Assisting the implementation of screening for type 1 diabetes by using artificial intelligence on publicly available data.

The type 1 diabetes community is coalescing around the benefits and advantages of early screening for disease risk. To be accepted by healthcare providers, regulatory authorities and payers, screening programmes need to show that the testing variables allow accurate risk prediction and that individualised risk-informed monitoring plans are established, as well as operational feasibility, cost-effectiveness and acceptance at population level. Artificial intelligence (AI) has the potential to contribute to solving these issues, starting with the identification and stratification of at-risk individuals.

Should Tinnitus Patients with Subclinical Hearing Impairment Be Offered Hearing Aids? A Comparison of Tinnitus Mitigation Following 3 Months Hearing Aid Use in Individuals with and without Clinical Hearing Impairment.

There is a consensus among tinnitus experts to not recommend hearing aids for tinnitus patients with subclinical hearing impairment. However, this notion is arbitrary, as no previous study has compared the treatment effect of hearing aids on tinnitus distress in patients with and without clinical hearing impairment. In this article, we investigate whether tinnitus patients with clinical and subclinical hearing impairment differ in terms of tinnitus mitigation after hearing aid fitting.

Structural and functional insights into the Pseudomonas aeruginosa glycosyltransferase WaaG and the implications for lipopolysaccharide biosynthesis.

The glycosyltransferase WaaG in Pseudomonas aeruginosa (PaWaaG) is involved in the synthesis of the core region of lipopolysaccharides. It is a promising target for developing adjuvants that could help in the uptake of antibiotics. Herein, we have determined structures of PaWaaG in complex with the nucleotide-sugars UDP-glucose, UDP-galactose, and UDP-GalNAc.

Lipid- and substrate-induced conformational and dynamic changes in a glycosyltransferase involved in E. coli LPS synthesis revealed by F and P NMR.

WaaG is a glycosyltransferase (GT) involved in the synthesis of the bacterial cell wall, and in Escherichia coli it catalyzes the transfer of a glucose moiety from the donor substrate UDP-glucose onto the nascent lipopolysaccharide (LPS) molecule which when completed constitutes the major component of the bacterium's outermost defenses. Similar to other GTs of the GT-B fold, having two Rossman-like domains connected by a short linker, WaaG is believed to undergo complex inter-domain motions as part of its function to accommodate the nascent LPS and UDP-glucose in the catalytic site located in the cleft between the two domains. As the nascent LPS is bulky and membrane-bound, WaaG is a peripheral membrane protein, adding to the complexity of studying the enzyme in a biologically relevant environment.

Dilute Bicelles for Glycosyltransferase Studies, Novel Bicelles with Phosphatidylinositol.

Solution-state NMR can be used to study protein-lipid interactions, in particular, the effect that proteins have on lipids. One drawback is that only small assemblies can be studied, and therefore, fast-tumbling bicelles are commonly used. Bicelles contain a lipid bilayer that is solubilized by detergents.

Work, family life and recovery: An exploratory study of "the third shift".

Background: Using 24-hour narratives as a starting-point, the present study examines conditions for recovery from work. The third shift concept forms the explorative starting point for highlighting the interplay between work, family responsibilities, leisure time and recovery.

Objective: The aim of the study is to explore how the third shift affects possibilities for recovery.

NMR structural analysis of the yeast cytochrome c oxidase subunit Cox13 and its interaction with ATP.

Background: Mitochondrial respiration is organized in a series of enzyme complexes in turn forming dynamic supercomplexes. In Saccharomyces cerevisiae (baker's yeast), Cox13 (CoxVIa in mammals) is a conserved peripheral subunit of Complex IV (cytochrome c oxidase, CytcO), localized at the interface of dimeric bovine CytcO, which has been implicated in the regulation of the complex.

Results: Here, we report the solution NMR structure of Cox13, which forms a dimer in detergent micelles.

Simulated basis sets for semi-LASER: the impact of including shaped RF pulses and magnetic field gradients.

Objective: To study the need for inclusion of shaped RF pulses and magnetic field gradients in simulations of basis sets for the analysis of proton MR spectra of single voxels of the brain acquired with a semi-LASER pulse sequence.

Materials And Methods: MRS basis sets where simulated at different echo times with hard RF pulses as well as with shaped RF pulses without or with magnetic field gradients included. The influence on metabolite concentration quantification was assessed using both phantom and in vivo measurements.

