 4). The intervention program consisted of four components: a medication review, physical fitness, social skills, and nutrition. OUTCOMES: The primary outcome was activity of daily living (ADL) measured with the Katz-6. Secondary outcomes were quality of life (SF-12) and healthcare consumption such as hospital admission, nursing home admission and primary care visits. Additional outcomes measured in the intervention group were physical fitness, Instrumental Activities of Daily Living (IADL), muscle strength, walking speed, functional capacity, mobility, feelings of depression and loneliness and nutritional status. The data were collected at baseline, after each intervention component and at a 12-month follow-up. An intention to treat analysis was used. RESULTS: In total, there were 290 participants, and 217 (74.8%) completed the study. The mean age was 74 (SD: 7.2), most were pre-frail (59.9%), the majority were female (55.2%), and the individuals were not living alone (61.4%). After the 12-month follow-up, the median Katz-6 score did not change significantly between the two groups; adjusted Odds Ratio (OR) = 0.96 (95% Confidence Interval (CI): 0.39-2.35, p-value 0.92). No statistically significant differences were observed between the groups for quality of life and healthcare consumption. Among the participants in the intervention group, IADL (Friedman's test p <=0.04, X2 =6.50), walking speed (Friedman's test p <0.001, X2 =19.09) and functional capacity (Friedman's test p <0.001, X2 =33.29) improved significantly after the one-year follow-up. Right-hand grip strength improved immediately after completion of the intervention (Wilcoxon signed-rank test p=0.00, z= -3.39) but not after the 12-month follow-up. CONCLUSION: The intervention program did not significantly improve daily functioning, quality of life and healthcare consumption among (pre) frail community-dwelling older persons at the one-year follow-up. Participants in the intervention group experienced improvements in walking speed, functional capacity and instrumental activities of daily living. More research is needed to better understand why may benefit and how to identify the target population.

Attention deficit hyperactivity disorder (ADHD) and executive functioning in affected and unaffected adolescents and their parents: challenging the endophenotype construct.

BACKGROUND: The results of twin and sibling studies suggest that executive functioning is a prime candidate endophenotype in attention deficit hyperactivity disorder (ADHD). However, studies have not assessed the co-segregation of executive function (EF) deficits from parents to offspring directly, and it is unclear whether executive functioning is an ADHD endophenotype in adolescents, given the substantial changes in prefrontal lobe functioning, EF and ADHD symptoms during adolescence. METHOD: We recruited 259 ADHD and 98 control families with an offspring average age of 17.3 years. All participants were assessed for ADHD and EF [inhibition, verbal (VWM) and visuospatial working memory (VsWM)]. Data were analysed using generalized estimating equations (GEEs). RESULTS: Parental ADHD was associated with offspring ADHD and parental EF was associated with offspring EF but there were no cross-associations (parental ADHD was not associated with offspring EF or vice versa). Similar results were found when siblings were compared. EF deficits were only found in affected adolescents and not in their unaffected siblings or (un)affected parents. CONCLUSIONS: The core EFs proposed to be aetiologically related to ADHD, that is working memory and inhibition, seem to be aetiologically independent of ADHD in adolescence. EF deficits documented in childhood in unaffected siblings were no longer present in adolescence, suggesting that children 'grow out' of early EF deficits. This is the first study to document ADHD and EF in a large family sample with adolescent offspring. The results suggest that, after childhood, the majority of influences on ADHD are independent from those on EF. This has potential implications for current aetiological models of causality in ADHD.

Does neurocognitive functioning predict future or persistence of ADHD? A systematic review.

Many children with ADHD remain symptomatic in (young) adulthood. It is important to understand what characterizes this persistent ADHD group. Since ADHD has been associated with neurocognitive dysfunctioning on a variety of neurocognitive domains, and many of these domains are influenced by the same risk genes that influence ADHD, neurocognitive functions are a potential predictor for ADHD persistence. We carried out a systematic literature review on the predictive value of neurocognitive functioning for future ADHD. Based on eighteen studies there was no evidence that either automatically controlled (requiring little mental effort; lower level), or more consciously controlled (requiring high levels of mental effort; higher level) neurocognitive functions differentiated ADHD persistence from remittance. In general, both persisters and remitters showed weaker performance than typically developing controls, although the effect was smaller for remitters. Neurocognitive functions measured in childhood predicted ADHD a few years later, regardless of the type of neurocognitive function. Our findings do not support the model of Halperin and Schulz (2006), which suggests a maturation of more consciously controlled neurocognitive functions in ADHD remitters.

