Introduction: When older persons with dementia are admitted to hospital, they often feel disoriented and confused and their cognitive impairment may worsen, purely due to the sudden change in their environment. As such hospital design is recognised as an important aspect in the care and well-being of older persons with dementia. As the number of persons with dementia is increasing, the experience of admission to a hospital with, for example, single rooms is more relevant than ever.
View Article and Find Full Text PDFNucleic Acids Res
October 2023
Implementation of therapeutic in vivo gene editing using CRISPR/Cas relies on potent delivery of gene editing tools. Administration of ribonucleoprotein (RNP) complexes consisting of Cas protein and single guide RNA (sgRNA) offers short-lived editing activity and safety advantages over conventional viral and non-viral gene and RNA delivery approaches. By engineering lentivirus-derived nanoparticles (LVNPs) to facilitate RNP delivery, we demonstrate effective administration of SpCas9 as well as SpCas9-derived base and prime editors (BE/PE) leading to gene editing in recipient cells.
View Article and Find Full Text PDFThe frontline therapy R-CHOP for patients with diffuse large B-cell lymphoma (DLBCL) has remained unchanged for two decades despite numerous Phase III clinical trials investigating new alternatives. Multiple large studies have uncovered genetic subtypes of DLBCL enabling a targeted approach. To further pave the way for precision oncology, we perform genome-wide CRISPR screening to uncover the cellular response to one of the components of R-CHOP, vincristine, in the DLBCL cell line SU-DHL-5.
View Article and Find Full Text PDFLocus-directed DNA cleavage induced by the CRISPR-Cas9 system triggers DNA repair mechanisms allowing gene repair or targeted insertion of foreign DNA. For gene insertion to be successful, availability of a homologous donor template needs to be timed with cleavage of the DNA by the Cas9 endonuclease guided by a target-specific single guide RNA (sgRNA). We present a novel approach for targeted gene insertion based on a single integrase-defective lentiviral vector (IDLV) carrying a Cas9 off switch.
View Article and Find Full Text PDFWe observe monopole oscillations in a mixture of Bose-Einstein condensates, where the usually dominant mean-field interactions are canceled. In this case, the system is governed by the next-order Lee-Huang-Yang (LHY) correction to the ground state energy, which describes the effect of quantum fluctuations. Experimentally such a LHY fluid is realized by controlling the atom numbers and interaction strengths in a ^{39}K spin mixture confined in a spherical trap potential.
View Article and Find Full Text PDFIntroduction: Actinic keratosis (AK) is a skin condition arising from chronic exposure to ultraviolet light and may lead to the development of malignancies. This trial aimed to evaluate efficacy and safety of ingenol disoxate gel (IngDsx, 0.018% for face/chest [FC]; 0.
View Article and Find Full Text PDFReal-time monitoring of bioprocesses plays a key-role in modern industries, providing new information on full-scale production, thus enabling control of the process and allowing it to run at optimal conditions while minimizing waste. Monitoring of phosphates and ammonium in fermentation processes has a twofold interest: they are important nutrients for living organisms while at the same time constituting environmental nutrient pollutants, for which unnecessary use and disposal must be avoided. In this report, the possibility of simultaneous analysis of phosphates and ammonium in fermentations was verified using spectroscopy-based methods combined with chemometrics to construct calibration models.
View Article and Find Full Text PDFLittle is known about prevalence of PD-L1 expression in tumor cells of unselected patients with all stages of non-small cell lung cancer. The objective of this study is to assess the prevalence of PD-L1 positivity in patients with non-small cell lung cancer, to analyze the association between PD-L1 positivity and patients' clinicopathological characteristics, and to assess the use of immune-oncologic treatment in eligible patients. All non-small cell lung cancer patients diagnosed in a 10-month period in an unselected population of 1.
View Article and Find Full Text PDFBackground: Ingenol mebutate (IngMeb) 0.015% or 0.05% is approved for actinic keratosis (AK) areas of 25 cm or less; some patients require treatment of larger fields.
View Article and Find Full Text PDFThe ever-growing competition among global biotech industries has led to high demands on production consistency. A statistical strategy of performance mapping for production optimization is therefore of great economic significance. Process analytical technology (PAT)-based sensors such as mid-infrared (MIR) spectroscopy enable process monitoring through substrate and by-product concentrations that directly represent the physiology of cells.
View Article and Find Full Text PDFDifferent opportunities are explored to evaluate quality variation in raw materials from biological origin. Assessment of raw materials attributes is an important step in a bio-based production as fluctuations in quality are a major source of process disturbance. This can be due to a variety of biological, seasonal, and supply scarcity reasons.
View Article and Find Full Text PDFAim: Necrotising enterocolitis (NEC) is often staged according to Bell's 1978 system, but today's NEC cases are more immature than the ones that were used to develop Bell's stages. Our aim was to explore the clinical and radiographic findings of contemporary cases of NEC and spontaneous intestinal perforation.
