The environmental burden of inhalation.

Inhalation systems, mostly metered dose inhalers (MDIs) and dry powder inhalers (DPIs), are currently submitted to a critical assessment for their carbon footprint (CF) and environmental impact. They are related to greenhouse gas (GHG) emissions and they produce waste of used devices with withheld drug residues and unused doses. However, with estimated contributions to anthropogenic GHG-emissions of 0.

The fusicoccin story revisited.

Fusicoccin (FC) is one of the most studied fungal metabolites to date. The finding that the plasma membrane H+-ATPase in combination with 14-3-3 proteins acts as a high-affinity receptor for FC was a breakthrough in the field. Ever since, the binding of FC to the ATPase-14-3-3 receptor complex has taken center stage in explaining all FC-induced physiological effects.

[The involvement of older adults in the residential care: dilemmas, pitfalls and potentials].

In the residential care sector we have witnessed throughout the previous decades a development from a rather paternalistic approach towards a more democratic way of care giving. In many care organizations, however, residents are still rarely involved in the daily routine. In a participatory study on a somatic care unit in the Netherlands, we examined the challenges around the involvement of residents in the care residence.

Fusicoccin-A Targets Cancerous Inhibitor of Protein Phosphatase 2A by Stabilizing a C-Terminal Interaction with 14-3-3.

The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein found overexpressed in many types of cancer. CIP2A has been shown to stabilize oncoproteins such as cMYC by shielding them from PP2A-mediated dephosphorylation. Here we report that the penultimate residue Ser904 in the C-terminus of CIP2A can be phosphorylated to create a binding site for the regulatory protein 14-3-3.

Research and Innovation for and with Adolescent Young Carers to Influence Policy and Practice-The European Union Funded "ME-WE" Project.

Young carers are children and adolescents who provide care to other family members or friends, taking over responsibilities that are usually associated with adulthood. There is emerging but still scarce knowledge worldwide about the phenomenon of young carers and the impact of a caring role on their health, social and personal development spheres. This paper provides an overview of the main results from the ME-WE project, which is the first European research and innovation project dedicated to adolescent young carers (AYCs) (15-17 years).

Dry powder inhalation, part 2: the present and future.

Introduction: The manufacture of modern dry powder inhalers (DPIs), starting with the Spinhaler (Fisons) in 1967, was only possible thanks to a series of technological developments in the 20 century, of which many started first around 1950. Not until then, it became possible to design and develop effective, cheap and mass-produced DPIs. The link between these technological developments and DPI development has never been presented and discussed before in reviews about the past and present of DPI technology.

Dry powder inhalation, part 1: ancient history and precursors to modern dry powder inhalers.

Introduction: Inhalation of herbs and other compounds has a long history but habits for medical treatment are intertwined with rituals to obtain hallucinatory effects and pleasurable sensations. Several examples of inhaled herbs, and the diseases they were used for, based on early translations of ancient manuscripts related to inhalation were found to be speculative and inconsistent with each other in literature. They needed to be reconsidered and verified with the original sources of information.

Fragment Screening Yields a Small-Molecule Stabilizer of 14-3-3 Dimers That Modulates Client Protein Interactions.

The development of protein-protein interaction (PPI) inhibitors has been a successful strategy in drug development. However, the identification of PPI stabilizers has proven much more challenging. Here we report a fragment-based drug screening approach using the regulatory hub-protein 14-3-3 as a platform for identifying PPI stabilizers.

Quality of Life of Schoolchildren Living with a Long-Term Sick Parent: The Role of Tasks at Home, Life Circumstances and Social Support.

This study investigates whether there are differences in quality of life-i.e., psychosomatic complaints and life satisfaction-between schoolchildren with and without a chronically ill or disabled parent at home.

Older Adults' Engagement in Residential Care: Pitfalls, Potentials, and the Role of ICTs.

Over the previous years, the residential care sector has gone through a transition from a rather paternalistic approach towards a more democratic way of caregiving. Nevertheless, many care organizations still find it challenging to engage their residents in the process of care. In this study, we investigated the challenges regarding the engagement of older adults in residential care.

Ion Homeostasis and Metabolome Analysis of 14-3-3 Quadruple Mutants to Salt Stress.

Salinity is one of the major abiotic stresses that limits agricultural productivity worldwide. Many proteins with defined functions in salt stress adaptation are controlled through interactions with members of the 14-3-3 family. In the present study, we generated three 14-3-3 quadruple knockout mutants (qKOs: , and ) to study the role of six non-epsilon group 14-3-3 proteins for salt stress adaptation.

Physiological and interactomic analysis reveals versatile functions of Arabidopsis 14-3-3 quadruple mutants in response to Fe deficiency.

To date, few phenotypes have been described for Arabidopsis 14-3-3 mutants or the phenotypes showing the role of 14-3-3 in plant responding to abiotic stress. Although one member of the 14-3-3 protein family (14-3-3 omicron) was shown to be involved in the proper operation of Fe acquisition mechanisms at physiological and gene expression levels in Arabidopsis thaliana, it remains to be explored whether other members play a role in regulating iron acquisition. To more directly and effectively observe whether members of 14-3-3 non-epsilon group have a function in Fe-deficiency adaptation, three higher order quadruple KOs, kappa/lambda/phi/chi (klpc), kappa/lambda/upsilon/nu(klun), and upsilon/nu/phi/chi (unpc) were generated and studied for physiological analysis in this study.