Measures of body composition and risk of heart failure in the elderly: the Rotterdam study.

OBJECTIVES: The incidence of heart failure increases with aging. Aim of the present study was to determine whether measures body composition predict incident heart failure in older adults. SETTING: Prospective community-based cohort study. 5, 868 men and women aged 55 years and older participating the Rotterdam study. Measures of body mass index and waist circumference were obtained at baseline. Information on incident heart failure was obtained during follow-up. Cox regression analyses were performed to investigate the possible association between measure of body composition and incident heart failure. RESULTS: During a mean follow up of 10.9 (SD ±4.4) years, 765 participants had heart failure. After adjustment for age and gender, 1-standard deviation of body mass index, waist circumference and the waist-hip ratio predicted heart failure (HR 1.25; 95% CI 1.17-1.34; HR 1.26; 95% CI 1.18-1.36; and HR 1.17; 95% CI 1.08-1.27), respectively. In age-stratified analyses, 1-standard deviation of body mass index (1.17; 95% CI 1.06- 1.29) and waist circumference (1.16; 95% CI 1.05- 1.29) were still associated with the risk of heart failure in the oldest participants, whereas the waist-hip ratio was not (1.06; 95% CI 0.945-1.18). CONCLUSION: Although estimates decrease with age, measures of overall and central adiposity predict incident heart failure among community dwelling older adults.

Host defence during Klebsiella pneumonia relies on haematopoietic-expressed Toll-like receptors 4 and 2.

In this study, the relative roles of Toll-like receptor (TLR)2 and TLR4 were investigated independently and together. Moreover, we studied the role of haematopoietic compartment in anti-Klebsiella host defence. We infected TLR2 and TLR4 single-, and TLR2×4 double knockout (KO) animals with different doses of Klebsiella pneumoniae. In addition, bone marrow chimeric mice were created and infected. TLR4 played a more prominent role in antibacterial defence than TLR2, considering that only TLR4 KO mice demonstrated enhanced bacterial growth in lungs and spleen 24 h after infection with 3×10³ colony-forming units of Klebsiella compared with wild-type (WT) mice. In late-stage infection or after exposure to a higher infectious dose, bacterial counts in lungs of TLR2 KO animals were elevated compared with WT mice and TLR2×4 KO animals were more susceptible to infection than TLR4 KO mice. TLR signalling in cells of haematopoietic origin is of primary importance in host defence against K. pneumoniae. These data suggest that: 1) TLR4 drives the antibacterial host response after induction of pneumonia with relatively low Klebsiella doses; 2) TLR2 becomes involved at a later phase of the infection and/or upon exposure to higher bacterial burdens; and 3) haematopoietic TLR2 and TLR4 are important for an adequate host response during Klebsiella pneumonia.

Tumor necrosis factor-alpha inhibition protects against endotoxin-induced endothelial glycocalyx perturbation.

