No lower cognitive functioning in older adults with attention-deficit/hyperactivity disorder.

BACKGROUND: Research illustrates cognitive deficits in children and younger adults with attention-deficit/hyperactivity disorder (ADHD). Few studies have focused on the cognitive functioning in older adults. This study investigates the association between ADHD and cognitive functioning in older adults. METHODS: Data were collected in a cross-sectional side study of the Longitudinal Aging Study Amsterdam (LASA). A diagnostic interview to diagnose ADHD was administered among a subsample (N = 231, age 60-94). ADHD symptoms and diagnosis were assessed with the Diagnostic Interview for ADHD in Adults (DIVA) 2.0. Cognitive functioning was assessed with tests in the domains of executive functioning, information processing speed, memory, and attention/working memory. RESULTS: Regression analyses indicate that ADHD diagnosis and ADHD severity were only negatively associated with cognitive functioning in the attention/working memory domain. When adjusting for depression, these associations were no longer significant. CONCLUSION: The study shows that ADHD in older adults is associated with lower cognitive functioning in the attention/working memory domain. However, this was partly explained by depressive symptoms.

A Female-Specific Treatment Group for ADHD-Description of the Programme and Qualitative Analysis of First Experiences.

Background: The diagnostics and treatment of attention-deficit/hyperactivity disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period, and (peri)menopause are neglected, even though they impact ADHD symptoms and associated mood disorders. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. Methods: We describe the group programme and underlying rationale, offering a qualitative analysis of the participants' evaluation. Results: The seven bi-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47 years) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable, and the structure suited them well. Completing the premenstrual calendar augmented the awareness and recognition of individual cyclical symptoms. A lifespan approach increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care. Conclusions: Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

The Burden of ADHD in Older Adults: A Qualitative Study.

OBJECTIVE: To explore how ADHD may have affected the lives of older adults who meet the diagnostic criteria of ADHD, but are unaware of their diagnosis. Our second aim was to examine whether the reported symptoms change over the life span. METHOD: A qualitative study was conducted. Seventeen Dutch older people (>65 years) diagnosed in this study with ADHD participated in in-depth interviews. Data were analyzed according to techniques of thematic approach. RESULTS: Seven themes emerged from the analyses. Four themes correspond to ADHD symptoms: "being active," "being impulsive," "attention problems," and "mental restlessness." In addition, the themes "low self-esteem," "overstepping boundaries," and "feeling misunderstood" emerged. The impact of ADHD symptoms seems to have declined with age. CONCLUSION: ADHD has a negative impact on late life, and older adults with the disorder may benefit from treatment. Moreover, this study's findings call for early detection and treatment of ADHD in children and adults.

Efficacy and safety of collagenase treatment for Dupuytren's disease: 2-year follow-up results.

Dupuytren's contracture is a common hand problem that affects the palmar fascia. Several treatment options exist, but none are curative and recurrence is common. Bacterial collagenase has recently been proven beneficial for treating Dupuytren's disease, cleaving the collagen fibers at different sites, with weakening and eventually rupture of the fibrous cords after manipulation. An independent prospective follow-up study was organized on 87 patients, treated with one or more collagenase injections. Inclusion criteria were a contracture of at least 20° at the metacarpophalangeal (MCP) or the proximal interphalangeal (PIP) joint. The most diseased joint was taken into consideration for follow-up evaluation. The resulting extension deficit was measured at 1 month, 1 year and 2 years and was graded as "clinical success", "clinical improvement" or "clinical failure". The mean contracture improved from 45° (39° for MCP and 54° for PIP joints) before treatment to 5° (2° for MCP and 9° for PIP joints) 4 weeks after treatment. No serious complications occurred. After 2 years, 68 joints were evaluated; 61.5% of the MCP joints and 34.5% of the PIP joints had a contracture of ≤20°. When compared with the 4-week evaluation, 28.2% of MCP joints and 62.1% of PIP joints had a recurrence (20° or greater worsening) or had received additional treatment. Collagenase injection is a safe and effective treatment option for Dupuytren disease, but recurrence is common especially for the PIP joint.

Lifetime stability of ADHD symptoms in older adults.

