Improving the sustainability of biopharmaceutical downstream processing through buffer recycling.

The production of biopharmaceuticals is a chemical- and water-intensive process. The consumption of water and chemicals is partly due to the need for many different buffers in large volumes during the downstream process, typically consisting of several chromatography steps. Given the global commitment to the goals for sustainable development and the anticipated growth of the biopharmaceutical market, the consumption of large buffer volumes is expected to become problematic.

Representations of professional nursing homes in the context of climate-related heatwaves: An exploratory study of Swedish media.

In recent years, a relatively large number of articles in the Swedish media have reported on the problems that afflict nursing homes due to prolonged and climate-related heatwaves during the summer months. Older residents are badly affected by the heat, especially as many nursing homes in Sweden lack air conditioning. This paper aims to explore how nursing homes are depicted in the Swedish press in relation to climate-related heatwaves, professional care, and risk management.

Experiences and actions of part-time firefighters' family members: a critical incident study.

Objectives: The purpose of this study was to describe the experiences and actions of part-time firefighters' family members in rural areas in Sweden.

Design: The study had an inductive descriptive design and used the critical incident technique.

Setting: Rural areas, primarily served by a part-time fire station, across Sweden.

Mosaic chromosomal alterations in hematopoietic cells and clinical outcomes in patients with multiple myeloma.

Mosaic chromosomal alterations (mCAs) in hematopoietic cells increase mortality and risk of hematological cancers and infections. We investigated the landscape of mCAs and their clinical consequences in 976 patients with multiple myeloma undergoing high-dose chemotherapy and autologous stem cell support (ASCT) with median 6.4 years of follow-up.

Positive Allosteric Modulators of Trk Receptors for the Treatment of Alzheimer's Disease.

Neurotrophins are important regulators of neuronal and non-neuronal functions. As such, the neurotrophins and their receptors, the tropomyosin receptor kinase (Trk) family of receptor tyrosine kinases, has attracted intense research interest and their role in multiple diseases including Alzheimer's disease has been described. Attempts to administer neurotrophins to patients have been reported, but the clinical trials have so far have been hampered by side effects or a lack of clear efficacy.

Pore Formation by Amyloid-like Peptides: Effects of the Nonpolar-Polar Sequence Pattern.

One of the mechanisms accounting for the toxicity of amyloid peptides in diseases like Alzheimer's and Parkinson's is the formation of pores on the plasma membrane of neurons. Here, we perform unbiased all-atom simulations of the full membrane damaging pathway, which includes adsorption, aggregation, and perforation of the lipid bilayer accounting for pore-like structures. Simulations are performed using four peptides made with the same amino acids.

Health literacy in patients participating in cardiac rehabilitation: A prospective cohort study with pre-post-test design.

Background And Aims: Adherence to recommendations regarding medical treatment and healthy behaviour serve as a significant challenge for patients experiencing a cardiac event. Optimizing the patients' health literacy (HL) may be crucial to meet this challenge and has gained increased focus the last decade. Despite cardiac rehabilitation (CR) being a central part of the treatment of patients experiencing a cardiac event, such programs have not been evaluated regarding HL.

Hybrid Amyloid Quantum Dot Nano-Bio Assemblies to Probe Neuroinflammatory Damage.

Various oligomeric species of amyloid-beta have been proposed to play different immunogenic roles in the cellular pathology of Alzheimer's Disease. The dynamic interconversion between various amyloid oligomers and fibrillar assemblies makes it difficult to elucidate the role each potential aggregation state may play in driving neuroinflammatory and neurodegenerative pathology. The ability to identify the amyloid species that are key and essential drivers of these pathological hallmarks of Alzheimer's Disease is of fundamental importance for also understanding downstream events including tauopathies that mediate neuroinflammation with neurologic deficits.

Visualization and characterization of complement activation in acetylcholine receptor antibody seropositive myasthenia gravis.

Introduction/aims: There are no blood biomarkers to monitor treatment effects in myasthenia gravis (MG) or studies visualizing the acetylcholine receptor (AChR) antibody-induced membrane attack complex (MAC) at the human muscle membrane. This study aimed to compare levels of complement activation products and native complement components in MG patients and healthy controls (HCs) and to model the AChR antibody-mediated attacks in human muscle cells.

Methods: We assessed the complement components and activation product levels with enzyme-linked immunosorbent assay and magnetic bead-based sandwich assays in plasma and sera of 23 MG patients and matched HCs.

An exploratory study of the damage markers NfL, GFAP, and t-Tau, in cerebrospinal fluid and other findings from a patient cohort enriched for suspected autoimmune psychiatric disease.