OBJECTIVE: Inflammatory stimuli profoundly increase the vulnerability of the vessel wall to atherogenesis. The endothelial glycocalyx, a layer of glycosaminoglycans and proteoglycans covering the luminal side of the vasculature, has recently emerged as an orchestrator of vascular homeostasis. In the present study, we investigated whether endotoxin-induced inflammatory reactions lead to a decrease of endothelial glycocalyx thickness in humans and whether tumor necrosis factor-alpha (TNFalpha) plays a role in this process. DESIGN, SUBJECTS AND INTERVENTION: Healthy male volunteers received low-dose endotoxin (1ng/kg) intravenously, with (n=8) or without (n=13) pre-treatment with the soluble TNFalpha receptor etanercept. Endothelial glycocalyx thickness and related parameters were determined after endotoxin challenge. RESULTS: Endotoxin resulted in a profound reduction in microvascular glycocalyx thickness (from 0.60+/-0.1 to 0.30+/-0.1microm, p<0.01). Concomitantly, plasma levels of the principal glycocalyx constituent hyaluronan (62+/-18 to 85+/-24ng/mL, p<0.05), monocyte activation and coagulation activation increased (F1+2; 0.3+/-0.1 to 2.8+/-1.5nmol/L, p<0.05 and d-dimer; from 0.2+/-0.1 to 0.4+/-0.1mg/L, p<0.05 compared to baseline). Inhibition of TNFalpha by etanercept attenuated loss of microvascular glycocalyx thickness (0.54+/-0.1 to 0.35+/-0.1mum, p<0.05). Changes in hyaluronan (58+/-13 to 46+/-10ng/mL, p<0.05) and coagulation activation were also attenuated (F1+2; 0.3+/-0.1 to 2.1+/-0.9nmol/L and d-dimer; from 0.2+/-0.1 to 0.3+/-0.1mg/L, p<0.05 compared to baseline). CONCLUSIONS: These data suggest that inflammatory activity, in part mediated by TNFalpha, leads to perturbation of the endothelial glycocalyx in humans. This may contribute to the vascular vulnerability induced by inflammation.

Depth map calculation for a variable number of moving objects using markov sequential object processes.

We advocate the use of Markov sequential object processes for tracking a variable number of moving objects through video frames with a view towards depth calculation. A regression model based on a sequential object process quantifies goodness of fit; regularization terms are incorporated to control within and between frame object interactions. We construct a Markov chain Monte Carlo method for finding the optimal tracks and associated depths and illustrate the approach on a synthetic data set as well as a sport sequence.

Sodium iron (III) ethylenediaminetetraacetic acid synthesis to reduce iron deficiency globally.

Despite major interest in sodium iron (III) ethylenediaminetetraacetic acid's (EDTA) potential use in food fortification programs in potentially curbing the global problem of iron deficiency and its anemia, synthesis methods of stable isotope-labeled sodium iron (III) EDTA for use in human bioavailability studies are incomplete, incorrect or totally lacking. Owing to a number of clinical research groups requiring this compound in bioavailability studies, in both developing and already developed countries, we simplified and optimized the synthesis of sodium iron (III) EDTA from a block of isotopically enriched iron metal, in order that it be easily reproduced, cheaply, using simple basic laboratory apparatus. The resulting product is of high purity (>99.0%), and may be used for human stable isotope bioavailability studies. The simplicity of this method allows for the many research groups, currently doing such studies, to perform their own syntheses. Additionally, more uniformity in this synthesis will reduce the variation observed between such studies.

Electrospinning versus knitting: two scaffolds for tissue engineering of the aortic valve.

Two types of scaffolds were developed for tissue engineering of the aortic valve; an electrospun valvular scaffold and a knitted valvular scaffold. These scaffolds were compared in a physiologic flow system and in a tissue-engineering process. In fibrin gel enclosed human myofibroblasts were seeded onto both types of scaffolds and cultured for 23 days under continuous medium perfusion. Tissue formation was evaluated by confocal laser scanning microscopy, histology and DNA quantification. Collagen formation was quantified by a hydroxyproline assay. When subjected to physiologic flow, the spun scaffold tore within 6 h, whereas the knitted scaffold remained intact. Cells proliferated well on both types of scaffolds, although the cellular penetration into the spun scaffold was poor. Collagen production, normalized to DNA content, was not significantly different for the two types of scaffolds, but seeding efficiency was higher for the spun scaffold, because it acted as a cell impermeable filter. The knitted tissue constructs showed complete cellular in-growth into the pores. An optimal scaffold seems to be a combination of the strength of the knitted structure and the cell-filtering ability of the spun structure.

Bioefficacy of beta-carotene dissolved in oil studied in children in Indonesia.

