Tethered Particle Motion Analysis of DNA-Binding Properties of Architectural Proteins.

Architectural DNA-binding proteins are key to the organization and compaction of genomic DNA inside cells. Tethered particle motion (TPM) permits analysis of DNA conformation and detection of changes in conformation induced by such proteins at the single molecule level in vitro. As many individual protein-DNA complexes can be investigated in parallel, these experiments have high throughput.

Quantitative Determination of DNA Bridging Efficiency of Chromatin Proteins.

DNA looping is important for genome organization in all domains of life. The basis of DNA loop formation is the bridging of two separate DNA double helices. Detecting DNA bridge formation generally involves the use of complex single-molecule techniques (atomic force microscopy, magnetic or optical tweezers).

Microscale Thermophoresis Analysis of Chromatin Interactions.

Architectural DNA-binding proteins are key to the organization and compaction of genomic DNA inside cells. The activity of architectural proteins is often subject to further modulation and regulation through the interaction with a diverse array of other protein factors. Detailed knowledge on the binding modes involved is crucial for our understanding of how these protein-protein and protein-DNA interactions shape the functional landscape of chromatin in all kingdoms of life: bacteria, archaea, and eukarya.

Recent trends in asthma diagnosis, preschool wheeze diagnosis and asthma exacerbations in English children and adolescents: a SABINA Jr study.

Background: Asthma-related burden remains poorly characterised in children in the UK. We quantified recent trends in asthma prevalence and burden in a UK population-based cohort (1‒17-year-olds).

Methods: The Clinical Practice Research Datalink Aurum database (2008‒2018) was used to assess annual asthma incidence and prevalence in 1‒17-year-olds and preschool wheeze in 1‒5-year-olds, stratified by sex and age.

Implementation of exergaming for people with dementia: facilitators, barriers, and recommendations.

Objectives: To identify facilitators, barriers, and formulate recommendations for the implementation of exergames for people with dementia (PWD) in day-care centers (DCCs).

Methods: Within a randomized controlled trial into the effectiveness of exergaming, 73 PWD with their informal caregivers (IC) from 11 DCCs in the Netherlands and two exergame providers participated in a process evaluation. This was a mixed-methods study using focus groups, semi-structured interviews, the Measurement Instrument for Determinants of Innovations, forms for DCC staff, and a short satisfaction questionnaire.

Specific DNA binding of archaeal histones HMfA and HMfB.

In archaea, histones play a role in genome compaction and are involved in transcription regulation. Whereas archaeal histones bind DNA without sequence specificity, they bind preferentially to DNA containing repeats of alternating A/T and G/C motifs. These motifs are also present on the artificial sequence "Clone20," a high-affinity model sequence for binding of the histones from .

Short-acting β-agonists and exacerbations in children with asthma in England: SABINA Junior.

Background: Prescription of three or more short-acting β-agonist (SABA) canisters per year in adult and adolescent asthma populations is associated with a risk of severe exacerbations; however, evidence in children aged <12 years is limited.

Methods: This study analysed data on children and adolescents with asthma in three age cohorts: 1‒5 years, 6‒11 years and 12‒17 years from the Clinical Practice Research Datalink Aurum database for the period 1 January 2007 to 31 December 2019. Associations between SABA prescriptions (three or more fewer than three canisters per year) at baseline, defined as 6 months after an asthma diagnosis as a binary exposure variable, and the rate of future asthma exacerbations, defined as oral corticosteroid burst therapy, an emergency department visit or hospital admission, were assessed by multilevel negative binomial regression, adjusted for relevant demographic and clinical confounders.

Health, Hope, and Harmony: A Systematic Review of the Determinants of Happiness across Cultures and Countries.

The aim of this study was to review the literature on what constitutes happiness across cultures and countries to advance scholarly knowledge on the happiness construct. A systematic review was conducted to examine the determinants of happiness in samples across cultures and countries. Five different databases, including APA PsycNet, EBSCO-Academic, EBSCO-Business, Project MUSE, and Google Scholar, grey literature, and in-text references from relevant review articles were used.

A comparison of the effectiveness of different doses of tocilizumab and sarilumab in the treatment of severe COVID-19: a natural experiment due to drug shortages.

Objectives: Interleukin (IL)-6 inhibitors are administered to treat patients hospitalized with COVID-19. In 2021, due to shortages, different dosing regimens of tocilizumab, and a switch to sarilumab, were consecutively implemented. Using real-world data, we compare the effectiveness of these IL-6 inhibitors.

[Medication waste in a hospital setting: concerns and considerations].

The use of medication contributes significantly to the total CO2 emission caused by the public health sector. Conservative estimates reveal that the amount of medication distributed by public pharmacies but is wasted unused equalizes a total amount of 100 million euro. Data regarding medication waste in hospitals is not yet available.

Short-acting β -agonist use and asthma exacerbations in Swedish children: A SABINA Junior study.