Attention-deficit/hyperactivity disorder (ADHD) has been shown to continue into old age. Studies in children and younger adults show a reduction in hyperactive-impulsive symptoms, whereas the number of inattentive symptoms stays stable. The current study examined the lifetime stability of ADHD symptoms up to old age. Data on ADHD diagnosis and symptoms were collected in a two-phase side-study (N = 231) of the Longitudinal Aging Study Amsterdam. Paired t tests and ANCOVAs were used to analyze the data. Paired t test suggests continuity of the number of reported ADHD symptoms currently present and present in childhood. The change in the balance of inattentive/hyperactive-impulsive symptoms at present and in childhood is also the same in persons with ADHD. Finally, the difference in the change in the balance of inattentive/hyperactive-impulsive symptoms in those with and without ADHD suggests continuity throughout the life span. Our results suggest that diagnostic criteria developed for younger adults may be used among older adults. However, we collected our data retrospectively, which may have biased our results. Future research should follow larger cohorts of patients with ADHD prospectively over the life span.

The role of adverse life events on depression in older adults with ADHD.

BACKGROUND: Comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and depression is high, also in older adults. Thus far it is not well understood why ADHD and depression are so strongly interrelated. One factor that may play a role in older adults with ADHD is an increased risk of experiencing adverse life events. METHODS: Six year follow-up data were used from the Longitudinal Aging Study Amsterdam (LASA). To diagnose ADHD, the DIVA 2.0, a diagnostic interview was administered among a subsample (N=230, age 60-94). In addition to the ADHD diagnosis, the associations between the number of ADHD symptoms, depressive symptoms and adverse life events were examined. Data were analyzed by means of logistic and linear regression analyses. RESULTS: Compared to older adults without ADHD, those with ADHD reported more serious conflicts. The risk of depression in older adults with ADHD was partly explained by serious conflicts. Furthermore, the association between ADHD severity and depression was stronger in those who experienced serious conflicts and those who experienced more adverse life events. LIMITATIONS: The ADHD diagnosis was based on the DSM-IV criteria, which were developed for children, and have not yet been validated in (older) adults. CONCLUSIONS: Having conflicts with others and accumulation of adverse life events over time partly explained the association between ADHD and depression. Better and earlier treatment of ADHD may prevent the development of depression in the presence of life events associated with ADHD.

D-malate production by permeabilized Pseudomonas pseudoalcaligenes; optimization of conversion and biocatalyst productivity.

For the development of a continuous process for the production of solid D-malate from a Ca-maleate suspension by permeabilized Pseudomonas pseudoalcaligenes, it is important to understand the effect of appropriate process parameters on the stability and activity of the biocatalyst. Previously, we quantified the effect of product (D-malate2 -) concentration on both the first-order biocatalyst inactivation rate and on the biocatalytic conversion rate. The effects of the remaining process parameters (ionic strength, and substrate and Ca2 + concentration) on biocatalyst activity are reported here. At (common) ionic strengths below 2 M, biocatalyst activity was unaffected. At high substrate concentrations, inhibition occurred. Ca2+ concentration did not affect biocatalyst activity. The kinetic parameters (both for conversion and inactivation) were determined as a function of temperature by fitting the complete kinetic model, featuring substrate inhibition, competitive product inhibition and first-order irreversible biocatalyst inactivation, at different temperatures simultaneously through three extended data sets of substrate concentration versus time. Temperature affected both the conversion and inactivation parameters. The final model was used to calculate the substrate and biocatalyst costs per mmol of product in a continuous system with biocatalyst replenishment and biocatalyst recycling. Despite the effect of temperature on each kinetic parameter separately, the overall effect of temperature on the costs was found to be negligible (between 293 and 308 K). Within pertinent ranges, the sum of the substrate and biocatalyst costs per mmol of product was calculated to decrease with the influent substrate concentration and the residence time. The sum of the costs showed a minimum as a function of the influent biocatalyst concentration.

Hybridoma and CHO cell partitioning in aqueous two-phase systems.