Soluble TatA forms oligomers that interact with membranes: Structure and insertion studies of a versatile protein transporter.

The twin-arginine translocase (Tat) mediates the transport of already-folded proteins across membranes in bacteria, plants and archaea. TatA is a small, dynamic subunit of the Tat-system that is believed to be the active component during target protein translocation. TatA is foremost characterized as a bitopic membrane protein, but has also been found to partition into a soluble, oligomeric structure of yet unknown function.

NMR Structure and Dynamics Studies of Yeast Respiratory Supercomplex Factor 2.

The Saccharomyces cerevisiae respiratory supercomplex factor 2 (Rcf2) is a 224-residue protein located in the mitochondrial inner membrane where it is involved in the formation of supercomplexes composed of cytochrome bc and cytochrome c oxidase. We previously demonstrated that Rcf2 forms a dimer in dodecylphosphocholine micelles, and here we report the solution NMR structure of this Rcf2 dimer. Each Rcf2 monomer has two soluble α helices and five putative transmembrane (TM) α helices, including an unexpectedly charged TM helix at the C terminus, which mediates dimer formation.

The identification of adverse events in hip fracture patients using the Global Trigger Tool: A prospective observational cohort study.

Introduction: Hip fracture is common in the elderly and is associated with high comorbidity, mortality and complication rates. There has been an increase in the investigation of healthcare-related adverse events (AEs) in some patient groups but there is limited knowledge about hip fracture patients. The aim was to explore the incidence, preventability and nature of AEs in hip fracture patients.

Correlations between the structure and the vibrational spectrum of the phosphate group. Implications for the analysis of an important functional group in phosphoproteins.

Density functional theory calculations were used to establish correlations between the structure and the vibrational spectrum of the phosphate group in model compounds for phosphorylated amino acids. The model compounds were acetyl phosphate, methyl phosphate, and -tolyl phosphate, which represented the phosphorylated amino acids aspartyl phosphate, serine or threonine phosphate, and tyrosine phosphate, respectively. The compounds were placed in different environments consisting of one or several HF or HO molecules, which modeled interactions of phosphorylated amino acids in the protein environment.

Workplace relationships impact self-rated health: A survey of Swedish municipal health care employees.

Background: The impact of positive social relationships on the health of municipal employees in the elder care sector in Sweden needs further examination.

Objective: To explore the association between health and relationships among elderly care employees using a salutogenic perspective.

Method: Survey of all employees (n = 997) in special housing, home care and Disabled Support and Services in a Swedish municipality.

Resources for work-related well-being: A qualitative study about healthcare employees' experiences of relationships at work.

Aims And Objectives: To explore municipal healthcare employees' experiences of relationships with care recipients and colleagues. The specific research questions were when do the relationships enhance well-being, and what prerequisites are needed for such relationships to occur?

Background: Employees in health and social care for older people often depict their work in negative terms, and they often take a high number of sick leaves. Despite the heavy workload, other employees express well-being at work and highlight social relationships as one reason for this.

Structure and dynamics of plant TatA in micelles and lipid bilayers studied by solution NMR.

The twin-arginine translocase (Tat) transports folded proteins across the cytoplasmic membrane of prokaryotes and the thylakoid membrane of plant chloroplasts. In Gram-negative bacteria and chloroplasts, the translocon consists of three subunits, TatA, TatB, and TatC, of which TatA is responsible for the actual membrane translocation of the substrate. Herein we report on the structure, dynamics, and lipid interactions of a fully functional C-terminally truncated 'core TatA' from Arabidopsis thaliana using solution-state NMR.

Solution NMR structure of yeast Rcf1, a protein involved in respiratory supercomplex formation.

The respiratory supercomplex factor 1 (Rcf1) protein is located in the mitochondrial inner membrane where it is involved in formation of supercomplexes composed of respiratory complexes III and IV. We report the solution structure of Rcf1, which forms a dimer in dodecylphosphocholine (DPC) micelles, where each monomer consists of a bundle of five transmembrane (TM) helices and a short flexible soluble helix (SH). Three TM helices are unusually charged and provide the dimerization interface consisting of 10 putative salt bridges, defining a "charge zipper" motif.

NMR Study of Rcf2 Reveals an Unusual Dimeric Topology in Detergent Micelles.

