Simulation of Micro-Electronic FlowFET Systems

A microelectronic fluidic system has been investigated by modeling and 3D simulation of fluid flow controlled by an applied gate voltage. The simulations have helped to characterize a novel FlowFET (a fluidic Field Effect Transistor) device under fault-free conditions. The FlowFET operates by applying a voltage field from a gate electrode in the insulated side wall of a microchannel to modulate the ␣-potential at the shear plane [1]. The change in ␣-potential can be used to control both the magnitude and direction of the electroosmotic flow in the microchannel

Skin tests, T cell responses and self-reported symptoms in children with allergic rhinitis and asthma due to house dust mite allergy

Abstract BACKGROUND: In allergic responses, a distinction is made between an early-phase response, several minutes after allergen exposure, and a late-phase response after several hours. During the late phase, eosinophils and T cells infiltrate the mucosa and play an important role in inflammation. OBJECTIVE: The aim of this study was to examine the relationship between allergen-induced late-phase skin responses and in vitro T cel

Development of a practical guideline for person centred goal setting in geriatric rehabilitation:A participatory action research

PurposeTo improve goal setting in Geriatric Rehabilitation (GR), by developing an evidence-based practical guideline for patient-centred goal setting.MethodsParticipatory action research (PAR) in a cyclical process, with GR professionals as co-researchers. Each cycle consisted of five phases: problem analysis, literature review, development, practical experience, feedback & evaluation. The evaluation was based on video recordings of goal setting conversations, and on oral and written feedback of the GR professionals who tested the guideline.ResultsIn two PAR-cycles the guideline was developed, consisting of eight recommendations for setting and using goals, and of practical advices elaborating three of the recommendations, concerning conversational skills specific for goal setting conversations. After the second cycle the research team concluded that the guideline was feasible in daily practice and effective when used consciously.ConclusionIn this study, a practical guideline for setting and using goals in GR was developed. GR teams can improve their patient centred working with goals by discussing the recommendations in their team and choosing the recommendations to work on. This can be supported by the development of an interdisciplinary training. The effect on quality of care should be subject to further investigation

Protocol of the Double-Click Seq Method to Evaluate the Deposition Bias of Chromatin Proteins

Symmetrical deposition of parental and newly synthesized chromatin proteins over both sister chromatids is important for the maintenance of epigenetic integrity. However, the mechanisms to maintain equal distribution of parental and newly synthesized chromatid proteins over sister chromatids remains largely unknown. Here, we describe the protocol for the recently developed double-click seq method that enables mapping of asymmetry in the deposition of parental and newly synthesized chromatin proteins on both sister chromatids in DNA replication. The method involved metabolic labeling of new chromatin proteins with l-Azidohomoalanine (AHA) and newly synthesized DNA with Ethynyl-2′-deoxyuridine (EdU) followed by two subsequent click reactions for biotinylation and subsequently by corresponding separation steps. This enables isolation of parental DNA that was bound to nucleosomes containing new chromatin proteins. Sequencing of these DNA samples and mapping around origins of replication in the cellular DNA enables estimation of the asymmetry in deposition of chromatin proteins over the leading and lagging strand in DNA replication. Altogether, this method contributes to the toolbox to understand histone deposition in DNA replication.</p

Prognosis and Survival of Older Patients With Dizziness in Primary Care:a 10-year prospective cohort study

Purpose: The prognosis of dizzy older patients in primary care is unknown. Our objective was to determine the prognosis and survival of patients with different subtypes and causes of dizziness. Methods: In a primary care prospective cohort study, 417 older adults with dizziness (mean age 75.5 years) received a full diagnostic workup in 2006-2008. A panel of physicians classified their dizziness subtype and primary cause of dizziness. Presyncope was the most common dizziness subtype (69.1%), followed by vertigo (41.0%), disequilibrium (39.8%), and other dizziness (1.7%). The most common primary causes of dizziness were cardiovascular disease (56.8%) and peripheral vestibular disease (14.4%). Main outcome measures were mortality and dizziness-related impairment assessed at 10-year follow-up.Results: At 10-year follow-up 169 patients (40.5%) had died. Multivariable adjusted Cox models showed a lower mortality rate for patients with the subtype vertigo compared to other subtypes (HR 0.62 (95% CI 0.40 to 0.96)), and for peripheral vestibular disease versus cardiovascular disease as primary cause of dizziness (HR 0.46 (95% CI 0.25 to 0.84)). After 10 years, 47.7% of patients who filled out the follow-up measurement experienced substantial dizziness-related impairment. No significant difference in substantial impairment was seen between different subtypes and primary causes of dizziness. Conclusions: The 10-year mortality rate was lower for the dizziness subtype vertigo compared to other subtypes. Patients with dizziness primarily caused by peripheral vestibular disease had a lower mortality rate than patients with cardiovascular disease. Substantial dizziness-related impairment in older dizzy patients 10 years later is high, and indicates that current treatment strategies by FPs may be suboptimal.<br/

Modeling of Micro-Electronic Fluidic Systems

A microelectronic fluidic system is studied using modeling and simulation of fluid flow controlled by applying gate voltage. 2D simulations were used to characterize the fluidic Field Effect Transistor (FlowFET) device under fault-free conditions. The FlowFET operates by applying a voltage from a gate electrode in the insulated side wall of a microchannel, to modulate the z-potential at the shear plane. The change in z-potential can be used to control both the magnitude and the direction of the electroosmotic flow in the microchannel

Induced protein degradation of histone deacetylases 3 (HDAC3) by proteolysis targeting chimera (PROTAC)