The partitioning of mouse/mouse hybridoma cell line BIF6A7, mouse/rat hybridoma PFU-83, and CHO DUKX B11-derived cell line BIC-2 in aqueous two-phase systems (ATPSs) of poly(ethylene glycol) (PEG) and dextran was studied. The partitioning of BIF6A7 was investigated systematically by using a statistical experimental design. The aims were to identify the key factors governing cell partitioning and to select ATPSs with suitable cell partitioning for extractive bioconversions with animal cells. The influence of five factors, i.e., the poly(ethylene glycol) molecular weight (PEG MW), dextran molecular weight (Dx MW), tie-line length (TLL), pH, and the ratio of potassium phosphate to potassium chloride, defined as the fraction KPi/(KPi + KCl), on BIF6A7 cell partitioning was characterized by using a full factorial experimental design. The cell partitioning ranged from complete partitioning into the interface to an almost complete partitioning to the lower phase. In all cases less than 1% of the cells partitioned to the top phase. The potassium phosphate fraction had the largest effect on cell partitioning. Low potassium phosphate fractions increased the proportion of cells in the lower phase. To a lesser extent the other factors also played a role in the cell partitioning. The best partitioning for the BIF6A7 cell line was obtained in ATPSs with PEG MW = 35,000, Dx MW = 40,000, TLL = 0.10 g/g, pH 7.4, and KPi/(KPi + KCl) = 0.1, where 93% of the cells were present in the lower phase. The previously reported partitioning of BIF6A7 cells in ATPS culture medium, corresponded well with the current findings. The partitioning of mouse/rat hybridoma cell line PFU-83 and CHO cell line BIC-2 was studied in an ATPS culture medium with PEG 35,000, dextran 40,000, TLL = 0.12 g/g, and hybridoma culture medium. Both cell lines partitioned almost completely into the lower phase. Moreover, the PFU-83 cell line was able to grow in the ATPS hybridoma culture medium. This ATPS hybridoma culture medium therefore seems to be suitable for extractive bioconversions with a wide range of hybridoma cell lines, provided that their product can be partitioned into the upper PEG-rich phase.

Sway regularity reflects attentional involvement in postural control: effects of expertise, vision and cognition.

We examined the time varying (dynamic) characteristics of center-of-pressure (COP) fluctuations in a group of 14 preadolescent dancers and 16 age-matched non-dancers. The task involved maintaining balance for 20s with eyes open or eyes closed, and with or without performing an attention demanding cognitive task (word memorization). The main finding was that the time-dependent structure of the COP trajectories of dancers exhibited less regularity than that of non-dancers, as evidenced by a higher sample entropy (decreased statistical regularity). COP irregularity also increased during secondary task performance but decreased during standing with eyes closed. The combined findings indicate that the degree of attentional involvement in postural control - as reflected in the COP dynamics - varies along an automaticity continuum, and is affected by relatively stable subject characteristics (expertise) and more transient factors related to the attentional requirements of the task at hand.

Growth of Ca-D-malate crystals in a bioreactor.

To develop a bioreactor for solid-to-solid conversions, the conversion of solid Ca-maleate to solid Ca-D-malate by permeabilized Pseudomonas pseudoalcaligenes was studied. In a bioreactor seeded with product (Ca-D-malate) crystals, growth of Ca-D-malate crystals is the last step in the solid-to-solid conversion and is described here. Crystal growth is described as a transport process followed by surface processes. In contrast to the linear rate law obeyed by the transport process, the surface processes of a crystal-growth process can also obey a parabolic or exponential rate law. Growth of Ca-D-malate crystals from a supersaturated aqueous solution was found to be surface-controlled and obeyed an exponential rate law. Based on this rate law, a kinetic model was developed which describes the decrease in supersaturation due to Ca-D-malate crystal growth as a function of the constituent ions, Ca(2+) and D-malate(2-). The kinetic parameters depended on temperature, but, as expected (surface-controlled), they were hardly affected by the stirring speed.

Modeling solid-to-solid biocatalysis: integration of six consecutive steps.