BACKGROUND: More information on the bioefficacy of carotenoids in foods ingested by humans is needed. OBJECTIVE: We aimed to measure the time required for isotopic enrichment of beta-carotene and retinol in serum to reach a plateau, the extent of conversion of beta-carotene dissolved in oil with use of beta-carotene and retinol specifically labeled with 10 (13)C atoms, and the intraindividual variation in response. DESIGN: Indonesian children aged 8--11 y (n = 35) consumed 2 capsules/d, 7 d/wk, for < or =10 wk. Each capsule contained 80 microg [12,13,14,15,20,12',13',14',15',20'-(13)C(10)]beta-carotene and 80 microg [8,9,10,11,12,13,14,15,19,20-(13)C(10)]retinyl palmitate. Three blood samples were drawn per child over a period of < or =10 wk. HPLC coupled with atmospheric pressure chemical ionization liquid chromatography-mass spectrometry was used to measure the isotopic enrichment in serum of retinol with [(13)C(5)]retinol and [(13)C(10)]retinol and of beta-carotene with [(13)C(10)]beta-carotene. The beta-carotene in the capsules used had a cis-trans ratio of 3:1. RESULTS: Plateau isotopic enrichment was reached by day 21. The amount of beta-carotene in oil required to form 1 microg retinol was 2.4 microg (95% CI: 2.1, 2.7). The amount of all-trans-beta-carotene required to form 1 microg retinol may be lower. CONCLUSIONS: The efficiency of conversion of this beta-carotene in oil was 27% better than that estimated previously (1.0 microg retinol from 3.3 microg beta-carotene with an unknown cis-trans ratio). The method described can be extended to measure the bioefficacy of carotenoids in foods with high precision, requiring fewer subjects than other methods.

A liquid chromatography-mass spectrometry method for the quantification of bioavailability and bioconversion of beta-carotene to retinol in humans.

A method based on high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (APCI LC-MS) was developed for the quantification of the bioavailability of retinyl palmitate and beta-carotene and the bioconversion of beta-carotene to retinol in humans. Following oral administration of [8,9,10,11,12,13,14,15,19,20-13C10]-retinyl palmitate and [12,13,14,15,20,12',13',14',15',20'-13C10]-beta-carotene at physiological doses to children between 8 and 11 years of age, blood samples were drawn and serum was prepared. Retinol and beta-carotene were extracted from 0.2- and 1.0-mL serum samples, respectively, and analyzed using reversed-phase HPLC with a C30 column interfaced to an APCI mass spectrometer. Unlike other LC-MS assays for carotenoids, no additional purification steps were necessary, nor was any derivatization of retinol or beta-carotene required. APCI LC-MS showed a linear detector response for beta-carotene over 4 orders of magnitude. Using selected ion monitoring to record the elution profile of protonated circulating beta-carotene at m/z 537 and [13C10]-beta-carotene at m/z 547, the limit of detection was determined to be 0.5 pmol injected on-column. To assess the ratio of labeled to unlabeled retinol, selected ion monitoring was carried out at m/z 269, 274, and 279. These abundant fragment ions corresponded to the loss of water from the protonated molecule of circulating retinol, [13C5]-retinol (metabolically formed from orally administered [13C10]-beta-carotene), and [13C10]-retinol (formed by hydrolysis of [13C10]-retinyl palmitate). The ratios of labeled to unlabeled retinol and the ratio of labeled to unlabeled beta-carotene were calculated. Combined with standard HPLC measurement of beta-carotene and retinol concentration and a mathematical model, these results showed that this simple LC-MS method can be used to quantify beta-carotene bioavailability and its bioconversion to retinol at physiologically relevant doses.

Determination of phenolic derivatives of antipyrine in plasma with solid-phase extraction and high-performance liquid chromatography-atmospheric-pressure chemical ionization mass spectrometry.

This manuscript describes a method to determine antipyrine and its phenolic derivatives in plasma by reversed-phase high-performance liquid chromatography-mass spectrometry (RP-HPLC-MS). The sample pretreatment consisted of a C18 solid-phase extraction (SPE), to remove the salts and proteins. The retention behavior of antipyrine and its phenolic derivatives in the SPE procedure was estimated by the k values determined on a C18 HPLC column at different pH values and with different buffer compositions. Recoveries of antipyrine and its phenolic products were 90% in water and 100% in plasma. Atmospheric pressure chemical ionization (APCI) was used to introduce the components into the mass spectrometer. The mass spectrometer was operated in the single ion monitoring mode (SIM mode) as well as in the selective reaction (SR) mode. The SR mode or tandem MS resulted in the best signal-to-noise ratio, with a detection limit for antipyrine of 6 pg in 20 microl. For the different phenolic antipyrines, different target ions were used and conditions were optimized for each.