Histone deacetylases (HDACs) play important roles in inflammatory diseases like asthma and chronic obstructive pulmonary disease (COPD). Unravelling of and interfering with the functions of specific isoenzymes contributing to inflammation provides opportunities for drug development. Here we synthesize proteolysis targeting chimeras (PROTACs) for degradation of class I HDACs in which o-aminoanilide-based class I HDAC inhibitors are tethered to the cereblon ligand pomalidomide. One of these PROTACs, denoted HD-TAC7, showed promising degradation effects for HDAC3 with a DC50 value of 0.32 μM. In contrast to biochemical evidence using siRNA, HD-TAC7 showed a minimal effect on gene expression in LPS/IFNγ-stimulated RAW 264.7 macrophages. The lack of effect can be attributed to downregulation of the NF-κB subunit p65, which is a known side effect of pomalidomide treatment. Altogether, we describe a novel PROTAC that enables selective downregulation of HDAC3 levels, however we note that concomitant downregulation of the NF-κB subunit p65 can confound the biological outcome

Longitudinal associations of multiple physical symptoms with recurrence of depressive and anxiety disorders

Objective To examine longitudinal associations of multiple physical symptoms with recurrence of depressive and anxiety disorders. Methods Follow-up data of 584 participants with remitted depressive or anxiety disorders were used from the Netherlands Study of Depressive and Anxiety disorders. Multiple physical symptoms were measured at baseline (T1) and two-year follow-up (T2) by the Four-Dimensional Symptom Questionnaire (4DSQ) somatization subscale. Recurrence of depressive and anxiety disorders was assessed at two-year (T2) and four-year (T4) follow-up with the Composite International Diagnostic Interview. Logistic Generalized Estimating Equations were used to examine associations of multiple physical symptoms with recurrence of depressive and anxiety disorders. Depressive (IDS-SR) and anxiety symptoms (BAI), and other relevant covariates were taken into account. Results Multiple physical symptoms were significantly associated with recurrence of depression (OR = 1.04, 95%CI = 1.00–1.08), anxiety (OR = 1.07, 95%CI = 1.03–1.12), and depressive or anxiety disorders (OR = 1.06, 95%CI = 1.02–1.10), on average over time. Odds ratios did not change substantially when the IDS-SR mood-cognition and BAI subjective scale were included as covariates. Conclusion The presence of multiple physical symptoms was positively related to recurrence of depressive and anxiety disorders, independent of depressive and anxiety symptoms. Knowledge of risk factors for recurrence of depressive and anxiety disorders, such as the presence of multiple physical symptoms, could provide possibilities for better targeting interventions to prevent recurrence

Evaluation of clinical and immunological responses: A 2-year follow-up study in children with allergic rhinitis due to house dust mite

Background. Allergic rhinitis is a disease with polarization towards Thand a defect of regulatory T cells. Immunological changes have been reported after immunotherapy treatment. However, there is not much known about the natural course of allergic rhinitis with respect to clinical manifestation and the relation with immunological responses. Objective. To evaluate clinical symptoms of allergic rhinitis, in relation to in vivo allergen-specific skin responses and in vitro allergen-specific effector and regulatory T cells determined at baseline and after two years. Methods. From a large trial, 59 children were randomly selected. The following variables were compared: clinical symptoms, allergen skin tests, specific IgE, T-cell proliferation, IL-5, IL-13, IFN-gamma, IL-10, TGF-beta, CD 4 + CD 25 hi cells, and Foxp3 expression. Results. Allergic symptoms had decreased after two years. Whereas skin test reactions correlated between years 0 and 2, there was no change in the size of the reaction. Also, proinflammatory reactions did not change after two years, with a positive correlation between years 0 and 2. No relevant changes were observed with respect to regulatory cells. Conclusion. Whereas, comparable to immunotherapy, allergic complaints decrease, the immunological changes of specific T-cell activity (both effector cells and regulator cells) which are observed after immunotherapy, do not change

Internet based vestibular rehabilitation with and without physiotherapy support for adults aged 50 and older with a chronic vestibular syndrome in general practice:three armed randomised controlled trial

Objective: To investigate the clinical effectiveness and safety of stand alone and blended internet based vestibular rehabilitation (VR) in the management of chronic vestibular syndromes in general practice.Design: Pragmatic, three armed, parallel group, individually randomised controlled trial.Setting: 59 general practices in the Netherlands.Participants: 322 adults aged 50 and older with a chronic vestibular syndrome.Interventions: Stand alone VR comprising a six week, internet based intervention with weekly online sessions and daily exercises (10-20 minutes a day). In the blended VR group, the same internet based intervention was supplemented by face-to-face physiotherapy support (home visits in weeks 1 and 3). Participants in the usual care group received standard care from a general practitioner, without any restrictions.Main outcome measures: The primary outcome was vestibular symptoms after six months as measured by the vertigo symptom scale-short form (VSS-SF range 0-60, clinically relevant difference ≥3 points). Secondary outcomes were dizziness related impairment, anxiety, depressive symptoms, subjective improvement of vestibular symptoms after three and six months, and adverse events.Results: In the intention-to-treat analysis, participants in the stand alone and blended VR groups had lower VSS-SF scores at six months than participants in the usual care group (adjusted mean difference −4.1 points, 95% confidence interval −5.8 to −2.5; and −3.5 points, −5.1 to −1.9, respectively). Similar differences in VSS-SF scores were seen at three months follow-up. Participants in the stand alone and blended VR groups also experienced less dizziness related impairment, less anxiety, and more subjective improvement of vestibular symptoms at three and six months. No serious adverse events related to online VR occurred during the trial.Conclusion: Stand alone and blended internet based VR are clinically effective and safe interventions to treat adults aged 50 and older with a chronic vestibular syndrome. Online VR is an easily accessible form of treatment, with the potential to improve care for an undertreated group of patients in general practice.Trial registration: Netherlands Trial Register NTR5712