There is growing evidence suggesting that immunological mechanisms play a significant role in the development of psychiatric symptoms in certain patient subgroups. However, the relationship between clinical red flags for suspected autoimmune psychiatric disease and signs of central nervous system (CNS) pathology (e.g.

Real-time monitoring of gradient chromatography using dual Kalman-filters.

Real-time state estimation in chromatography is a useful tool to improve monitoring of biopharmaceutical downstream processes, combining mechanistic model predictions with real-time data acquisition to obtain an estimation that surpasses that of either approach individually. One common technique for real-time state estimation is Kalman filtering. However, non-linear adsorption isotherms pose a significant challenge to Kalman filters, which are dependent on fast algorithm execution to function.

Stent coating containing a charged silane coupling agent that regulates protein adsorption to confer antithrombotic and cell-adhesion properties.

The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available.

Vitamin D triggers hCAP18/LL-37 production: Implications for LL-37-induced human osteoblast cytotoxicity.

The human cathelicidin LL-37 shows activity against microorganisms, but it is also cytotoxic to host cells. The CAMP gene codes for the LL-37 precursor hCAP18 which is processed extracellularly to active LL-37. It has previously been shown that vitamin D stimulates CAMP gene activity, but less information is available demonstrating that vitamin D also can increase hCAP18/LL-37 protein production.

Voluntary first responders' experiences of being dispatched to suspected out-of-hospital cardiac arrest in rural areas: an interview study.

Background: Out-of-hospital cardiac arrest (OHCA) is a leading cause of death, and survival outcomes vary across countries and regions. To improve survival, the European Resuscitation Council Guidelines encourage the implementation of technologies like smartphone applications to alert voluntary first responders (VFRs) who are near a suspected OHCA. VFRs are of great importance in the ´chain of survival´, but there is still a lack of knowledge about their experiences; especially of those operating in rural areas.

Automatic procedure for modelling, calibration, and optimization of a three-component chromatographic separation.

The current landscape of biopharmaceutical production necessitates an ever-growing set of tools to meet the demands for shorter development times and lower production costs. One path towards meeting these demands is the implementation of digital tools in the development stages. Mathematical modelling of process chromatography, one of the key unit operations in the biopharmaceutical downstream process, is one such tool.

Peptide Self-Assembly into Amyloid Fibrils: Unbiased All-Atom Simulations.

Protein self-assembly plays an important role in biological systems, accounting for the formation of mesoscopic structures that can be highly symmetric as in the capsid of viruses or disordered as in molecular condensates or exhibit a one-dimensional fibrillar morphology as in amyloid fibrils. Deposits of the latter in tissues of individuals with degenerative diseases like Alzheimer's and Parkinson's has motivated extensive efforts to understand the sequence of molecular events accounting for their formation. These studies aim to identify on-pathway intermediates that may be the targets for therapeutic intervention.

ACD856, a novel positive allosteric modulator of Trk receptors, single ascending doses in healthy subjects: Safety and pharmacokinetics.

Purpose: AlzeCure Pharma AB is developing novel positive allosteric modulators of Trk-receptors for treatment of Alzheimer's disease, depression, other psychiatric conditions and other disorders where cognition is impaired. The preceding candidate drug ACD855 was shown to have a too long half-life in humans to allow further development. To de-risk the development of the follow-up compound ACD856, the oral single ascending dose study of ACD856 in humans was preceded by an intravenous microdose study, assessing the elimination half-life in plasma.

Response times in rural areas for emergency medical services, fire and rescue services and voluntary first responders during out-of-hospital cardiac arrests.

Aim: To increase survival in out-of-hospital cardiac arrests (OHCA), great efforts are made to improve the number of voluntary first responders (VFR). However, evidence of the potential utility of such efforts is sparse, especially in rural areas. Therefore, the aim was to describe and compare response times for emergency medical services (EMS), fire and rescue services (FRS), and VFR during OHCA in relation to population density.

Prompt Thrombo-Inflammatory Response to Ischemia-Reperfusion Injury and Kidney Transplant Outcomes.

Introduction: In kidney transplantation (KT), the role of the intravascular innate immune system (IIIS) in response to ischemia-reperfusion injury (IRI) is not well-understood. Here, we studied parallel changes in the generation of key activation products of the proteolytic cascade systems of the IIIS following living donor (LD) and deceased donor (DD) transplantation and evaluated potential associations with clinical outcomes.

Methods: In a cohort study, 63 patients undergoing LD ( = 26) and DD ( = 37) transplantation were prospectively included.