Background: In adults and adolescents with asthma, use of ≥3 short-acting β -agonist (SABA) canisters/year is associated with increased exacerbation risk. Whether this association is present in younger children remains unknown. In this SABA use IN Asthma (SABINA) Junior study, we assessed the association of SABA collection with exacerbation risk in the general Swedish pediatric asthma population.

Saturated fat: villain and bogeyman in the development of cardiovascular disease?

Aims: Cardiovascular disease (CVD) is the leading global cause of death. For decades, the conventional wisdom has been that the consumption of saturated fat (SFA) undermines cardiovascular health, clogs the arteries, increases risk of CVD, and leads to heart attacks. It is timely to investigate whether this claim holds up to scientific scrutiny.

Short-Acting Beta-2-Agonist Exposure and Severe Asthma Exacerbations: SABINA Findings From Europe and North America.

Background: Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting beta-2 agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists.

Objective: To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe.

Methods: Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 y) from Canada, France, the Netherlands, Poland, Spain, the United Kingdom, and the United States.

Reply to: Cause or consequence?

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Short-acting β-agonist prescriptions are associated with poor clinical outcomes of asthma: the multi-country, cross-sectional SABINA III study.

Background: To gain a global perspective on short-acting β-agonist (SABA) prescriptions and associated asthma-related clinical outcomes in patients with asthma, we assessed primary health data across 24 countries in five continents.

Methods: SABINA III was a cross-sectional study that employed electronic case report forms at a study visit (in primary or specialist care) to record prescribed medication(s), over-the-counter (OTC) SABA purchases and clinical outcomes in asthma patients (≥12 years old) during the past 12 months. In patients with ≥1 SABA prescriptions, associations of SABA with asthma symptom control and severe exacerbations were analysed using multivariable regression models.

Tessier 30 Facial Clefts-A Literature Review of 72 Cases (1996-2020), Suggested Treatment Protocol, Outcome Measures, Minimum Dataset for Future Case Reports, and Registries.

Introduction: Tessier 30 facial cleft is a rare anomaly presenting in the soft and hard tissues over the central lower face. Owing to the rarity of cases and difficulty of treatment, there is no universally accepted surgical management strategy. The last comprehensive literature review of Tessier 30 clefts was in 1996.

Mechanical and structural properties of archaeal hypernucleosomes.

Many archaea express histones, which organize the genome and play a key role in gene regulation. The structure and function of archaeal histone-DNA complexes remain however largely unclear. Recent studies show formation of hypernucleosomes consisting of DNA wrapped around an 'endless' histone-protein core.

Reconstitution and functional characterization of the FtsH protease in lipid nanodiscs.

FtsH is a membrane-bound protease that plays a crucial role in proteolytic regulation of many cellular functions. It is universally conserved in bacteria and responsible for the degradation of misfolded or misassembled proteins. A recent study has determined the structure of bacterial FtsH in detergent micelles.

The cytoplasmic domain of the AAA+ protease FtsH is tilted with respect to the membrane to facilitate substrate entry.

AAA+ proteases are degradation machines that use ATP hydrolysis to unfold protein substrates and translocate them through a central pore toward a degradation chamber. FtsH, a bacterial membrane-anchored AAA+ protease, plays a vital role in membrane protein quality control. How substrates reach the FtsH central pore is an open key question that is not resolved by the available atomic structures of cytoplasmic and periplasmic domains.

Asthma-Related Health Outcomes Associated with Short-Acting β-Agonist Inhaler Use: An Observational UK Study as Part of the SABINA Global Program.

Introduction: Patients with asthma typically increase short-acting β-agonists (SABA) use with worsening symptoms. Excessive SABA use may lead to a higher risk of adverse outcomes. We evaluated, in a large population cohort, an association between SABA inhaler use and asthma exacerbations and healthcare utilization.

Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial.

Background: Previous studies have highlighted a relationship between reduction in rate of exacerbations with therapies containing inhaled corticosteroids (ICS) and baseline blood eosinophil count in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial showed that once-daily single-inhaler triple therapy significantly reduced exacerbations versus dual therapies. Blood eosinophil counts and smoking status could be important modifiers of treatment response to ICS.

The (cost-) effectiveness of exergaming in people living with dementia and their informal caregivers: protocol for a randomized controlled trial.

Background: Physical activity is linked to benefits such as increased physical fitness, cognition, emotional and social functioning, general health and well-being in older people. Some evidence suggests that this also applies to people living with dementia. However, it can be harder for them to perform physical activities, due to several barriers, such as issues with orientation and balance problems.

Quantitative Determination of DNA Bridging Efficiency of Chromatin Proteins.

DNA looping is important for genome organization in all domains of life. The basis of DNA loop formation is the bridging of two separate DNA double helices. Detecting DNA bridge formation generally involves the use of complex single-molecule techniques (atomic force microscopy, magnetic, or optical tweezers).