Development of a method for quantitation of retinol and retinyl palmitate in human serum using high-performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry.

A method for the quantitative analysis of the vitamin A compounds all-trans-retinol and all-trans-retinyl palmitate was developed using high-performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (APCI-LC-MS). Unlike previous quantitative mass spectrometric methods for vitamin A, HPLC separations were carried out using a C30 reversed-phase column instead of GC separation. Because no sample hydrolysis or derivatization was necessary, retinyl palmitate was preserved for analysis instead of being hydrolyzed to retinol. Human serum was analyzed following simple hexane extraction without saponification or any additional purification. A comparison of APCI and electrospray ionization showed that only APCI produced a linear response over all four orders of magnitude of retinol and three orders of magnitude of retinyl palmitate concentrations. Selected ion monitoring of the fragment ion of m/z 269 was used for APCI quantitation of both retinol and retinyl palmitate, since it was the base peak and the only abundant ion in the mass spectra of both compounds and the internal standard, retinyl acetate. The ion of m/z 269 corresponded to loss of water, loss of palmitic acid, or elimination of acetic acid from the protonated molecules of retinol, retinyl palmitate and retinyl acetate, respectively. The limit of detection of APCI-LC-MS for all-trans-retinol and all-trans-retinyl palmitate was determined to be approximately 34 fmol/microliter and 36 fmol/microliter (0.670 pmol all-trans-retinol and 0.720 pmol all-trans-retinyl palmitate injected in 20 microliters on-column), respectively. The limit of quantitation was approximately 500 fmol/microliter and 250 fmol/microliter (10 pmol and 5 pmol injected in 20 microliters on-column) for retinol and retinyl palmitate, respectively.

Leather nights in the woods: homosexual encounters in a Dutch highway rest area.

This article describes a small-scale research on homosexual encounters in a Dutch highway rest area called "the Mollebos." Research was carried out on Monday evenings and nights, the so-called "leather nights," which attracted a specific group of patrons: men into leathersexuality and sadomasochism (S&M). Participant observation, informal conversations, and in-depth interviews made it possible to analyze spatial strategy as used by cruising men and the individual meanings patrons attach to outdoor leather cruising. It was found that in the Netherlands cruisers are no longer members of "a silent community." The leather nights in the woods proved to be an important supplement for the Dutch gay leather and S&M scene. For many visitors they served as an erotic space to realize sexual fantasies.

Pregnancy diagnosis in pigs: a field study comparing linear-array real-time ultrasound scanning and amplitude depth analysis.

Between days 24 and 32 after mating/insemination, 881 pigs (785 pregnant and 96 not-pregnant) were tested for pregnancy on a commercial farm with a linear-array real-time ultrasound scanner. 5-7 Days later, 785 of these animals (708 pregnant and 77 not-pregnant) were tested again with A-mode equipment by farm employees. Confirmation of pregnancy was based on recorded farrowings or abortions; confirmation of non-pregnancy was based on return to oestrus and rebreeding, recorded non-farrowing, or inspection of the uterus of culled animals at the slaughterhouse. From the number of correct positive (a), incorrect positive (b), correct negative (c) and incorrect negative (d) diagnoses, a sensitivity (a/a + d) of 100% versus 97.5%, a specificity (c/c + b) of 90.6 versus 55.8%, a positive predictive value (a:a + b) of 98.9% versus 95.3% and a negative predictive value (c:c + d) of 100% versus 70.5% were calculated for the real-time ultrasound technique versus A-mode technique. It was concluded that real-time ultrasound scanning provides a very accurate technique for pregnancy diagnosis in pigs, enabling immediate decision making on treatment or culling of animals diagnosed as non-pregnant.