A quantitative model for the conversion of a solid-substrate salt to a solid-product salt in a batch bioreactor seeded with product crystals is presented. The overall process consists of six serial steps (with dissolution and crystallization each in themselves complex multistep processes): solid-salt dissolution, salt dissociation into an ionic substrate and a counter-ion, bioconversion accompanied by biocatalyst inactivation, complexation of the ionic product with the counter-ion, and salt crystal growth. In the model, the consecutive steps are integrated, including biocatalyst inactivation and assuming that salt dissociation and complexation of ions are at equilibrium. Model parameters were determined previously in separate independent experiments. To validate the model, either dissolved or solid Ca-maleate was converted to solid Ca-D-malate by permeabilized Pseudomonas pseudoalcaligenes in a batch bioreactor seeded with Ca-D-malate crystals. The model very well predicted the concentrations of all components in the liquid phase (Ca-maleate, Ca(2+), maleate(2-), D-malate(2-), and Ca-D-malate) and the amounts of the solid phases (Ca-maleate. H(2)O and Ca-D-malate. 3H(2)O), especially when high initial amounts of Ca-maleate. H(2)O and Ca-D-malate. 3H(2)O were present.

IgG and hybridoma partitioning in aqueous two-phase systems containing a dye-ligand.

The effect of the important ATPS- and buffer parameters on IgG and hybridoma partitioning in ATPSs containing a PEG-dye-ligand was studied. Objective was to establish selection criteria for effective ligands for extractive fermentations with animal cells in ATPSs. In the presence of 1% PEG-dye-ligand the binding of IgG to the PEG-ligand was affected severely by the Na-chloride concentration. The tie-line length and pH affected IgG partitioning to a lesser extent. The desired partitioning of IgG into the top phase, was only obtained when, in addition to the 10 mmol/kg K-phosphate buffer, no Na-chloride was present. In an ATPS culture medium, with +/- 35 mmol/kg Na-bicarbonate and 60 mmol/kg Na-chloride, increasing the PEG-dye-ligand concentration up to 100% did increase the partition coefficient, but was not effective in concentrating the IgG in the top phase of ATPS culture medium at a pH of 7.8. Furthermore, addition of the PEG-dye-ligand to ATPS culture medium changed the hybridoma cell partitioning from the bottom phase to the interface.

Separation of hybridoma cells from their IgG product using aqueous two-phase systems.

The partitioning of IgG in aqueous two-phase systems (ATPSs) of PEG and Dextran was studied systematically using a statistical experimental design. Aim was to improve the separation of hybridoma cells and their IgG product, by identifying the key variables governing IgG partitioning, and by comparing the IgG partitioning data with the hybridoma cell partitioning data obtained in previous work. The influence of five factors, i.e. the poly(ethylene glycol) molecular weight (PEG Mw), dextran molecular weight (Dx Mw), tie-line length (TLL), pH and potassium phosphate fraction (KPi/(KPi+KCl)), on IgG partitioning was characterized using a full-factorial experimental design. In all of the ATPS's the IgG partitioned predominantly into the lower phase. The partition coefficient varied between 0.78 (Variable settings: PEG Mw = 6000, Dx Mw = 500000, TLL = 0.10 g g-1, KPi/(KPi+KCl) = 1.0 and pH = 7.4) and 0.0002 (Variable settings: PEG Mw = 35000, Dx Mw = 40000, TLL = 0.20 g g-1 KPi/(KPi+KCl) = 1.0 and pH 6.6). The tie-line length, the dextran molecular weight and the PEG molecular weight had the most pronounced effect on IgG partitioning. Matching the partitioning data of the IgG product with previously obtained data of the hybridoma cell partitioning, showed that within the experimental design no ATPS could be found giving a good separation of the hybridoma cells and their IgG product. There are, however, ATPS's available in which the cells partition to, and grow in the lower dextran-rich phase. To achieve a good separation of the hybridoma cells and their IgG product in these ATPSs, the IgG product has to be specifically extracted into the PEG-rich top phase. For this purpose the use affinity ligands coupled to PEG may offer a solution. Therefore, a number of commercially available dye-resins was screened for their ability to bind the BIF6A7 IgG antibody. The mimetic green 1 A6XL dye-resin was found to bind BIF6A7 IgG. The dye-ligand coupled to PEG was used to manipulate the IgG partitioning in an ATPS. In the presence of the PEG-ligand, the IgG partitioned almost completely to the top phase. The IgG-partition coefficient increased three orders of magnitude, resulting in a 25-fold higher IgG concentration in the top phase than in the bottom phase.