Pulmonary immunization: deposition site is of minor relevance for influenza vaccination but deep lung deposition is crucial for hepatitis B vaccination.

Vaccination the pulmonary route could be an attractive alternative to parenteral administration. Research towards the best site of antigen deposition within the lungs to induce optimal immune responses has conflicting results which might be dependent on the type of vaccine and/or its physical state. Therefore, in this study, we explored whether deep lung deposition is crucial for two different vaccines, .

Home care for terminally ill patients: the experiences of family caregivers with and without paid work.

Objectives: To facilitate care at the end of life at home, support from family caregivers is crucial. A substantial number of these family caregivers also work. Work in relation to care for terminally ill patients has received limited attention.

How Is End-of-Life Care With and Without Dementia Associated With Informal Caregivers' Outcomes?

Background: Palliative care for older people with life-limiting diseases often involves informal caregivers, but the palliative care literature seldom focuses on the negative and positive aspects of informal caregiving.

Objective: To assess the association of proximity to end of life (EOL) and dementia caregiving with informal caregivers' burden of care and positive experiences and explain differences in outcomes.

Design: Data on 1267 informal caregivers of community-dwelling older people were selected from a nationally representative cross-sectional survey and analyzed using analysis of variance and multivariable regression analyses.

Analysis of Arabidopsis thaliana HKT1 and Eutrema salsugineum/botschantzevii HKT1;2 Promoters in Response to Salt Stress in Athkt1:1 Mutant.

Soil salinity imposes a serious threat to the productivity of agricultural crops. Among several other transporters, high-affinity K transporter (HKT)'s play an important role in reducing the phytotoxicity of Na. Expression of Eutrema salsugineum (a halophyte) HKT1;2 is induced upon salt exposure.

Challenges for pulmonary delivery of high powder doses.

In recent years there is an increasing interest in the pulmonary delivery of large cohesive powder doses, i.e. drugs with a low potency such as antibiotics or drugs with a high potency that need a substantial fraction of excipient(s) such as vaccines stabilized in sugar glasses.

Salinity Tolerance of Two Potato Cultivars () Correlates With Differences in Vacuolar Transport Activity.

Potato is an important cultivated crop species and since it is moderately salt sensitive there is a need to develop more salt tolerant cultivars. A high activity of Na transport across the tonoplast in exchange for H is essential to reduce Na toxicity. The proton motive force (PMF) generated by the V-H-ATPase and the V-H-PPase energizes the Na(K)/H antiport.

The Arabidopsis GORK K-channel is phosphorylated by calcium-dependent protein kinase 21 (CPK21), which in turn is activated by 14-3-3 proteins.

Potassium (K) is a vital ion for many processes in the plant and fine-tuned ion channels control the K-fluxes across the plasma membrane. GORK is an outward-rectifying K-channel with important functions in stomatal closure and in root K-homeostasis. In this study, post-translational modification of the Arabidopsis GORK ion channel and its regulation by 14-3-3 proteins was investigated.

Synthesis and Characterization of a Bidirectional Photoswitchable Antagonist Toolbox for Real-Time GPCR Photopharmacology.

Noninvasive methods to modulate G protein-coupled receptors (GPCRs) with temporal and spatial precision are in great demand. Photopharmacology uses photons to control in situ the biological properties of photoswitchable small-molecule ligands, which bodes well for chemical biological precision approaches. Integrating the light-switchable configurational properties of an azobenzene into the ligand core, we developed a bidirectional antagonist toolbox for an archetypical family A GPCR, the histamine H receptor (HR).

Targeting the small airways with dry powder adenosine: a challenging concept.

: Small-particle inhaled corticosteroids (ICS) provide a higher small airway deposition than large-particle ICS. However, we are still not able to identify asthma patients who will profit most from small-particle treatment. : We aimed to identify these patients by selectively challenging the small and large airways.

Prerequisites for a dry powder inhaler for children with cystic fibrosis.

Correct inhalation technique is essential for effective use of dry powder inhalers (DPIs), as their effectiveness largely depends on the patient's inhalation manoeuvre. Children are an especially challenging target population for DPI development due to the large variability in understanding and inspiratory capacities. We previously performed a study in which we determined the prerequisites for a paediatric DPI in a mostly healthy paediatric population, for which we used an empty test inhaler with variable internal airflow resistance and mouthpiece.

Cold stress increases salt tolerance of the extremophytes Eutrema salsugineum (Thellungiella salsuginea) and Eutrema (Thellungiella) botschantzevii.

A comparative study was performed to analyze the effect of cold acclimation on improving the resistance of Arabidopsis thaliana, Eutrema salsugineum and Eutrema botschantzevii plants to salt stress. Shoot FW, sodium and potassium accumulation, metabolite content, expression of proton pump genes VAB1, VAB2,VAB3, VP2, HA3 and genes encoding ion transporters SOS1, HKT1, NHX1, NHX2, NHX5 located in the plasma membrane or tonoplast were determined just after the cold treatment and the onset of the salt stress. In the same cold-acclimated E.

Dry powder inhalation: past, present and future.

Early dry powder inhalers (DPIs) were designed for low drug doses in asthma and COPD therapy. Nearly all concepts contained carrier-based formulations and lacked efficient dispersion principles. Therefore, particle engineering and powder processing are increasingly applied to achieve acceptable lung deposition with these poorly designed inhalers.