Methods: We coded the clinical records of all cases of NEC stages I-III and spontaneous intestinal perforation born in 2006-2015 at the tertiary department of neonatology at Rigshospitalet, Denmark, for 16 clinical and radiographic symptoms and signs at disease onset and at climax.
Introduction: Actinic keratosis is regarded as a chronic disease of the skin and, although fluctuating, is chronically progressive. Approval of new products for the treatment of actinic keratosis requires the use of a standard methodology in clinical trials which emphasize complete clearance of all actinic keratoses in a treatment field in a defined time span and the evaluation of long-term efficacy in terms of recurrence rate among completely cleared patients.
Methods: Analysis of data from six previously published clinical trials in patients with actinic keratosis.
Background And Objectives: Ingenol disoxate (LEO 43204) is a field therapy in development for the treatment of actinic keratosis (AK) on areas between 25 and 250 cm. We evaluated the systemic exposure and safety of ingenol disoxate under maximum-use conditions.
Methods: This was a phase I, open-label, non-randomized, multicenter trial.
Protein hydrolysates are of great interest in the food industry due to their nutritional and functional properties, but their use often implies solubilization in water and therefore hamper the use of plant proteins with inherent low water solubility. Protein solubility in water can be modified by enzymatic hydrolysis, but during this process several collateral properties of the protein hydrolysates changes. It is therefore important to determine the end-point of the process and to monitor its development.
View Article and Find Full Text PDFIn this study, the aim was to establish if loss of DNA integrity is a cause of loss of culturability for probiotic bacteria during storage in dry state. The number of colony forming units (CFU), number of metabolically active cells, and DNA integrity during dry storage of probiotic strains, B. animalis subsp.
View Article and Find Full Text PDFAn industrial scale biomass production using batch or fed-batch fermentations usually optimized by selection of bacterial strains, tuning fermentation media, feeding strategy, and temperature. However, in-depth investigation of the biomass metabolome during the production may reveal new knowledge for better optimization. In this study, for the first time, the authors investigated seven fermentation batches performed on five Streptoccoccus thermophilus strains during the biomass production at Chr.
View Article and Find Full Text PDFBackground: Ingenol mebutate (IngMeb) and diclofenac sodium (DS) are approved treatments for actinic keratosis (AK).
Objectives: To compare the efficacy and safety of IngMeb 0·015% gel with DS 3% gel (NCT02406014).
Methods: Patients with 4-8 visible, discrete AK lesions on the face/scalp in a 25 cm contiguous area of skin were randomized 1:1 to IngMeb once-daily for three consecutive days or DS twice-daily for 90 days.
Scope: The aim of the paper is to investigate whether changes in the metabolome could explain observed changes in body composition in overweight adults after consumption of butter with high level of medium-chain fatty acids (MCFAs) in combination with casein or whey.
Methods And Results: With GC-TOF and LC-Q/MS, metabolites in plasma and urine from a 12-week randomized double-blinded human intervention including 52-abdominally overweight adults were analyzed. The participants consumed 63 g per day of milk fat (high or low in MCFAs) and 60 g per day of protein (whey or casein).
Background: Actinic keratosis (AK) can affect large skin areas. Ingenol mebutate (IngMeb) gel (0.015% and 0.
View Article and Find Full Text PDFBackground: Programmed cell death ligand-1 (PD-L1) expression is a predictive biomarker for anti-PD-1 immunotherapy in non-small cell lung cancer. Different immunohistochemistry (IHC) assays have been developed on histologic material with different cutoffs for positivity. More than one third of the patients are diagnosed on cytology alone.
View Article and Find Full Text PDFIngenol mebutate gel, a topical field treatment for actinic keratosis (AK), elicits inflammatory application-site reactions in most patients. This analysis explored the relationship between the intensity of local skin reactions (LSRs) and AK clearance, measured by the reduction in AK count from baseline in 218 patients who were treated for AK on the face in the pivotal Phase 3 studies. The analysis modeled the AK count at week 8, adjusted for baseline count, with the composite LSR score at 1 day after the last treatment application for each patient as a predictor to estimate the mean and 90% prediction interval for the percent reduction in AK count.
View Article and Find Full Text PDFIngenol mebutate represents a topical treatment for fields with actinic keratosis (AK). The biological effects of ingenol mebutate in AK, subclinical (SC)-AK, and reference-skin were assessed and graded by in vivo reflectance confocal microscopy (RCM) and histology. Patients with AK and SC-AK lesions in one 25 cm2 field on hands or forearms, and with an area of reference skin on the inner upper arm, were included.
View Article and Find Full Text PDFBackground: Ingenol mebutate gel is a topical field treatment for actinic keratosis (AK). The treatment elicits application-site reactions in most patients. This analysis evaluated the relationship between the severity of reactions and the speed of their resolution.
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