The Saccharomyces cerevisiae mitochondrial respiratory supercomplex factor 2 (Rcf2) plays a role in assembly of supercomplexes composed of cytochrome bc (complex III) and cytochrome c oxidase (complex IV). We expressed the Rcf2 protein in Escherichia coli, refolded it, and reconstituted it into dodecylphosphocholine (DPC) micelles. The structural properties of Rcf2 were studied by solution NMR, and near complete backbone assignment of Rcf2 was achieved.

Fast-tumbling bicelles constructed from native Escherichia coli lipids.

Solution-state NMR requires small membrane mimetic systems to allow for acquiring high-resolution data. At the same time these mimetics should faithfully mimic biological membranes. Here we characterized two novel fast-tumbling bicelle systems with lipids from two Escherichia coli strains.

Membrane Interaction of the Glycosyltransferase WaaG.

The glycosyltransferase WaaG is involved in the synthesis of lipopolysaccharides that constitute the outer leaflet of the outer membrane in Gram-negative bacteria such as Escherichia coli. WaaG has been identified as a potential antibiotic target, and inhibitor scaffolds have previously been investigated. WaaG is located at the cytosolic side of the inner membrane, where the enzyme catalyzes the transfer of the first outer-core glucose to the inner core of nascent lipopolysaccharides.

Comparable mRNA expression of inflammatory markers but lower claudin-1 mRNA levels in foreskin tissue of HSV-2 seropositive versus seronegative asymptomatic Kenyan young men.

Objectives: Skin biopsies from local sites of herpes simplex virus 2 (HSV-2)-induced ulcers can show infiltrates of inflammatory cells several months after macroscopic healing. We hypothesise that foreskin tissue samples of asymptomatic HSV-2 seropositive men had remaining signs of inflammation at the molecular level. Even in the absence of clinical lesions, genital inflammation may contribute to increased HIV susceptibility on sexual exposure to the virus.

Blockade of type I interferon (IFN) production by retroviral replicating vectors and reduced tumor cell responses to IFN likely contribute to tumor selectivity.

Unlabelled: We developed a Moloney mouse leukemia virus (MLV)-based retroviral replicating vector (RRV), Toca 511, which has displayed tumor specificity in resected brain tumor material and blood in clinical trials. Here, we investigated the interaction between Toca 511 and human host cells, and we show that RRVs do not induce type I interferon (IFN) responses in cultured human tumor cells or cultured human primary cells. However, exogenous type I IFN inhibited RRV replication in tumor cells and induced IFN-regulated genes, albeit at a lower level than in primary cells.

Maintaining therapeutic activity in the operating room: compatibility of a gamma-retroviral replicating vector with clinical materials and biofluids.

Toca 511 is a novel retroviral replicating vector, encoding a modified yeast cytosine deaminase, administered to recurrent high grade glioma patients in Phase 1 trials by stereotactic, transcranial injection into the tumor or into the walls of the resection cavity. A key issue, with little published data, is vector biocompatibility with agents likely to be encountered in a neurosurgical setting. We tested biocompatibility of Toca 511 with: delivery devices; MRI contrast agents, including ProHance supporting coinjection for real time MRI-guided intratumoral delivery; hemostatic agents; biofluids (blood and cerebrospinal fluid); potential adjuvants; and a needleless vial adapter that reduces risk of accidental needle sticks.

A 5-year retrospective study on Replace Select Tapered dental implants.

Background: Long-term data regarding survival and crestal bone loss for Replace Select Tapered implants (Nobel Biocare AB, Gothenburg, Sweden) are lacking.

Purpose: The study aims to present the 5-year outcomes from a retrospective analysis of Replace Select Tapered implants placed and restored in consecutive patients.

Materials And Methods: A total of 88 consecutive patients (32 male, 56 female, mean age 65 ± 12 years) treated by one clinician (PP) were clinically and radiographically evaluated during at least 5 years of function.

Production of unique immunotoxin cancer therapeutics in algal chloroplasts.

The idea of targeted therapy, whereby drug or protein molecules are delivered to specific cells, is a compelling approach to treating disease. Immunotoxins are one such targeted therapeutic, consisting of an antibody domain for binding target cells and molecules of a toxin that inhibits the proliferation of the targeted cell. One major hurdle preventing these therapies from reaching the market has been the lack of a suitable production platform that allows the cost-effective production of these highly complex molecules.